Download GUIDELINES ON BLADDER CANCER Muscle invasive and

MVCN Urology NSSG
Clinical and Referral Guidelines
11-1A-205g; 11-1A-206g; 11-1A-207g;
11-1A-208g; 11-1A-209g; 11-1A-210g;
11-1A-211g; 11-1A-212g; 11-1A-213g;
Version number as approved and
0.5
published
Authors
Mr Jim Adshead
Mr Manoah Pancharatnam (Muscle Invasive Bladder
Guidelines)
Mr Damian Hanbury (Renal Guidelines)
Professor Tom McNicholas (Superficial Bladder
Guidelines)
Dr Philip Savage (Testicular Guidelines)
Mr Suks Minhas (Penile Guidelines)
Date Written
August 2011
Updated
February 2013 (sarcoma pathway
added)
Review Date
August 2014
Document ratified by NSSG on
16th September 2011
1
These Clinical Guidelines have been agreed by:
Name: Dr Jane Halpin
Position: Chair of Network Board
Organisation: NHS Hertfordshire
Date agreed: 19th September 2011
Name: Mr Jim Adshead
Position: Urology NSSG Chair
Organisation: East & North Herts Hospitals NHS
Trust
Date agreed: 16th September 2011
Name: Mr Suks Minhas
Position: Lead Clinician of the Supranetwork MDT
for Penile Cancer
Organisation: University College London Hospital
Date agreed: 4th August 2011
Name: Dr Phillip Savage
Position: Lead Clinician of the Supranetwork MDT
for Testicular Cancer
Organisation: Imperial College NHS Trust London
Date agreed: 2nd August 2011
Agreed by email on 2nd August
2011
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Contents
1.
2.
3.
Team Configuration in MVCN
1.1 Primary Care Referrals
1.2 Supranetwork Referrals
Renal Cell Carcinoma
2.1 Introduction
2.2 Diagnosis and classification
2.3 Staging System
2.4 Table 1: The 2009 TNM staging classification system
2.5 Histopathological classification
2.6 Other renal tumours
2.7 Radiological investigatins of RCC
2.8 Renal biopsy
2.9 Guidelines for the primary treatment of RCC
2.10 Nephron-sparing surgery
2.11 Laparoscopic radical and partial nephrectomy
2.12 Table 2: 2010 reccomendations for primary surgical treatment
of RCC according to stage
2.13 Minimally invasive alternative treatment
2.14 Adjuvant therapy
2.15 Surgical treatment of metastatic RCC (mRCC)
2.16 Radiotherapy for metastases
2.17 Systemic therapy for mRCC
2.17.1 Chemotherapy
2.17.2 Immunotherapy
2.17.3 Angiogenesis inhibitor drugs
2.17.4 Table 3: 2010 EAU evidence-based recommendations for
first and second-line systemic therapy in mRCC
2.17.5 Recommendations for systemic therapy
2.18 Surveillance following surgery for RCC
2.18.1 Table 4: Example of a proposed follow-up algorithm for
surveillance after treatment for RCC with combined patient risk
profile and treatment efficacy
Muscle Invasive and Metastatic Bladder Cancer
3.1 Introduction
3.2 Classification
3.2.1 TNM staging (TNM) 2002 (UICC, International Union against
Cancer)
3.2.2 Histological grading
3.3 Risk factors
3.4 Diagnosis
3.4.1 Symptoms
3.4.2 Cystoscopy and TUR
3.5 Staging
3.5.1T-staging
3.5.2 N-staging
3.5.3 M-staging
3.5.4 Guidelines on diagnosis and staging
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3.6 Pathology
3.6.1 Guidelines on assessment of tumour specimens
3.7 Treatment of Muscle Invasive Bladder Cancer: Cystectomy
3.7.1 Radical cystectomy
3.7.1.1 Background
3.7.1.2 Indications
3.7.1.3 Surgery
3.7.1.4 Morbidity and mortality
3.7.1.5 Survival rates
3.7.2 Recommendations
3.7.3 Urinary diversion after radical cystectomy
3.7.4 Ileal conduit
3.8 Treatment: Definiative Radiotherapy
3.8.1 External beam radiotherapy
3.8.2 Interstitial brachytherapy
3.8.3 Radiotherapy and chemotherapy
3.8.4 Radiosensitizers
3.8.5 Palliation Radiotherapy
3.8.6 Guidelines
3.9 Treatment: Systemic Chemotherapy
3.9.1 Introduction
3.9.2 Neo-adjuvant chemotherapy
3.9.3 Adjuvant chemotherapy
3.9.4 Metastatic disease
3.9.4.1 Chemotherapy protocols
3.9.4.2 Prognostic factors
3.9.5 Guidelines on chemotherapy
3.10 Follow-up: After with curative intent
3.10.1 Rational for follow-up
3.10.2 Cystecomy
3.10.3 Radiotherapy
Non Muscle Invasive (superficial) Bladder TCC
4.1 Background
4.1.1 Introduction
4.1.2 Referral process
4.1.2.1 Referral guideline for Haematuria or suspicion of bladder
cancer
4.1.2.2 Specialist teams
4.1.2.3 Referall pathway for high risk patients (and for those
developing more advanced disease)
4.1.3 Multidisciplinary team meeting discussion
4.2 Classification
4.2.1 Histological grading of superficial bladder tumours
4.2.1.1 WHO/ISUP grading
4.2.2 Inter and intra-observer variability in staging and grading
4.3 Risk factors
4.4 Diagnosis
4.4.1 Symptoms of TaT1 bladder tumours
4.4.2 Physical examination
4.4.3 Imaging
4.4.3.1 Intravenous urography
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5.
4.4.3.2 Ultrasonography
4.4.3.3 Cross Sectional imaging
4.4.4 Urinary cytology
4.4.5 Urine molecular tests
4.4.6 Cystoscopy
4.4.7 Transurethral resection of TaT1 bladder tumours
4.4.8 Bladder biopsies
4.4.9 Fluorescence cystoscopy (“blue light cystoscopy”)
4.4.10 Second resection
4.5 Adjuvant Treatment
4.5.1 One, immediate, postoperative instillation
4.5.2 Additional adjuvant intravesical instillations
4.5.3 Intravesical BCG instillation (immunotherapy)
4.5.3.1 Indications for BCG
4.5.3.2 BCG toxicity
4.5.3.3 The optimal schedule for BCG
4.5.3.4 The optimal dose of BCG
4.5.3.5 Recommendations for use of BCG
4.5.4 Predicting recurrence and progression in TaT1 tumours
4.5.4.1 Recommendations for intravesical chemotherapy or BCG
immunotherapy
4.5.5 Treatment of failures of instillation therapy
4.5.6 Recommendations for follow up cystoscopy for TaT1 bladder
cancer
Appendix 1: Referall guidelines for Haematuria or suspicion of
bladder cancer
Prostate Cancer
5.1 Background information
5.1.1 Urgent referral from GP
5.1.2 Indications for referall
5.1.3 Diagnosis of suspected prostate cancer
5.1.4 Discussion at MDT
5.2 Risk factors
5.3 Diagnosis
5.3.1 DRE
5.3.2 PSA
5.3.3 TRUS
5.3.4 TRUS biopsies of the Prostate
5.4 Staging
5.5 Classification TNM Staging (UICC 5th edition 1997)
5.6 Treatment options
5.6.1 Localised Prostate Cancer
5.6.1.1 Deferred Treatment or Active Surveillance
5.6.1.2 Radical Prostatectomy
5.6.1.3 Radiotherapy
5.6.1.4 High Intensity Focused Ultrasound (HIFU) and Cryotherapy
5.6.2 PSA only recurrence after definitive treatment
5.6.2.1 Radiation therapy for PSA-only recurrence
5.6.2.2 Hormonal therapy for PSA-only recurrence
5.6.2.3 Guidelines for follow-up after treatment with curative intent
5.6.3 Locally Advanced Prostate Cancer
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7.
5.6.4 Metastatic Prostate Cancer
5.6.4.1 Maximal androgen blockade (MAB)
5.6.4.2 Intermittent androgen blockade
5.6.4.3 Guidelines for follow-up after hormonal treatment
5.6.4.4 Managing the Complications of Hormonal Therapy
5.6.4.5 Hormone-Refractory Prostate Cancer
5.6.4.6 Chemotherapy
5.6.4.7 Oestrogens and Steroids
5.6.4.8 Imaging
5.6.4.9 Bone targeted therapies
5.6.4.10 Pelvic Trageted Therapies
5.5.6 Hormone Refactory Prostate Cancer
5.6.6 Palliative Care for Prostate Cancer Patients
5.6.6.1 Bone Metastases
5.6.7 Radiotherapy to prevent Gynaecomastia
5.6.7.1 Palliative External beam Radioterapy technique
Pathology
6.1 Introduction
6.2 Siting of the service
6.3 Governance
6.4 Specimen Types
6.5 Specimen Examination
6.6 Immunohistochemistry
6.7 Radical Prostatectomies
6.8 Microscopy
6.9 TNM Pathological staging (6th edition, UICC)
6.10 Urinary bladder, urethral and ureteric biopsies, cystectomies
6.11 Reporting of small biopsy specimens
6.12 Reporting of frozen sections
6.13 TNM Pathological staging (6th edition, UICC)
6.13.1Renal pelvis and ureter
6.13.2 Urinary bladder
6.14 Orchidectomies
6.15 Gross Examination
6.16 Nephrectomies
Rarer Cancer and Supportive Care Referral Guidelines
7.1 Clinical and referral guidelines
7.2 Supranetwork guidelines
7.3 Generic guidance
APPENDICES
Appendix 1
UCLH Guidelines for Referral, Investigation and Management of
Cancer of the Penis
Appendix 2
Charing Cross Guidelines for Referral, Investigation and
Management of Testicular Cancer
Appendix 3
MVCN Two Week Wait Referral Proforma
Appendix 4
Abbreviations used in this document
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83
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85
104
176
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Appendix 5
Sarcoma Pathway
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Team Configuration in MVCN
The network catchment population includes 1.3 million people living in Hertfordshire and
South Bedfordshire. In accordance with the Urology IOG all high risk specialist surgery
was centralised on 16th October 2009 to the South Bedfordshire and Hertfordshire
Urology Specialist Surgical Cancer Centre at Lister Hospital, Stevenage. All oncology
treatments are offered at the Mount Vernon Cancer Centre.
Local Trust
Hospitals
Level of
Designation
and Lead
Clinician
Referring
PCTs
Single
Referral
Contact Point
Fax Number
Catchment *
West
Hertfordshire
Hospital
NHS Trust
Watford General
Hospital
Local MDT
NHS
Hertfordshire
(West Herts
Population)
01727 897492
549,600
NHS
Hertfordshire
(E&N
Population)
01438 781835
545,800
Luton
Teaching
PCT and
Bedfordshire
PCT
01582 497910
or
01582 497911
Hemel
Hempstead
Hospital
East & North
Hertfordshire
NHS Trust
Mr Manoah
Pancharatnam
Diagnostic
Service
St Albans City
Hospital
Diagnostic
Service
Lister Hospital,
Stevenage
Specialist MDT
/ diagnostic
service
Queen Elizabeth
II Hospital, WGC
Mr J Adshead
Diagnostic
service
312,400
Luton and
Dunstable
NHS
Foundation
Trust
Luton and
Dunstable
Hospital
Foundation Trust
Local MDT /
diagnostic
service
Mr A Alam
* as per ONS 2009 mid year population estimates
All three trusts host diagnostic services at all sites within the trusts. Watford and Luton &
Dunstable hospitals host a local MDT meeting, and Lister hospital hosts the Specialist
MDT, which also acts as a local MDT for it’s catchment population.
1.1 Primary Care Referrals
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GP’s will refer all patients with suspected urological cancer under the two week wait
(2WW) referral scheme. All referrals for each PCT locality are referred to a single
contact point, which feeds into the Local MDT. The referral proforma (see appendix 3)
should be faxed to the appropriate fax number at the bottom of the proforma, or in the
above table.
1.2 Supranetwork Referrals
Network Clinical Guidelines are followed for referral of patients with penile and testicular
cancer to Supranetwork MDTs, please see individual sections for more detail:


Penile Cancers are referred to the Supranetwork MDT at UCLH (catchment
population 7 million).
Testicular Cancers are referred to the West London Testicular Cancer
Supranetwork MDT at Imperial (catchment population 3 million). They will be
discussed here but are generally managed at Mount Vernon Cancer Centre with
the exception of those patients who require complex surgery which will be
undertaken at Imperial.
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1. Renal Cell Carcinoma
(Text update April 2010)
B. Ljungberg (Chairman), N. Cowan, D.C. Hanbury, M. Hora,
M.A. Kuczyk, A.S. Merseburger, P.F.A. Mulders, J-J. Patard,
I.C. Sinescu
Adapted for use within MVCN by DC Hanbury and P Nathan
Eur Urol 2001 Sep;40(3):252-5
Eur Urol 2007 Jun;51(6):1502-10
1.1 Introduction
Renal cell carcinoma (RCC) represents 2-3% of all cancers, with the highest incidence
occurring in Western countries. In Europe, until recently, there was a general annual
increase of 2% in the incidence. However, incidence rates of RCC have now stabilised
or declined in some countries (Sweden, Denmark), while other European countries are
still showing an upward trend in the incidence of RCC.
The use of imaging techniques such as ultrasound (US) and computerised tomography
(CT) has increased the detection of asymptomatic RCC. In addition, during the last 10
years, mortality rates have generally stabilised and declined prominently in some
European countries. The peak incidence of RCC occurs between 60 and 70 years of
age, with a 1.5:1 ratio of men to women. Aetiological factors include lifestyle factors,
such as smoking, obesity and hypertension. The most effective prophylaxis is to avoid
cigarette smoking and obesity.
1.2 Diagnosis and classification
More than 50% of RCCs are diagnosed incidentally. Asymptomatic RCCs are generally
smaller and of a lower stage than symptomatic RCCs. In their natural clinical course,
RCCs remain asymptomatic and non-palpable until late. The classic triad of flank pain,
gross haematuria and palpable abdominal mass is seldom found (6-10%). Clinical
symptoms include macroscopic haematuria, palpable mass, arising varicocele or
bilateral lower extremity oedema; these symptoms should initiate radiological
examinations.
Paraneoplastic symptoms (e.g. hypertension, weight loss, pyrexia, neuromyopathy,
anaemia, polycythaemia, amyloidosis, elevated erythrocyte sedimentation rate and
abnormal liver function) are found in approximately 20-30% of patients with RCC. About
20-30% of patients with symptoms present as a result of metastatic disease.
Total renal function should always be evaluated. In patients with any sign of impaired
renal function, a renal scan and total renal function evaluation should be undertaken to
optimise the treatment decision.
1.3 Staging system
The current UICC 2009 TNM (Tumour Node Metastasis) classification is recommended
for the staging of RCC.
2.4 Table 1: The 2009 TNM staging classification system
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T
TX
T0
T1
T1a
T1b
T2
T2a
T3
T3a
T3b
T3c
T4
Primary tumour
Primary tumour cannot be assessed
No evidence of primary tumour
Tumour ≤ 7 cm in greatest dimension, limited to
the kidney
Tumour ≤ 4 cm in greatest dimension, limited
to the kidney
Tumour > 4 cm but ≤ 7 cm in greatest
dimension
Tumour > 7 cm in greatest dimension, limited to
the kidney
Tumour > 7 cm in greatest dimension but
T2b
Tumours > 10 cm limited to the kidney
Tumour extends into major veins or perinephric
tissues, but not into the ipsilateral adrenal gland
and not beyond Gerota’s fascia
Tumour grossly extends into the renal
vein or its segmental (muscle-containing)
branches, or tumour invades perirenal
and/or renal sinus (peripelvic) fat but not
beyond Gerota’s fascia
Tumour grossly extends into the vena cava
below diaphragm
Tumour grossly extends into vena cava or
its wall above the diaphragm or invades the
wall of the vena cava
Tumour invades beyond Gerota’s fascia (including
contiguous extension into the ipsilateral adrenal
gland)
N
Regional lymph nodes
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis in a single regional lymph node
N2
Metastasis in more than one regional lymph node
M
Distant metastasis
M0
No distant metastasis
M1
Distant metastasis
A help desk for specific questions about TNM classification is available at
http://www.uicc.org/tnm.
2.5 Histopathological classification
Fuhrman nuclear grade is the most commonly used grading system. The most
aggressive pattern observed defines the Fuhrman grade. RCC comprises four main
different subtypes with genetic and histological differences: clear cell RCC (cRCC, 8090%), papillary RCC (pRCC, 10-15%), chromophobe RCC (ch RCC4-5%), and
collecting duct carcinoma (1%). Rarer subtypes have also been described. Generally,
the RCC types have different clinical courses and responses to therapy.
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Fuhrman grading and RCC subtype classification are recommended. There are several
integrated prognostic systems and nomograms that combine dependent prognostic
factors, which can be useful for predicting survival and differentiating follow-up.
Molecular markers and gene expression profiles appear promising for the prediction of
survival, but cannot be recommended yet in routine practice.
2.6 Other renal tumours
The common RCC types account for 85-90% of all renal malignancies. The remaining
10-15% of renal tumours include a variety of uncommon carcinomas, a group of
unclassified carcinomas, and several benign kidney tumour masses.
•
•
•
•
•
Except for angiomyolipomas, most of these less common renal tumours cannot
be differentiated from RCC by radiological imaging and should therefore be
treated in the same way as RCC.
Renal cysts with a Bosniak classification
In oncocytomas verified on biopsy, follow-up can be considered as an option.
In angiomyolipomas, treatment (surgery, thermal ablation, and selective arterial
embolisation) can be considered when the tumour > 4 cm. When possible, a
nephron-sparing procedure should be performed.
A standardised oncological programme does not exist for advanced uncommon
types of renal tumours.
2.7 Radiological investigations of RCC
Radiological investigations of RCC should include CT imaging, before and after
intravenous contrast to verify the diagnosis and provide information on the function and
morphology of the contralateral kidney and assess tumour extension, including
extrarenal spread, venous involvement, and enlargement of lymph nodes and adrenals.
Abdominal US and magnetic resonance (MR) imaging are alternatives to CT. Contrastenhanced US can be helpful in specific cases.
Magnetic resonance imaging can be reserved for patients with possible venous
involvement, or allergy to intravenous contrast. Chest CT is the most accurate chest
staging; a routine chest X-ray should be done as a minimum. Renal masses may be
classified as solid or cystic by imaging criteria. For evaluating solid renal masses, the
presence of enhancement is the most important criteria for differentiating malignant
lesions.
For evaluating renal cystic masses, the Bosniak classification may be used.
Other diagnostic procedures (bone assessment – MRI preferred to bone scan, brain –
MRI or CT) should only be considered if indicated by clinical symptoms or laboratory
results in selected cases. Renal arteriography and inferior venacavography have only a
limited role in the work-up of selected patients with kidney tumours. The true value of
positron emission tomography (PET) in the diagnosis and follow-up of RCC remains to
be determined and is currently not standard. In patients with any sign of impaired renal
function, an isotope renogram and total renal function evaluation should be considered
to evaluate the need to preserve renal function.
2.8 Renal biopsy
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There is an increasing indication for biopsy of renal tumours, as in ablative therapies and
in patients being treated with surveillance or systemic therapy without previous
histopathology. Core biopsy has demonstrated a high specificity and sensitivity for
determining eventual malignancy, but about 20% of biopsies are non-conclusive.
Percutaneous biopsy is rarely required for large renal masses scheduled for
nephrectomy since it will not alter management. Fine-needle biopsy has only a limited
role in the clinical work-up of patients with renal masses.
2.9 Guidelines for the primary treatment of RCC
Until recently, the standard for curative therapy of RCC was radical nephrectomy with
complete removal of the tumour-bearing kidney with perirenal fat and Gerota’s fascia.
For localised RCCs, nephron-sparing surgery is recommended. Radical nephrectomy is
recommended for patients with localised RCC, who are not suitable for nephron-sparing
surgery due to locally advanced tumour growth, when partial resection is technically not
feasible due to an unfavourable localisation of the tumour, or when the patient’s general
health has significantly deteriorated. Complete resection of the primary RCC either by
open or laparoscopic surgery offers a reasonable chance for cure.
If pre-operative imaging is normal, routine adrenalectomy is not indicated.
Lymphadenectomy should be restricted to staging because extended lymphadenectomy
does not improve survival. In patients who have RCCs with tumour thrombus and no
metastatic spread, prognosis is improved after nephrectomy and complete
thrombectomy.
Embolisation of the primary tumour is indicated in patients with gross haematuria or local
symptoms (e.g. pain), in patients unfit for surgical intervention, and before surgical
resection of large skeletal metastases. No benefit is associated with tumour embolisation
before routine radical nephrectomy.
2.10 Nephron-sparing surgery
Absolute indications for partial nephrectomy are anatomical or functional solitary kidney
or bilateral RCC. Relative indications are a functioning opposite kidney affected by a
condition that might impair renal function and hereditary forms of RCC with a high risk of
developing a tumour in the contralateral kidney.
Localised unilateral RCC with a healthy contralateral kidney is an indication for elective
surgery.
Nephron-sparing surgery is recommended for patients with localised RCC, as
recurrence-free and long-term survival rates are similar to those for radical nephrectomy.
Even in selected patients with a tumour diameter of up to 7 cm, nephron-sparing surgery
has achieved results equivalent to those of a radical approach. If the tumour is
completely resected, the thickness of the surgical margin (> 1 mm) does not correlate
with the likelihood of local recurrence. If RCCs of larger size are treated with nephronsparing surgery, follow-up should be intensified, as there is an increased risk of
intrarenal recurrences.
2.11 Laparoscopic radical and partial nephrectomy
Laparoscopic radical nephrectomy has a lower morbidity compared with open surgery. It
has become an established surgical procedure for RCC. Whether done retro- or trans-
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peritoneally, the laparoscopic approach must duplicate established, open surgical,
oncological principles. Long-term outcome data indicate equivalent cancer-free survival
rates versus open radical nephrectomy. Thus, laparoscopic radical nephrectomy is now
considered the standard of care for patients with T1 and T2 RCCs, who are not treatable
by nephron-sparing surgery. Laparoscopic radical nephrectomy should not be performed
in patients with T1 tumours for whom partial resection is indicated. Laparoscopic
nephrectomy is expected to become a widely available treatment option and should be
promoted in centres treating RCC.
In experienced hands, partial laparoscopic nephrectomy may be an alternative to open
nephron-sparing surgery in selected patients. The optimal indication for laparoscopic
nephron-sparing surgery is a relatively small and peripheral tumour. Laparoscopic partial
resection has a longer intra-operative ischaemia time than open partial nephrectomy and
therefore carries a higher risk for reduced long-term renal function. It also has a higher
surgical complication than open surgery.
However, the oncological outcome seems comparable in available series. Roboticassisted partial nephrectomy has been introduced, but requires further evaluation and
more mature data before any conclusive recommendations can be made.
MVCN: Open and laparoscopic radical nephrectomy is available at all Surgical Cancer
Units in the network ie Lister, Watford and Luton. Locally advanced tumours requiring
PLND and/or IVC exploration for emboli below the diaphragm should be performed at
Lister jointly with vascular surgical colleagues. Patients with tumour emboli extending
into the right atrium should be referred directly to colleagues at the Royal Marsden.
2.12 Table 2: 2010 recommendations for primary surgical treatment of RCC
according to stage
Stage
Surgery
T1
Nephron-sparing
surgery
Radical
nephrectomy
Recommendations
Open
Laparoscopic
Laparoscopic
Open
T2
T3,T4
Radical
nephrectomy
Laparoscopic
Open
Nephron-sparing
surgery
Radical
nephrectomy
Open
Laparoscopic
Recommended standard
Optional in experienced centres
In patients not suitable for
nephron-sparing surgery
Optional in patients not suitable
for nephron-sparing surgery
Recommended standard
Adequate and recommended,
but carries a higher morbidity
Feasible in selected patients in
experienced centres
Recommended standard
Feasible in selected patients
Conclusion: Radical nephrectomy, preferably laparoscopic, is recommended for patients
with localised RCC, who are not suitable for nephron-sparing surgery. Open partial
nephron-sparing surgery remains the standard of care. Laparoscopic partial
nephrectomy should be limited to experienced centres.
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MVCN: Tumours suitable for nephron-sparing surgery should be discussed at SMDT
and referred to Lister for surgery or ablative therapy. Patients suitable for nephronsparing surgery can be offered open or laparoscopic or robotic-assisted laparoscopic
partial nephrectomy
2.13 Minimally invasive alternative treatment
Minimally invasive techniques, such as ablation with percutaneous radio-frequency,
cryotherapy, microwave, and high-intensity focused US (HIFU), are suggested
alternatives to surgery. Potential advantages of these techniques include reduced
morbidity, outpatient therapy, and the ability to treat high-risk patients not fit for
conventional surgery.
These experimental treatments might be recommended for selected patients with small,
incidentally found, renal cortical lesions, elderly patients, patients with a genetic
predisposition to multiple tumours, patients with a solitary kidney, or patients with
bilateral tumours. The oncological efficacy remains to be determined for both
cryotherapy and RFA, which are the most often used minimally invasive techniques.
Current data suggest that cryoablation, when performed laparoscopically, results in
fewer re-treatments and improved local tumour control compared with RFA. For both
treatments, tumour recurrence rates are higher compared with nephron-sparing surgery.
Further research is needed to determine the oncological success rate and complications
associated with these procedures.
MVCN: Some (usually more elderly or high risk) patients suitable for nephron-sparing
surgery will be offered laparoscopic cryoablation which is available at Lister. Occasional
high-risk cases will be referred for CT-guided radiofrequency ablation to colleagues at
UCH since this technique is not yet available at Lister. All patients who may require
perioperative renal support should be referred to Lister for surgery where there is inpatient dialysis available.
2.14 Adjuvant therapy
Although there is no current data supporting adjuvant therapy with targeting agents,
three worldwide phase III randomised trials are ongoing. Outside controlled clinical trials,
there is no indication for adjuvant therapy following surgery. The current UK NCRN
badged adjuvant study is SORCE. Patients with a Leibovich risk score post nephrectomy
of intermediate or poor prognosis should be referred to Dr Nathan for consideration of
the study.
2.15 Surgical treatment of metastatic RCC (mRCC)
Nephrectomy of the primary tumour is curative in intent only if surgery can excise all
tumour deposits. For most patients with mRCC, nephrectomy is only palliative. In a
meta-analysis of two randomised studies, comparing nephrectomy + immunotherapy
versus immunotherapy alone, increased long-term survival was found in patients who
underwent prior nephrectomy.
In patients with a good performance status (PS) who go on to receive immunotherapy
with IFN-α, tumour nephrectomy can be recommended. However most patients now do
not receive interferon but receive newer targeted agents instead. With targeted agents,
there is no current knowledge whether cytoreductive surgery is advocated before or after
successful medical therapy. However, in the absence of available evidence,
14
cytoreductive nephrectomy is recommended for selected patients depending upon
disease burden within and outside the kidney.
Complete removal of metastases may contribute to improved clinical prognosis.
Metastasectomy should be considered in selected patients with resectable disease,
good PS, a disease free interval of > 1 year,good prognosis according to the MSKCC
scoring system and after a trial of observation to look for the development of other
metastatic deposits. It should also be considered in patients with residual and
resectable metastatic lesions, who have previously responded to systemic therapy.
MVCN: Patients with metastatic disease at presentation should be discussed at SMDT
or directly with Dr Nathan prior to surgery being scheduled. This group of patients may
be suitable for one of the upcoming NCRI and EORTC studies looking at up-front
treatment with a targeted agent.
2.16 Radiotherapy for metastases
For selected patients with non-resectable brain or osseous lesions, radiotherapy can
induce significant symptom relief.
MVCN: patients with painful metastatic disease should be referred directly to a clinical
oncology colleague at Mount Vernon for consideration of palliative DXT
2.17 Systemic therapy for mRCC
2.17.1 Chemotherapy
Chemotherapy is considered ineffective in patients with RCC.
2.17.2 Immunotherapy
Available data show that immunotherapy with IFNof patients; those with good PS, a PFS of > 1 year following initial diagnosis, and
preferably the lung as the sole metastatic site. Randomised studies comparing targeting
agents in a first-line setting to IFNve demonstrated superiority for
either sunitinib, bevacizumab + IFNremains an option in selected patients as first-line therapy for mRCC. High-dose bolus
interleukin-2 (IL-2) gives durable complete responses in a limited number of patients;
however, the toxicity associated with IL-2 is substantially higher than that with IFNTo date, no superiority has been shown for treatment with either IFN-2 in mRCC
patients. Only patients with cRCC benefit clinically from immunotherapy.
A combination of cytokines, with, or without, additional chemotherapy does not improve
overall survival compared with monotherapy.
The MSKCC (Motzer) prognostic criteria can be used for risk stratification including;
Karnowsky performance status (< 80), time to diagnosis to treatment with IFNmonths), Haemoglobin (< normal), Lactate dehydrogenase (> 1.5 upper normal limit)
and corrected serum calcium (> normal). Low risk, 0 risk factor; intermediate, 1-2 risk
ctors.
2.17.3 Angiogenesis inhibitor drugs
Recent advances in molecular biology have led to the development of several novel
agents for the treatment of mRCC. In sporadic and VHL (von Hippel Lindau) cRCC, the
15
accumulation of hypoxia inducible factor (HIF) due to a defective VHL protein results in
over-expression of vascular endothelial growth factor (VEGF) and platelet-derived
growth factor (PDGF), promoting neo-angiogenesis. This process substantially
contributes to the development and progression of RCC.
At present, four targeting drugs have been approved both in the USA and in Europe for
mRCC, while other agents have shown significant efficacy in randomised controlled
trials.
Tyrosine kinase inhibitors (TKIs): several TKIs have shown efficacy in cRCC with
increased PFS as both first- and second-line treatments of mRCC.
•
•
•
•
Sorafenib is an oral multikinase inhibitor with proven increased PFS as a secondline treatment after failure of systemic immunotherapy.
Sunitinib is an oral TKI. In a phase III first-line study comparing sunitinib with IFNα, sunitinib achieved a longer PFS time (11 months vs 5 months) in low- and
intermediate-risk patients. In patients who did not receive any post-study
treatment, overall survival was longer in the sunitinib-only treated group than in
the IFNPazopanib is an oral TKI targeting VEGF and PDGF receptors and c-Kit. In a
prospective randomised trial of pazopanib versus placebo in treatment-naive
mRCC patients and cytokine-treated patients, there was a significant
improvement in PFS from 4.2 to 9.2 months and tumour response was observed.
VEGF antibodies
Bevacizumab is a humanised monoclonal antibody that binds VEGF. A doubleblind phase III trial showed a
median 31% overall response with bevacizumab + IFN-
- and
intermediate-risk patients.
Mammalian target of rapamycin (mTOR) inhibitors, which affect the mTOR pathway,
show significant efficacy in mRCC, in other RCC types besides cRCC, and also in highrisk patients.
•
Temsirolimus is a specific inhibitor of mammalian target of rapamycin. A phase III
trial demonstrated increased overall survival in poor-risk patients with mRCC
given temsirolimus monotherapy compared with IFN- α.
•
Everolimus is an oral mTOR inhibitor. A recent phase III study in patients who
had failed previous anti-VEGF-R treatment showed a PFS of 4 months with
everolimus versus 1.9 months with placebo.
Clinical research continues into the use of these and several other new novel agents for
the primary or secondary treatment of mRCC, including monotherapy, in combination
with each other or with cytokines, or in the adjuvant setting. Only limited overall survival
data are available for these new agents and their role is still under development. In the
sunitinib randomised trial, patients crossed over from IFNmedian survival times were 20.0 versus 26.4 months for sunitinib, respectively (p =
0.03). In patients who did not receive any post-study sunitinib, the median overall
survival was 14.1 months versus 28.1 months in the sunitinib group.
16
To date, there has been no data on the curative effect of the new agents. These agents
appear to promise to stabilise mRCC for a prolonged period of time. However, their
clinical use has to be balanced against their toxicity profile and the patient’s quality of
life.
MVCN: The treatment based recommendations below for patients not entering clinical
trials are agreed upon by the UK consensus group. Currently however only one drug
(sunitinib) is approved by NICE and therefore access to the other agents in routine
practice is dependent upon a successful exceptional treatment application to the
relevant PCT.
2.17.4 Table 3:
Treatment
• First- line
• Second- line
2010 EAU evidence-based recommendations for first- and
second-line systemic therapy in mRCC
Risk or prior
treatment
Low- or intermediaterisk
mRCC
High-risk mRCC
Prior cytokine
therapy
Prior VEGFR
therapy
Prior mTOR
inhibitor therapy
Recommended
agent
Sunitinib
Bevacizumab + IFNPazopanib
Temsirolimus
Sorafenib
Pazopanib
Everolimus
2.17.5 Recommendations for systemic therapy
Tyrosine kinase inhibitors should be considered as first- or second-line treatment for
mRCC patients as shown in Table 3. Interferonoption in selected patients as first-line therapy for mRCC.
2.18 Surveillance following surgery for RCC
Surveillance following surgery for RCC allows the urologist to monitor post-operative
complications, renal function, local recurrence after partial nephrectomy or ablative
treatment, recurrence in the contralateral kidney, and development of metastases.
The method and timing of investigation has been the subject of many publications. Using
different scoring systems and algorithms, patients can be categorised as at low-,
intermediate- or high-risk of developing metastases. Despite extensive research, there is
no general recommendation for the method and timing of investigations for surveillance.
In fact, there is no evidence for whether early versus later diagnosis of recurrence
improves survival. However, follow up remains important to increase knowledge of the
disease and should be performed by the urologist, who should record the time elapsed
to recurrence or metastatic development. Follow-up also allows metastases to be
identified early.
Early identification of metastases increases the possibility of surgical resection and
efficacy of systemic treatment at a time when the tumour burden is as low as possible.
This is particularly important with ablative therapies, such as cryotherapy and RFA,
where the local recurrence rate is higher than conventional surgery and the patient may
17
still be cured by repeat ablative therapy or radical nephrectomy. In metastatic disease,
more extended tumour growth can reduce the possibility of surgical resection, which is
considered the standard therapy in cases of resectable and preferably solitary lesions. In
addition, within clinical trials, an early diagnosis of tumour recurrence might enhance the
efficacy of a systemic treatment if the tumour burden is low.
The urologist can therefore be selective in the use of imaging and the need for intensive
surveillance. Although there is no evidence-based standard for the follow-up of patients
with RCC, there are several scoring systems and nomograms for predicting tumour
recurrence and metastases. Using these nomograms, several stage-based surveillance
regimes have been proposed. However, none include ablative therapies. There is
therefore a need for a surveillance algorithm that monitors patients after treatment for
RCC that recognises not only the patient’s risk profile but also treatment efficacy. An
example is given in Table 4; please note this is not an EAU recommendation.
For patients with metastatic disease, an individual follow-up plan is required.
MVCN: Surveillance can follow local practice that is by urologists, medical oncologists
or general practitioner as deemed appropriate
2.18.1 Table 4: Example of a proposed follow-up algorithm for surveillance after
treatment for RCC with combined patient risk profile and treatment efficacy
(This is an example of a follow-up scheme; grade of recommendation C)
Treatment
Risk profile
and schedule
Low
Intermediate
High
Treatment
RN/PN only
RN/PN/cryo/
RN/PN/cryo/
RFA
RFA
6 months
CXR and US
CT
CT
1 year
CXR and US
CXR and US
CT
2 years
CXR and US
CT
CT
3 years
CXR and US
CXR and US
CT
4 years
CXR and US
CXR and US
CT
5 years
CXR and US
CT
CT
> 5 yrs
Discharge
CXR Yearly and CXR/CT in
US
alternate years
CT = CT of chest and abdomen; cryo = cryotherapy;
CXR = chest X-ray; PN = partial nephrectomy; RFA = radiofrequency
ablation. RN = radical nephrectomy; US = ultrasound of kidneys and renal bed.
This short booklet text is based on the more comprehensive EAU guidelines
(ISBN 978-90-79754-70-0), available to all members of the European
Association of Urology at their website - http://www.uroweb.org.
18
2. Muscle Invasive and Metastatic Bladder Cancer
3.1 Introduction


th
Transitional cell cancer of the bladder is the 5 most common malignancy in males.
Between 7000– 8000 new cases are recorded annually in the UK, representing 25%
of all new urological cancers. Mean age at presentation is 72 years with a
male:female ratio of 3:1. Approximately 25-30% of patients with transitional cell
carcinoma (TCC) of the urinary bladder will be diagnosed as having muscle-invasive
or metastatic tumour. In addition, approximately 30% of patients who are initially
diagnosed with a superficial TCC will develop an invasive tumour during follow-up
after organ-preserving therapy.
Evidence from the BAUS database suggests that only approximately 37% of newly
diagnosed bladder cancers present via the 2 week referral system, 30% of patients
present via standard referral system,15% via a routine referral and 5% as an
emergency. The median times from referral to consultation, diagnosis and definitive
treatment are 14, 31 and 65 days respectively. The 2 week referral system has not
made a significant impact on these waiting times.
3.2 Classification
3.2.1 TNM staging (TNM) 2002 (UICC, International Union Against Cancer)
Table 1: 2002 TNM classification of urinary bladder cancer
T (Primary tumour)






TX Primary tumour cannot be assessed
T0 No evidence of primary tumour Ta Non-invasive papillary carcinoma
Tis Carcinoma in situ (‘flat tumour’) T1 Tumour invades subepithelial connective tissue
T2 Tumour invades muscle
T2a Tumour invades superficial muscle (inner half)
T2b Tumour invades deep muscle (outer half)
T3 Tumour invades perivesical tissue: T3a Microscopically T3b Macroscopically
(extravesical mass)
T4 Tumour invades any of the following: prostate, uterus, vagina, pelvic wall,
abdominal wall T4a Tumour invades prostate, uterus or vagina T4b Tumour invades
pelvic wall or abdominal wall
N (Lymph nodes)




NX
N0
N1
N2

N3
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single lymph node 2 cm or less in greatest dimension
Metastasis in a single lymph node more than 2 cm but not more than
5cm in greatest dimension, or multiple lymph nodes, none more than
5cm in the greatest dimension.
Metastasis in a lymph node more than 5 cm in greatest dimension
M (Distant metastasis)



MX Distant metastasis cannot be
assessed
M0 No distant metastasis
M1 Distant metastasis
19
3.2.2 Histological grading
Table 2: Histological grading of WHO and International Pathology Consensus
Committee 1988
PTNM pathological The pT, pN, and pM categories correspond to the T, N, and M categories
classification
of the TNM classification
G
GX
G1
G2
G3
Histopathological grading
Grade of differentiation cannot be assessed
Well differentiated
Moderately differentiated
Poorly differentiated/undifferentiated


More than 90% of bladder cancers are found to be TCC.
The remainder are squamous cell carcinoma (SCC) , adenocarcinoma, small cell
carcinomas or sarcomas. Bladder tumours are considered superficial (Tis, Ta, T1) or
infiltrative (T2, T3, T4) based on cystoscopy, TUR, imaging studies and histopathological
findings.
3.3 Risk Factors
 The risk factors for the development of bladder cancer are described in detail in the
guidelines on superficial bladder cancer. Chronic infection, long term intermittent self
catheterisation, residual urine and foreign bodies (for example indwelling catheters) are
associated with invasive bladder cancer. However, these tumours are mainly squamous
cell or adenocarcinomas. Similarly, tumours in bilharziasis are mostly squamous cell
and only about one third are transitional cell carcinomas. Tumours that arise in
persisting urachal remnants are usually Adenocarcinomas tumours.
3.4 Diagnosis
3.4.1 Symptoms
 Painless haematuria is a common finding.
 Urgency, dysuria, increased frequency and pelvic pain.
 Renal failure secondary to ureteric obstruction.
3.4.2 Cystoscopy and TUR
The diagnosis of bladder cancer depends on



Cystoscopy, TUR and pathological evaluation of the resected lesion. Cystoscopy can
provide good information on the extent of the tumour.
The TUR specimen has to include the muscularis propria, which is achieved by separate
TUR of the tumour base (fractional resection).
EUA
3.5 Staging
3.5.1 T-staging
20


TUR and bimanual palpation
Imaging

Intravenous pyelography / CT Urogram

Ultrasonography

Computed tomography (CT)
Abdomen
Chest
Computed tomography (CT) cannot differentiate accurately between organ-confined and
extravesical extension. The correlation between CT findings and tumour extent in cystectomy
specimens is 65-80%. The imaging modality is helpful for monitoring patients undergoing neoadjuvant chemotherapy or bladder-sparing treatment modalities.

Magnetic resonance imaging (MRI)
MRI is the staging investigation of choice in muscle invasive bladder cancer. Similarly to CT,
magnetic resonance imaging (MRI) cannot detect microscopic extension into the perivesical
fat. The staging error remains about 30%.
If a local tumour is suspected to be invasive, patients should undergo imaging studies to
assess the extent of invasion prior to undergoing TUR if possible.
3.5.2 N-staging
 CT and MRI will miss microscopic nodal disease in up to 70% of cases .
 Lymphadenectomy is the only method capable of excluding metastatic disease to the
lymph nodes. The recommended extent of lymphadenectomy has not been assessed in
prospective investigations.
3.5.3 M-staging
 Chest x-ray mandatory.
 Bone scan should be done if bone pain, hypercalcaemia or abnormal alkaline
phosphatases.
 Ultrasonography can be used to demonstrate liver metastases.
3.5.4 Guidelines on Diagnosis and Staging
Mandatory evaluations
 Physical examination
 Cystoscopy & EUA
 TURBT
 Biopsy of the tumour base
 Biopsy of the prostatic urethra/bladder neck
 Chest X-ray
 IVP or abdominal sonography / CT Urogram
 Abdominal CT/MRI
Optional evaluations
21

Bone scan
3.6 Pathology
3.6.1 Guidelines on Assessment of Tumour Specimens
Mandatory evaluations
Depth of invasion (categories pT2 vs pT3a, pT3b or pT4)
Margins with special attention paid to the radial margin
Histological subtype, if it has clinical implications
Extensive lymph node representation (more than 16)
Optional evaluations
Bladder wall blood vessel invasion
Pattern of muscle invasion
3.7 Treatment of Muscle Invasive Bladder Cancer: Cystectomy
3.7.1 Radical cystectomy
3.7.1.1 Background
 Radical cystectomy is the gold standard treatment in most countries for muscleinvasive bladder tumours. Bladder-sparing surgery in carefully selected cases
together with neoadjuvant or adjuvant chemotherapy and/or radiation may be a
reasonable alternative to radical cystectomy. Renewed interest in quality-of-life issues
has increased interest in bladder preservation treatments

Performance status and age can influence the choice of therapy, with cystectomy
being reserved for younger patients without concomitant disease.

Neoadjuvant chemotherapy should be offered to patients with bulky pT2, pT3 or N+ve
disease. Repeat cross-sectional imaging is performed following 2 – 4 weeks following
the 3rd cycle of chemo-therapy to assess response. Further definitive treatment with
cystectomy or radical radiation is planned accordingly
3.7.1.2 Indications
The primary indications for cystectomy is





Muscle invasive bladder cancer T2 – T4a, N0-NX,M0
high-risk superficial tumours (T1 G3 and BCG-resistant Tis
extensive papillary disease that cannot be controlled with conservative measures
intractable LUTS/bleeding/contracted bladder (symptom control)
Salvage cystectomy is indicated for non-responders to non surgical therapies or
relapse after bladder-sparing treatments
Contra-indications for cystectomy

are major co-morbidity and patients not willing to accept the surgical risks.
22

Patients should be informed of the staging error between clinical and pathological
stages which may be was as high as 44%, and has been found to be the highest for
tumours in the T2 category. The frequency of regional lymph node metastases
depends on the T-stage, ranging from less than 10% in T1 to almost 33% in the T3-T4
category
3.7.1.3 Surgery
 Radical cystectomy should be performed in high volume cancer centres performing a
minimum of 50 pelvic operations per year. (Radical prostatectomy and cystectomy
combined).
 Sufficient HDU/ITU support should be available.
 Patients with impaired renal function should undergo surgery in centres with renal
support.
MVCN: Surgery is perfomed by four surgeons at the Lister centre, often in teams of two
offering, where suitable, radical cycsectomy either with ileal diversion or continent diversion.
The surgeons performing surgery at the centre are Mr Greg Boustead, Mr Jim Adshead, Mr
Tim Lane, Mr Manoah Pancharatnam.
Where it is suitable the ablative part of the surgery is more frequently performed robotically.
3.7.1.4 Morbidity and mortality
 Patients should be aware of
o
The operative mortality risk is 1.2% - 3.7% in high volume centres.
o
Morbidity is around 20-30%
3.7.1.5 Survival rates
 The 5-year survival rate is usually reported to be in the range of 40-60%.

The use of neo-adjuvant chemotherapy confers a small survival advantage (5-8%).
Care must be taken to ensure that there is no more than 12 weeks delay to
Cystectomy. In a recent report,

The 5-year survival rates with no pre-operative therapy were
o
75% for stage pT1,
o
63% for stage pT2,
o
31% for stage pT3 and
o
21% for stage pT4 disease.
o
Approximately 10% of cystectomy specimens are without tumour (stage pT0)
due to radical TUR or neo-adjuvant chemotherapy. Whether or not this confers
a survival advantage is controversial. Tumour stage and nodal involvement
are the only independent predictors of survival (less than 3 nodes positive out
of 16 or more has a better prognosis).
23
3.7.2 Recommendations
1. Radical cystectomy in T2-T4a, N0-NX, M0 and recurring T1 G3 and Tis.
or
Radical radiotherapy ± neoadjuvant/adjuvant chemotherapy
2. Neoadjuvant chemotherapy for bulky or high risk disease.
3. Node dissection / excision of Obturator / Iliac Nodes up to Bifurcation (The lymphnode
node harvest should be more than 15).
4. Urethrectomy at the time of Cystectomy or Interval Urethrectomy must be considered
when Bladder reconstruction not undertaken.
5. In women Radical Cystectomy must include total Hysterectomy and Oophrectomy in
post menopausal patients. Note: women tend to have a worse prognosis.
3.7.3 Urinary diversion after radical cystectomy
Bladder reconstruction:
 Treatment is recommended at centres with experience in the major types of diversion
techniques. These operations should be centralized to departments doing
cystectomies on a regular basis.
 Patients planned for cystectomy should be informed of the possible alternatives, and
the final decision has to be based on a consensus between patient and surgeon/urooncology CNS/stomatherapist.
 Contra-indications to more complex procedures are debilitating neurological and
psychiatric illnesses, short life expectancy and impaired liver or renal function.
 Patients undergoing continent urinary diversion have to have the motivation and skill
to learn self-catheterization.
 Contra-indications to orthotopic bladder substitutes are TCC of the prostatic urethra,
widespread CIS, high-dose pre-operative irradiation, complex urethral stricture,
intolerance to incontinence or inability to perform ISC.
MVCN: Continent diversion with orthotopic bladder is offered by Mr Manoah Pancharatnam
and Mr Greg Boustead and undertaken at the Lister centre.
3.7.4 Ileal conduit
 The ileal conduit is a reliable treatment option with established efficacy.
 Risks include 20% of patients develop stomal complications and 30% of the
renal units become dilated.
 The disadvantage of the ileal conduit is mainly cosmetic.
3.8 Treatment: Definitive Radiotherapy
Two types of patients with bladder cancer must be discriminated from each other when
comparing survival after radiotherapy with survival after total cystectomy.


Patients who are candidates for total cystectomy, but who are offered primary
radiotherapy for bladder preservation, with salvage cystectomy in case of persistent
disease. No modern trial has so far compared this strategy with primary total
cystectomy.
Patients in whom total cystectomy is not a therapeutic option either due to locally
advanced disease (T4b, eventually T3B) or high age, major co-morbidity and/or
decreased performance status. Furthermore, results from curatively intended
radiotherapy must be differentiated from those associated with palliative therapy.
24
3.8.1 External beam radiotherapy
 The target field usually comprises the bladder only, with a safety margin of 1.5-2 cm,
considering unavoidable organ movements. Any beneficial effect with larger pelvic
fields has not been demonstrated. The target dose for curative radiotherapy of bladder
cancer is 60-66 Gy, with a subsequent boost using external radiotherapy or interstitial
brachytherapy. The daily dose is usually 1.8-2 Gy, and the course of radiotherapy
should not extend beyond 6-7 weeks (1,2) to minimize the re-population of cancer
cells.
 The overall 5-year survival rates in patients with muscle-invasive bladder cancer are
approximately 40-60%, with bladder-cancer-specific survival between 35% and 40%,
with a local recurrence rate of approximately 30%. Based on older trial results, a
recent Cochrane analysis (3) suggested an overall survival benefit with radical surgery
versus radical radiotherapy in patients with muscle-invasive bladder cancer.
 As well as the T category, important prognosticators for the outcome of radiotherapy
include tumour size, presence of hydronephrosis, completeness of pre-radiation,
transurethral resection of bladder tumour (TURB) and complete response to
radiotherapy (4). Using modern standard radiotherapy techniques, major, radiationrelated, late morbidity from the bladder and the bowel is less than 5% in tumour-free
patients.
3.8.2 Interstitial brachytherapy
Patients with small T1/T2 tumours can be treated by implantation of radioactive sources
(caesium, iridium) combined with external radiotherapy and bladder-preserving surgery (5).
The reported survival rates range from 60-80%, depending on the T category.
3.8.3 Radiotherapy and chemotherapy
Clinical studies of cisplatin-based chemotherapy combined with radiotherapy have
demonstrated response rates of 60-80% with 5-year survival rates of 50-60% (7-11)
Bladder preservation seems possible in 50% of patients. However, no definitive long-term
results from randomized studies are available.
3.8.4 Radiosensitizers
Previous attempts to combine radiotherapy of the bladder with hyperbaric oxygen or
misonidazole have not been successful, partly due to technical difficulties. More promising
results have been obtained with a combination of accelerated radiotherapy with carbogen
(ARCO) or carbogen nicotinamide (ARCON) (12,13), with approximately 60% 3-year survival
rates as compared with approximately 30% after radiotherapy alone (12)
3.8.5 Palliation Radiotherapy
Uncontrollable symptoms due to large bladder tumours (haematuria, urgency, pain) can be
palliated by radiotherapy of short duration (7 Gy x 3; 3-3.5 Gy x 10) (14). However, such a
fractionation pattern increases the risk of acute intestinal morbidity, including diarrhoea and
abdominal cramps.
3.8.6 Guidelines
 Modern 3D-radiotherapy, with- or without chemotherapy or radiosensitizers, is a
reasonabletreatment option in patients who wish to preserve their bladder
 The requirements for success of such a strategy are:
 A multidisciplinary approach within the responsible institution, involving co-operation
between the urologist, radiotherapist, medical oncologist and pathologist
25

A regular follow-up schedule in order to perform salvage cystectomy in patients with
recurrent disease as soon as possible
3.9 Treatment: Systemic Chemotherapy
3.9.1 Introduction
 Following cystectomy for muscle invasive bladder carcinoma, up to 50% of patients
may develop metastases. Five-year survival rates of 36-54% have been reported in
cystectomy series from major academic centres (1-4). For high-risk patients with pT3pT4 and/or pN+M0 bladder cancer, the 5-year survival rate is only 25-35%. One-third
of patients relapse in the pelvis alone, but most patients relapse in distant sites.
Response rates of 40-70% have been seen with cisplatin-containing combination
chemotherapy regimens. This level of response has led to their use for locally invasive
disease in combination with cystectomy or radiotherapy, either as neo-adjuvant or
adjuvant therapy.
3.9.2 Neo-adjuvant chemotherapy
 Neo-adjuvant chemotherapy is intended for patients with operable stage T2-T4a
muscle-invasive disease. Chemotherapy is given prior to cystectomy or radiation
therapy to improve the survival rate in patients by treating micrometastatic disease.
It has also been used in some programs to preserve the bladder. Systemic therapy
is delivered early when the burden of metastatic disease is minimal, and is better
tolerated prior to surgery or radiation. Neo-adjuvant therapy has less toxicity in
patients with metastatic disease, since patients generally have a better performance
status and localized disease.

Neo-adjuvant chemotherapy trials show either a trend towards a small benefit or no
benefit. It is possible that the majority of trials may not have enlisted sufficient
numbers of patients to detect statistically significant differences in survival.

Two large recent meta-analysis of neo-adjuvant chemotherapy trials shows a 5-8%
survival advantage at 5years. 9.3 Neo-adjuvant chemotherapy and bladder
preservation.

Selected patients with invasive bladder tumours after neo-adjuvant chemotherapy
may preserve their bladders. Bladder preservation may be possible with an
integrated approach using chemotherapy and radiotherapy. This combination is
capable of producing 5-year survival rates between 42% and 63%, with organ
preservation in approximately 40% of patients. Prognostic factors for local curability
are small tumour size, absence of hydronephrosis, papillary histology, visible
complete TURB and a complete response to induction chemotherapy. Randomized
trials are needed to confirm these results.
3.9.3 Adjuvant chemotherapy
 Several trials with combination chemotherapy appeared to show a difference in favour
of chemotherapy. However, the results are controversial because of the small sample
size and confusing analyses and methodology. (11).
 The EORTC together with several other international groups have begun a large
adjuvant trial that will enlist 1,344 patients worldwide. The study will evaluate four
cycles of immediate chemotherapy versus therapy at the time of relapse in high-risk
26
patients with pT3-pT4 or node-positive disease. Three different chemotherapy
regimens are permitted: MVAC, high-dose MVAC (HD-MVAC), and gemcitabine plus
cisplatin (GC). (12-14).
3.9.4 Metastatic disease
3.9.4.1 Chemotherapy protocols
Two prospective randomized trials have proven the superiority of MVAC (methotrexate,
vinblastine, adriamycin and cisplatin) over single-agent chemotherapy (15,16). Unfortunately,
the use of cisplatin-based combination chemotherapy is associated with long-term survival in
only approximately 15-20% of patients. The median survival duration is only 13 months.
Long-term survival is attained in approximately 15% of patients with metastases in visceral
sites and in 30% of those with nodal disease. Other therapeutic options and strategies are
clearly needed.
The EORTC GU Group has compared a 2-weekly schedule of HD-MVAC to standard MVAC
(13). A statistically significant difference in terms of complete remission rate and progressionfree survival in favour of HD-MVAC was observed. Although no difference in median survival
was seen, an increase in 2-year survival was observed. All the survival curves diverged in
favour of the HD-MVAC treatment arm. However, this finding may have been due to the small
number of patients in the tails of the curves.
Novel chemotherapeutic agents, such as gemcitabine and the taxanes, are among the most
interesting therapeutic options currently available (17). In an international trial, MVAC was
compared to GC (14). The overall survival rate was similar in both arms, as was time to
progressive disease, time to treatment failure, and response rate.
More GC patients than MVAC patients had grade 3/4 anaemia and thrombocytopenia.
More MVAC patients than GC patients had grade 3/4 neutropenia, neutropenic fever,
grade 3/4 mucositis and alopecia. Quality of life was maintained during treatment in both
arms. GC appeared to have a reduced toxicity profile compared to MVAC. This study was
not statistically powered to reveal equivalence in terms of survival to MVAC, nor has GC
been compared to HD-MVAC. Nonetheless many clinicians have begun to use GC as
another standard regimen.
27
The combination of gemcitabine and taxol has been shown to be highly effective in
patients who have failed prior MVAC (18). When cisplatin, gemcitabine and taxol
were given to untreated patients, high overall response rates were observed (19).
The triplet is being compared to GC by the EORTC.
3.9.4.2 Prognostic factors
Prognostic factors that predict response to chemotherapy include alkaline
phosphatase, age greater than 60 years, performance status and visceral
metastases (16,20,21). Independent poor prognostic factors are Karnofsky
performance status less than 80% and the presence of visceral (lung, liver, bone)
metastases (21). Median survival times varied from 9 months in patients with two
poor prognostic factors, to 13 months with one poor prognostic factor, and 33
months with no poor prognostic factors (p = 0.0001). For this reason, phase II
trials can only reveal if a treatment is active or not, and if feasible or not. Careful
prognostic factor analyses are important, but phase III randomized trials are
more reliable as they tend to stratify patients according to the number of risk
factors to avoid imbalance in treatment arms.
More recently, significant interest has developed in molecular markers, such as
p53, Rb and p21, to help optimize therapy and predict chemosensitivity (22).
3.9.5 Guidelines on Chemotherapy
 Cisplatin-containing combination chemotherapy has resulted in complete
remissions in 40-70% ofpatients, with cures in selected cases MVAC and GC
are both used as up-front chemotherapy for metastatic disease. Median
survival is12-14 months.
 A minimal survival benefit has been shown with neo-adjuvant chemotherapy
before cystectomy or radiotherapy.
 Neoadjuvant chemotherapy in combination with radiotherapy for the purpose
of bladder preservation is an investigational approach.
 Convincing data are not yet available on the benefits of adjuvant
chemotherapy. Results of randomized adjuvant trials are pending
3.10. Follow-Up: After Treatement with Curative Intent
3.10.1 Rationale for follow-up:
 To detect local recurrence and distant metastases as early as possible to
permit additional treatment when indicated and if possible. Such therapy may
include salvage cystectomy, urethrectomy, nephro-ureterectomy and or
systemic chemotherapy with and without secondary surgery for residual
tumor.
 Complications of urinary diversion should be recognized early on and
corrected if possible.
Follow-up Procedures
3.10.2 Cystectomy
The first assessment is at 3 months postoperatively and includes :
 Physical examination to exclude surgical complications.
 Serum creatinine and blood gas analysis to assess kidney function
 Urine analysis.
 Sonography of the kidney, liver and retroperitoneum.
28


Chest-X-ray In case of unremarkable findings regular follow-up in intervals of
4 months are indicated.
In case of pN+additional regular CT scans and bone scintigraphy are
necessary. PTis patients need regular assessment of the upper urinary tract.
Check Cystoscopy 6 monthly for 5 years minimum and Urine Cytology after 5
years in patients who have had bladder reconstruction (Orthotopic Bladders).
3.10.3 Radiotherapy
The first assessment is at 3 months post-radiotherapy and includes:
 Physical examination to exclude surgical complications.
 Serum creatinine and blood gas analysis to assess kidney function.
 Urine analysis
 Sonography of the kidney, liver and retroperitoneum
 CT scan of the pelvis
 Cystscopy and urine cytology
 Chest-X-ray The main interest during follow-up remains the bladder, because
of the high local failure rate.
29
4. Non muscle invasive (Superficial) Bladder TCC
4.1 Background
4.1.1 Introduction
Approximately 75–85% of patients with bladder cancer present with disease that is
confined to the mucosa (Ta or CIS) or submucosa (T1) i.e. is non-muscle invasive
bladder cancer (NMIBC). The European Association of Urology (EAU) have recently
published updated guidelines for management.(1)
NMIBC has a high recurrence rate; risk tables from the European Organization for
Research and Treatment of Cancer (EORTC) (2)indicate a 31% (95% CI 24–37%)
probability of recurrent disease at 5 years for low-risk NMIBC. This rises to 62%
(95% CI, 58–65%) in intermediate-risk disease and 78% (95% CI, 73–84%) in highrisk disease. Rates may be lower now that post TURB chemotherapy or BCG
immunotherapy are being given more often.
Tumour multiplicity, size (diameter ≥ 3 cm) and previous recurrence rate are cited as
the most significant factors for determining the risk of recurrence.
4.1.2 Referral Process
The referral process is shown in diagrammatic form below:
4.1.2.1 Referral guideline for haematuria or suspicion of bladder cancer
(modified by TMcN from joint BAUS/Renal Association guideline).


GP refers suspected cases via faxed referral for 2 week appointment.
Clinicians take responsibility for vetting referrals appropriately as two week
waits.
30


Preferential referral of VISIBLE haematuria directly to haematuria clinics with
access to for flexible cystoscopy and imaging.
Cases detected via other pathways fast tracked directly for flexible
cystoscopy.
4.1.2.2 Specialist teams:
Specialist teams for NMIBCa (“superficial bladder cancer”) with cancer nurse and
multidisciplinary support are available within the Cancer network at Lister, Hemel and
Luton & Dunstable hospitals.
These teams manage NMIBC locally. They have the full range of therapies for
NMIBca available and will refer to the surgeons offering specialist surgery for high
risk patients (and for those developing more advanced disease if they progress)
Lister Hospital:
Prof TA McNicholas
Mr DC Hanbury
Mr G Boustead
Mr J Adshead
Mr T Lane
Mr J Bycroft (Oct 2011)
Watford Hospital:
Mr M Pancharatnam
Mrs A Ruston
Mr A Thurston
Mr F Banks
Luton & Dunstable hospital:
Mr A Alam
Mr Taneja
Mr Saleemi
Mr Khan
4.1.2.3 Referral pathway for high risk patients (and for those developing more
advanced disease):
To SMDT for review
To surgical teams offering specialist surgery at Lister Hospital
Mr G Boustead
Mr M Pancharatnam
Mr J Adshead
Mr T Lane
To Clinical oncology teams offering radiotherapy and chemotherapy
Dr R Hughes
Dr Alonso
4.1.3 Multidisciplinary Team Meeting discussion
 All new bladder tumour diagnoses should be reviewed at MDT and a
management plan agreed.
 Pathology review of all high risk cases should occur or if radical therapy is
planned. Such patients should be referred to the SMDT.
 GP’s are informed within 24 hours of MDT/SMDT decisions.
31
4.2. Classification
The tumour node metastases (TNM) 2002 classification, updated in 2009 and
approved by the union International Contre le Cancer (UICC) is widely accepted
(Table1).
Table 1: 2002 TNM classification of bladder cancer
T – Primary tumour
TX primary tumour cannot be assessed
T0 no evidence of primary tumour
Ta Non invasive papillary tumour
Tis carcinoma in situ: ‘flat tumou
T1 tumour invades subepithelial connective tissue
T2 tumour invades muscle
T2a tumour invades superficial muscle (inner half)
T2b tumour invades deep muscle (outer half)
T3 tumour invades perivesical tissue:
T3 microscopically
T3b macroscopically (extravesical mass)
T4 tumour invades any of the following: prostate, uterus, vagina, pelvic wall,
abdominal wall
T4a tumour invades prostate, uterus or vagina
T4b tumour invades pelvic wall or abdominal wall
N – Lymph nodes
NX
N0
N1
N2
N3
regional lymph nodes cannot be assesses
No regional lymph node metastasis
Metastasis in a single lymph node in the true pelvis
(hypogastric, obturator, external iliac, or presacral)
Metastasis in multiple lymph nodes in the true pelvis
(hypogastric, obturator, external iliac, or presacral)
Metastasis in a common iliac lymph node(s)
M – Distant metastasis
MX distant metastasis cannot be assessed
MO no distant metastasis
M1 distant metastasis
4.2.1 Histological grading of superficial bladder tumours
In 1998, a new classification of non-invasive urothelial tumours was proposed by
The World Health Organisation (WHO) and the International Society of Urological
Pathology (ISUP) (1998 WHO/ISUP classification). This new classification system
was published by the WHO in 2004 (table 2).
4.2.1.1 WHO/ISUP grading
The PUNLMP are lesions that do not have cytological features of malignancy but
show normal urothelial cells in a papillary configuration. Although they have a
negligible risk for progression, they are not completely benign and still have a
tendency to recur. Advice is to discuss each case as MDT and decide on
requirement for surveillance cystoscopy.
32
Table 2:
1973 WHO grading
Urothelial papilloma:
Grade 1: well differentiated
Grade 2: moderately differentiated
Grade 3: poorly differentiated
2004 WHO grading
Flat lesions:
Hyperplasia (flat lesion without atypia or papillary)
Reactive atypia (flat lesion with atypia)
Atypia of unknown significance
Urothelial dysplasia
Urothelial CIS
Papillary lesions:
Urothelial papilloma (a completely benign lesion)
Papillary urothelial neoplasm of low malignant potential (PUNLMP)
Low-grade papillary urothelial carcinoma
High-grade papillary urothelial carcinoma
The 2004 WHO grading classifies papillary urothelial neoplasms into only two
grades: low grade and high grade (Table2). The use of 2004 WHO classification is
advocated, as this may result in a uniform diagnosis of tumours, which is better
stratified according to risk potential. However, until the 2004 WHO classification has
been validated by more clinical trials, tumours should be graded using both the 1973
and the 2004 WHO classifications. Most clinical trials published to date on TaT1
bladder tumours have used the 1973 WHO classification.
4.2.2. Inter and intra-observer variability in staging and grading
Despite well-defined criteria for the diagnosis of urothelial carcinoma, there is
significant variability among pathologists on defining dysplasia and CIS. There is also
important inter observer variability in classifying stage T1 versus Ta tumours and
grading tumours. Therefore joint review at MDT is mandatory and where doubt
exists, patients should be considered for 2nd look TURBT approximately 6 weeks
after initial resection.
4.3 Risk Factors
 Previous occupational exposure from the following industries: printing: iron
and aluminium processing, industrial painting, gas and tar manufacturing.

Cigarette smoking triples the risk of developing bladder cancer. Smoking
leads to higher mortality from bladder cancer during long term follow up, even
though in a multivariate analysis the prognostic effect of smoking was weaker
that that of other factors, such as stage, grade, size and multi focality of the
tumour.
4.4 Diagnosis
4.4.1 Symptoms of TaT1 bladder tumours
Visible or invisible (urine dip stick test +ve) Haematuria are the most common
findings in TaT1 bladder tumours. TaT1 tumours do not cause bladder pain and
33
rarely present with bladder irritation, dysuria or urgency. In patients who do complain
of these symptoms, CIS should be suspected.
4.4.2 Physical examination
Physical examination will not reveal a bladder tumour confined to the mucosa or sub
mucosa (TaT1).
4.4.3 Imaging
4.4.3.1 Intravenous urography
Large tumours may be seen as filling defects in the bladder. Intravenous urography
(IVU) or CT-IVU are used to look for filling defects in the calyces, renal pelvis and
ureters and hydronephrosis, which may indicate the presence of a upper urinary tract
tumour. The necessity to perform routine IVP/CT-IVU once a bladder tumour has
been detected is now questioned because of the low incidence of significant findings
in the upper urinary tract. The incidence of upper urinary tract tumours is low in lowgrade tumours, but increases to 7% in T1G3 tumours.
4.4.3.2 Ultrasonography
Ultasonography (US) has been used with increasing frequency as the initial tool to
assess the urinary tract. This is not only because it avoids radiation exposure and
the use of contrast agents, but also because sensitive transducers have improved
imaging of the upper urinary tract and bladder. Transabdominal US permits
characterization of renal masses, detection of hydronephrosis and visualization of
intraluminal filling defects in the bladder. Combined with plain abdominal film, it can
be as accurate as IVU in the diagnosis of the cause of haematuria.
4.4.3.3 Cross Sectional imaging
Patients found to have high risk superficial bladder cancer should have an MRI or CT
scan (if not already performed) to detect possible muscle invasion or occult
metastases. High risk patients include:




T1G3 tumours
CIS/pTis
Tumours >3cm
Multifocal or bulky superficial tumours
4.4.4 Urinary cytology
Voided urine cytology is useful when a high-grade malignancy or CIS is present.
Positive urinary cytology may indicate urothelial tumour anywhere in the urinary tract,
from the calyx, through the ureters, into the bladder and urethra. Moreover, negative
voided urinary cytology does not exclude the presence of a low-grade bladder
tumour. Cytological interpretation can be problematic; low cellular yields, atypia,
degenerative changes, urinary tract infections, stones and intravesical instillations
hamper a correct diagnosis.
4.4.5 Urine molecular tests
Many studies have focused on evaluating molecular urinary markers. Tests for
bladder tumour antigen, nuclear matrix protein 22 (NMP 22), fibrin-degradation
products, UroVysion and ImmunoCyt are promising. Most of these tests have a
better sensitivity for detection bladder cancer, but specificity is lower. Hence falsepositive tests can lead to unnecessary investigation. It remains unclear whether
these tests offer additional information which is useful for decision making, treatment
34
and prognosis of superficial bladder tumours, as data from large prospective multi
centre trials are lacking.
4.4.6. Cystoscopy
The diagnosis of bladder cancer ultimately depends on cystoscopic examination of
the bladder and histological evaluation of the resected tissue. In general, cystoscopy
is initially performed in the Endoscopy room, Day case theatre or suitably equipped
outpatient room, using flexible instruments. Many older men tolerate this procedure
well using skill, gentleness and local anaesthetic urethral gel. Younger men usually
need intravenous sedation. If a bladder tumour has been visualized in earlier
imaging studies or if urinary cytology has previously been found to be positive,
diagnostic cystoscopy can be omitted and the patient listed directly for definitive
resection (TURBT) usually under GA or spinal anaesthesia during a hospital
admission.
4.4.7 Transurethral resection of TaT1 bladder tumours
Small tumours can be resected in one chip where the chip contains the complete
tumour plus a part of the underlying bladder wall. Larger tumours have to be
resected in fractions. First, the exophytic tumour tissue is removed, then separately
the underlying bladder wall is resected or biopsied into the muscle. Without the
presence of muscle, the pathologist is unable to stage the tumour as Ta, T1 or T2. In
the case of large tumours, the surgeon should resect the edges of the resection area
separately, or take “cold cup” biopsies of adjacent mucosa as CIS may be present
there. The tissue from the different areas have to be sent in separate containers to
facilitate pathological assessment. Cauterization of the removed tissue should be
minimised to prevent tissue destruction which hampers correct staging and grading.
A complete and correct TUR is essential for the prognosis of the patient.
4.4.8 Bladder biopsies
Bladder tumours are often multifocal. Carcinoma in situ, dysplasia, inflammation,
etc., may present themselves as velvet-like, reddish areas in the bladder or may be
not visible at all. With papillary tumours, if the rest of the bladder mucosa has a
normal appearance and if urine cytology is negative, routine random biopsies should
not be performed. The likelihood of detecting CIS is extremely low and the choice of
adjuvant intravesical therapy is not influenced by the biopsy result.
However, when cytology is positive or when abnormal areas of urothelium are seen,
it is advised to take the ‘cold cup’ biopsies. These biopsies should be sent for
pathological assessment in separate containers. Biopsies of the prostatic urethra
should to be taken when a tumouris located on the trigone or bladder neck, if CIS is
suspected, or when cytology is positive in the absence of visible tumour..
4.4.9 Fluorescence cystoscopy (“blue light cystoscopy”)
As a standard procedure, cystoscopy and TUR are performed using white light.
Fluorescence cystoscopy, which is performed using blue light and a porphyrin-based
photosensitizer, (hexi)-aminolaevulinic acid (HAL or ALA), may reveal areas in the
bladder that are suspicious for CIS or for developing papillary tumour that cannot be
seen with white-light cystoscopy. A recent prospective, randomised, multi-
institutional study found no clinical advantage of fluorescence cystoscopy compared
with white light cystoscopy and TUR.(3) Blue light cystoscopy may be useful in
patients with persistently positive cytology in a normal appearing urinary tract.
Centres are available within the network to cross refer to if this is necessary.
Centres with Fluorescence cystoscopy:
35
Expected to be available at the Lister specialist centre within the next six months.
Until such time as it is available within network, referrals are to Colin Bunce at Barnet
4.4.10 Second resection
The presence of residual tumour after initial TURBT has been reported in up to 40%
of patients. A re-TUR should be performed when the initial resection has been
incomplete, e.g when multiple and/or large tumours are present or when the
pathologist has reported that the specimen contains no muscle tissue. Furthermore,
a re-TUR should also be performed when a TaT1, high grade tumour has been
detected at the initial TUR. The likelihood that a TaT1G3 tumour has been
understaged and therefore a muscle-invasive tumour has been missed is ±10%. As
the treatment of a TAT1G3 tumour and a T2 tumour may be completely different,
correct staging is important. It has been demonstrated that a second TUR leads to
improved recurrence free survival.(4) There is no consensus about the timing of a
second TUR, but most procedures are done between 2 and 6 weeks after the initial
TUR.
4.5 Adjuvant Treatment
4.5.1 One, immediate, post-operative instillation
Although a state-of-the-art TUR by itself should eradicate a Ta, T1 tumour
completely, these tumours will recur in a high percentage of cases (31% probability
of recurrent disease at 5 years for low-risk NMIBC, 62% in intermediate-risk disease
and 78% in high-risk disease) and progress to muscle-invasive bladder cancer in a
limited number of cases. The high variability in the 3 month recurrence rate
(evidence of tumour at cystoscopy 3 months after TUR) indicates that TUR is
incomplete or provokes recurrences in a considerable percentage of patients.
It is therefore recommended that every patient with apparently superficial looking
bladder cancer be considered for adjuvant intravesical chemotherapy.
A meta analysis of seven randomized trials (1,476 patients with a median follow-up of
3.4 years) has demonstrated that one immediate instillation of chemotherapy after
TUR decreases the relative risk of recurrence by 40%.(5) Both single and multiple
tumours benefit from a single instillation only. A more recent study confirmed a
benefit but only in primary and single tumours.(6) In summary, one immediate
instillation of chemotherapy significantly reduces the risk of recurrence of TaT1
bladder cancer. For patients at low risk of recurrence ONE immediate instillation is
sufficient. Further studies are required to determine the definitive role of immediate
chemotherapy before BCG, or further chemotherapy instillations in intermediate- and
high-risk groups.(1)
The timing of the instillation is crucial. In most studies, the instillation was
administered within 24 hours. Administration after 24 hours may not be beneficial.
(7, 8)There is no superior drug with regard to efficacy. Mitomycin C, epirubicin and
doxorubicin have all shown a beneficial effect. An immediate instillation should NOT
be given where intra-or extra peritoneal perforation is seen or strongly suspected,
which is most likely in extensive TUR procedures.
4.5.2 Additional adjuvant intravesical instillations
The need for further adjuvant intravesical therapy depends on the prognostic risk of
the superficial bladder tumours
The choice between chemotherapy or immunotherapy largely depends on the risk
that needs to be reduced ie recurrence or progression.
36
Recurrence: Single adjuvant chemotherapy bladder instillations are effective in
preventing recurrence in low-grade tumours. Meta-analyses have demonstrated
reduced recurrence rates in primary and recurrent tumours but not reduced risk of
progression.(9-11) Bacillus Calmette-Guerin (BCG) immunotherapy with
maintenance therapy has proven to be superior to intravesical chemotherapy in
reducing recurrences. A 2009 meta-analysis indicated a 32% reduction in the risk of
recurrence was found for BCG compared with MMC (p < 0.0001), whereas BCG
without maintenance was less effective than MMC). (12)
Progression: Two earlier meta-analyses demonstrated that BCG with maintenance
therapy prevents, or at least delays, tumour progression.(13, 14) The EORTC metaanalysis demonstrated a reduction of 27% in the odds of progression with BCG
maintenance treatment ( p = 0.0001).(14) On the contrary, the 2009 meta-analysis of
individual patient data was unable to confirm any statistically significant difference
between MMC and BCG for progression, survival, and cause of death.(12) The EAU
guideline concludes that, despite these conflicting results, most of the data were able
to show a reduction in the risk of progression in tumours with high and intermediate
risk if BCG (including a maintenance schedule of at least 1 year) was used.
4.5.3 Intravesical BCG instillation (immunotherapy)
4.5.3.1 Indications for BCG
The use of BCG will not alter the natural course of disease in low risk patients
(approx. 50% of cases) and may be considered to be over treatment.
In patients at high risk (approx. 15% of cases) e.g. multiple T1G3 tumours, Ta-T1G3
tumours with or without CIS, and CIS alone, where 15% or more of the patients will
progress, BCG is indicated: the advantages of intravesical BCG are more
pronounced than for intermediate risk patients, who are at a lower risk of
progression.
The treatment of this remaining intermediate risk tumours (multifocal T1G1, TaG2
and single T1G2 tumours) is more controversial. It consists of complete TUR
followed by intravesical chemotherapy or intravesical BCG. The major issue in
intermediate risk tumours is to prevent recurrence and progression, of which
recurrence is by far the most likely. Millan-Rodriguez et al. found that, while tumour
will recur in about 45% of these patients, the likelihood of progression to muscleinvasive disease is low in these patients at approximately 1.8%. In Section 5.4 the
calculation of risk for tumour recurrence and progression,both short and long term,
are explained.
4.5.3.2. BCG toxicity
Assuming that maintenance therapy is necessary for optimal efficacy, the issue
Of BCG toxicity becomes more relevant. Due to the more pronounced side effects of
BCG compared to intravesical chemotherapy, reluctance still exists about BCG use.
BCG should only be given by trained nurses in unit performing significant numbers of
treatments on a regular basis and experienced in recognizing and managing
complications.
4.5.3.3 The optimal schedule for BCG
Induction BCG instillations are classically given according to the empirical 6 weekly
induction schedule introduced by Morales 30 years ago. However, many different
maintenance schedules have been used, ranging from a total of 10 instillations given
in 18 weeks, to 30 instillations given for 3 years. The optimal number of induction
37
instillations and the optimal frequency and duration of maintenance instillations
remain unknown.
4.5.3.4 The optimal dose of BCG
To reduce BCG toxicity, a number of authors have proposed one third and one
quarter dose instillations of BCG. Further research is required to determine the
optimal dose of BCG, both for induction instillations and for maintenance.
4.5.3.5 Recommendations for use of BCG
 BCG is superior to chemotherapy for preventing recurrences.
 Intravesical BCG is superior to chemotherapy in terms of complete response
and disease-free survival. However, there is no conclusive evidence that one
agent is superior in terms of overall survival.(15)
 Patients with intermediate risk and high risk tumours are suitable for BCG
therapy.
 BCG delays, or prevents, progression to muscle invasive bladder cancer.
 Maintenance therapy is necessary for optimal efficacy.
 The optimal schedule and dose have not yet been determined.
 At least 1 year of maintenance therapy is advised.
4.5.4 Predicting recurrence and progression in TaT1 tumours
The classic way to categorize patients with Ta/T1 tumours into risk categories is to
use prognostic factors derived from multivariate analyses. In such a way, it is
possible to dividepatients into low risk (50%), intermediate risk (35%) and high risk
(15%) groups. When using these risk groups. However, no separation is made
between the risk of recurrence and progression. Although prognostic factors may
indicate a high risk for recurrence, the risk of progression may still be low and other
tumours may have a high risk for both recurrence and progression.
In order to separately predict the short term and long term risks of both recurrence
and progression in individual patients, the EORTC developed a scoring system and
risk tables. The basis for these tables is the EORTC database which provided
individual patient data for 2,596 patients diagnosed with T1/T1 tumours who were
randomised in seven EORTC trials.
The scoring system is based on the six most significant clinical and pathological
factors:






Number of tumours.
Tumour size.
Prior recurrence rate
T Category
Presence of CIS
Tumour grade
The probability for recurrence and progression at 1 year varied from 15-61% and 0.2-17%
respectively. After 5 years of follow up, recurrence and progression rates ranged from 31%
to 78% and from 0.8-45% respectively (see Tables from EAU guideline update 2011. Babjuk
M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou-Redorta J, et al. EAU guidelines
on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol. 2011
Jun;59(6):997-1008).
38
Table 2: Weighting used to calculate recurrence and progression scores
39
Note: electronic calculators for Tables 3 and 4 are available at
http://www.eortc.be/tools/bladdercalculator/
The use of electronic versions of these tables is recommended. The urologist can
discuss the various options with the patient. Which may range from one postoperative instillation of chemotherapy only, adjuvant intravesical chemotherapy,
adjuvant intravesical BCG, or in the high risk cases, cystectomy.
4.5.4.1 Recommendations for intravesical chemotherapy or BCG
immunotherapy
 Patients at low to moderate risk of recurrence and very low risk of
progression, a single immediate dose of chemotherapy is strongly
recommended as the complete adjuvant treatment.

Patients at low to moderate risk of progression, regardless of risk of
recurrence, a single immediate post operative dose of chemotherapy should
be followed by either more chemotherapeutic instillations for a duration of at
least 6 – 12 months (maintenance) or intravesical BCG instillations for at least
1 year (maintenance).
Patients at high risk of progression, intravesical BCG (at least 1 year of maintenance)
or immediate radical cystectomy should be discussed.
40
4.5.5. Treatment of failures of instillation therapy
The treatment can be considered to fail when:



Higher grade of T category or carcinoma in situ (CIS) appear during therapy.
If a recurrence (even of the same grade and T category) is present at both 3
months and 6 months, the therapy can also be considered to be a failure
because only a few patients will respond to further intravesical therapy.
Recurrence at 3 months is not considered to be a failure because additional
treatment provokes complete remission in about one-fifth of patients.
Changing from BCG to chemotherapy can give further remissions in selected cases.
Intravesical chemotherapy with either Mitomycin C or Epirubicin would be an option
for those patients failing or who are unsuitable for BCG therapy.(15)
Patients failing BCG are at high risk for progression. Considerable time can be lost in
giving alternative treatment and in the majority of patients cystectomy is advised
because of the high risk of development of muscle invasive tumour and metastases
at this stage of the disease.
The time to response to intravesical immunotherapy is not clear. Delaying
cystectomy might lead to progression, metastases and death from bladder cancer.
Patients with no response to BCG at 6 months after starting BCG should be
considered for radical cystectomy and referred to the SMDT.
Where new superficial tumours appear every 3 months, the consequent TUR, the
ongoing intravesical instillations, etc., may lead to a bladder of such low quality terms
of capacity, urge, pain and quality of life, that, in selected cases, a patient should
consider a cystectomy.
4.5.6 Recommendations for follow up cystoscopy for TaT1 bladder cancer
 All patients have a check cystoscopy at 3 months with review of risk status at
that point.
 Patients with low risk (TaG1) tumours (50% of all patients) should have a
cystoscopy at 3 months. If negative, the following cystoscopy is advised at 9
months and consequently yearly for 5 years.
 High risk patients (15% of all patients) should have a cystoscopy at 3 months.
If negative the following cystoscopies should be repeated every 3 months for
a period of 3 years, every 4 months in the third year, every 6 months
thereafter until 5 years and yearly thereafter. Annual or bi-annual IVU should
be performed.
 Patients with intermediate risk factors (about one third of all patients) should
have an in-between follow up scheme, adapted according to personal and
subjective factors.
41
NEW REFERENCES
1. Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou-Redorta J, et
al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder,
the 2011 update. Eur Urol. 2011 Jun;59(6):997-1008.
2. Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis
L, et al. Predicting recurrence and progression in individual patients with stage Ta
T1 bladder cancer using EORTC risk tables: a combined analysis of 2596
patients from seven EORTC trials. Eur Urol. 2006 Mar;49(3):466-5; discussion
75-7.
3. Schumacher MC, Holmang S, Davidsson T, Friedrich B, Pedersen J, Wiklund
NP. Transurethral resection of non-muscle-invasive bladder transitional cell
cancers with or without 5-aminolevulinic Acid under visible and fluorescent light:
results of a prospective, randomised, multicentre study. Eur Urol. 2010
Feb;57(2):293-9.
4. Divrik RT, Yildirim U, Zorlu F, Ozen H. The effect of repeat transurethral resection
on recurrence and progression rates in patients with T1 tumors of the bladder
who received intravesical mitomycin: a prospective, randomized clinical trial. J
Urol. 2006 May;175(5):1641-4.
5. Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate
postoperative instillation of chemotherapy decreases the risk of recurrence in
patients with stage Ta T1 bladder cancer: a meta-analysis of published results of
randomized clinical trials. J Urol. 2004 Jun;171(6 Pt 1):2186-90, quiz 435.
6. Gudjonsson S, Adell L, Merdasa F, Olsson R, Larsson B, Davidsson T, et al.
Should all patients with non-muscle-invasive bladder cancer receive early
intravesical chemotherapy after transurethral resection? The results of a
prospective randomised multicentre study. Eur Urol. 2009 Apr;55(4):773-80.
7. Hendricksen K, Witjes WP, Idema JG, Kums JJ, van Vierssen Trip OB, de Bruin
MJ, et al. Comparison of three schedules of intravesical epirubicin in patients with
non-muscle-invasive bladder cancer. Eur Urol. 2008 May;53(5):984-91.
8. Kaasinen E, Rintala E, Hellstrom P, Viitanen J, Juusela H, Rajala P, et al. Factors
explaining recurrence in patients undergoing chemoimmunotherapy regimens for
frequently recurring superficial bladder carcinoma. Eur Urol. 2002 Aug;42(2):16774.
9. Huncharek M, McGarry R, Kupelnick B. Impact of intravesical chemotherapy on
recurrence rate of recurrent superficial transitional cell carcinoma of the bladder:
results of a meta-analysis. Anticancer Res. 2001 Jan-Feb;21(1B):765-9.
10. Huncharek M, Geschwind JF, Witherspoon B, McGarry R, Adcock D. Intravesical
chemotherapy prophylaxis in primary superficial bladder cancer: a meta-analysis
of 3703 patients from 11 randomized trials. J Clin Epidemiol. 2000 Jul;53(7):67680.
11. Pawinski A, Sylvester R, Kurth KH, Bouffioux C, van der Meijden A, Parmar MK,
et al. A combined analysis of European Organization for Research and Treatment
of Cancer, and Medical Research Council randomized clinical trials for the
prophylactic treatment of stage TaT1 bladder cancer. European Organization for
Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative
Group and the Medical Research Council Working Party on Superficial Bladder
Cancer. J Urol. 1996 Dec;156(6):1934-40, discussion 40-1.
12. Malmstrom PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, et
al. An individual patient data meta-analysis of the long-term outcome of
randomised studies comparing intravesical mitomycin C versus bacillus
Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol. 2009
Aug;56(2):247-56.
42
13. Bohle A, Bock PR. Intravesical bacille Calmette-Guerin versus mitomycin C in
superficial bladder cancer: formal meta-analysis of comparative studies on tumor
progression. Urology. 2004 Apr;63(4):682-6; discussion 6-7.
14. Sylvester RJ, van der MA, Lamm DL. Intravesical bacillus Calmette-Guerin
reduces the risk of progression in patients with superficial bladder cancer: a
meta-analysis of the published results of randomized clinical trials. J Urol. 2002
Nov;168(5):1964-70.
15. Shelley MD, Mason MD, Kynaston H. Intravesical therapy for superficial bladder
cancer: a systematic review of randomised trials and meta-analyses. Cancer
Treat Rev. 2010 May;36(3):195-205.
43
Appendix 1
Referral guideline for haematuria or suspicion of bladder cancer
(modified by TMcN from joint BAUS/Renal Association guideline).
44
5. Prostate Cancer
5.1 Background Information
Cancer of the prostate is now recognised as one of the principal medical problems
facing the male population. In the European Union an estimated 85,000 new cases of
cancer are diagnosed each year. This accounts for 9% of all cancer deaths among men.
In the United Kingdom approximately 25000 new cases of prostate cancer are
diagnosed annually. However the discrepancy between clinical incidence and
pathological prevalence remains an unresolved issue. In the United Kingdom
approximately 60% of cancers present at stages T1 and T2. About 25% are locally
advanced (T3 at presentation) with 15% presenting as metastatic disease. However up
to 40% of patients in stages T1 and T2 will fail local treatment.
Good communication between healthcare professionals and men with prostate cancer is
essential. It should be supported by evidence-based written information tailored to the
man's needs. Treatment and care, and the information men with prostate cancer are
given about it, should be culturally appropriate. It should also be accessible to people
with additional needs such as physical, sensory or learning disabilities, and to people
who do not speak or read English.
If the man agrees, his partner, family and carers should have the opportunity to be
involved in decisions about treatment and care. Families and carers should also be
given the information and support they need.
5.1.1 Urgent referral from GP
Referral process
 Prepared proforma
 Single referral fax number for each Trust
 Referral vetted by clinicians
5.1.2 Indications for referral
 Clinical suspicion of prostate cancer
 Abnormal DRE
 Elevated age-specific prostate specific antigen (PSA)
5.1.3 Diagnosis of suspected prostate cancer
 Patients are offered urgent referral for TRUS guided biopsies of the prostate.
This is offered as a one stop initial prostate clinic in some settings.
 Histological confirmation of cancer is usually confirmed after histological
examination of needle biopsies.
 Incidental cancers will be found in 6-10% of men undergoing routine TURP.
Arrangements for urgent follow-up to explain the diagnosis and arrange
appropriate staging investigations should be made.
 In selected cases, men with significantly elevated PSA levels (multiples of 1001000), clinical/radiological findings suggestive of Ca prostate or where biopsy
might prove hazardous, biopsies may be deemed unnecessary and treatment
initiated without histological confirmation.
45
5.1.4 Discussion at MDT
 All new prostate cancer patients are discussed at MDT
 All recurrent prostate cancer/failed local therapy patients are discussed at MDT
 All hormone refractory patients are discussed at MDT
5.2 Risk Factors
Risk factors for developing clinical carcinoma of the prostate are not well known. Those
which have been identified are:


Heredity – if one first line relative (brother or father) has the disease, the risk is
doubled. The more first line relatives affected the risk increases 5-11 fold. A
small sub population of individuals with cancer (about 9%) are true hereditary,
defined as three or more relatives affected or at least who develop early onset
disease (before the age of 55 years).
Exogenous factors identified include high content animal fat in the diet, low intake
of vitamin E, lignans and iso-flavonoids.
The main diagnostic tools to confirm a diagnosis of carcinoma of the prostate are:
Digital rectal examination (DRE)
Serum prostate specific antigen (PSA)
Transrectal ultrasound scans and needle biopsy of the prostate
5.3 Diagnosis
5.3.1 DRE
The majority of cancer of the prostate located in the peripheral zone may be detected by
DRE when the volume is >0.2cc. Abnormal DRE signifies a 15-40% risk of cancer
depending on the experience of the examiner.
5.3.2 PSA
Determination of PSA level has revolutionised the diagnosis of cancer of the prostate.
However there is no threshold of PSA that indicates the highest risk of prostate cancer
and this needs to be identified. The positive predictive value of PSA is approximately 2535% between a PSA of 4 and 10 and 50-80% for those above 10. In the detection of
non-palpable prostate cancer, age related PSA values should be used i.e. 40-50 years
PSA 2.5, 50-60 years PSA 3.5, 60-70 PSA 5.5 as the upper limit of normal. Free to total
PSA ratios are useful for patients with a PSA between 4 and 10. A free to total ratio of
<15% is an indication for biopsy.
5.3.3 TRUS
Prostate cancer shows a variety of echo patterns on transrectal ultrasound scanning.
Although the classic lesion is a hypoechoic area, larger tumours often appear as a mixed
pattern consisting of hypo and hyper echoic areas. Up to 38% of cancers however are
isoechoic.
46
5.3.4 TRUS biopsies of the Prostate
Ultrasound guided transrectal 18 gauge core biopsies are now the standard method of
obtaining prostate tissue for histopathological examination. Some form of local
anaesthetic block or sedation is recommended, but biopsies can be taken without
Indications for rebiopsy:




High grade PIN on initial biopsy.
Insignificant cancer ie <10% of one core or unable to grade accurately.
Rising total PSA.
Declining free to total PSA ratio.
PCa3 (previously known as uPM3), a new urinary marker for prostate cancer detection
will enter routine use in the near future. Because it entails urine collected after prostatic
massage its role will be limited to selected subsets of patients.
Sedation/anaesthesia. Antibiotic prophylaxis is recommended. Lesion guided biopsies
are used when there is a palpable nodule or abnormal echo area on TRUS. Where the
prostate has a normal ultrasonographic appearance, 10 or 12 core biopsy technique is
recommended. There is evidence that predictable increases in cancer detection rates
would be expected by increasing the number of biopsies beyond six cores ie biopsies of
12-15 cores would increase the proportion of cancer detection between 30-35%.
5.4 Staging
Staging investigations for prostate cancer include:
 DRE
 PSA
 Gleason grade
 MRI/CT
 Nuclear bone scan
Staging investigations for patients being assessed for radical treatment are FBC, U&E,
LFT, PSA, chest x-ray (optional), MRI scan pelvis and abdomen (with or without
endorectal coil enhancement). Isotope bone scan only if the PSA is >15 or Gleason
grade 8, 9 or 10.
Staging investigations for patients being assessed for locally advanced or metastatic
disease. MRI replaced by spiral CT with contrast. Bone scan in all cases.
A number of additional staging techniques may be employed under specific indications
at the request or recommendation of the MDT. These include:



Diagnostic lymphadenectomy
Transrectal ultrasound guided biopsies of seminal vesicles. This may be
indicated in selected patients and may alter the choice of subsequent treatment.
Bone biopsies. This may be indicated in certain high risk patients with isolated
lesions on bone scan. The subsequent treatment may be altered by the outcome
of the bone biopsies.
47
5.5 CLASSIFICATION TNM Staging (UICC 5th edition 1997)
T- Primary Tumour
T1 - Clinically inapparent tumour not palpable or visible by imaging
T1a - incidental histological finding in < 5% of tissue resected
T1b - incidental histological finding in > 5% of tissue resected
T1c - tumour identified by needle biopsy (eg due to raised PSA)
T2 - Confined within prostate
T2a - tumour involves one lobe T2a – one lobe <half
T2b - tumour involves both lobes T2b – one lobe more half
T2c – bilat
T3 - Through prostatic capsule
T3a – extracasular extension (unilateral or bilateral)
T3b - invades seminal vesicle(s)
T4 - Fixed/adjacent structures other than seminal vesicles (bladder neck, external
sphincter, rectum, levator muscles, and/or fixed to pelvic wall)
Regional Lymph Nodes
Metastases
NX nodes cannot be assessed
MX distant metastasis cannot be
assessed
M0 no metastasis
M1 distant metastasis
M1a non regional lymph node(s)
M1b bone (s)
M1c other site (s)
N0 no regional nodes
N1 regional node metastasis
5.6 Treatment Options
Treatment options are discussed under the following headings
6.1 Localised Prostate cancer
6.2 PSA only failure after definitive treatment
6.3 Locally Advanced
6.4 Positive margins after Radical prostatectomy
6.5 Metastatic Prostate cancer
6.6 Hormone refractory prostate cancer
5.6.1 Localised Prostate Cancer
Therapy options depend on patient age, PSA, Gleason score, performance status and
patient choice. Options include:
5.6.1.1 Deferred treatment/watchful waiting/PSA surveillance
5.6.1.2 Radical prostatectomy
5.6.1.3 Radiotherapy
48
 Radical external beam radiotherapy
 Brachytherapy
 Interstitial seed implants
 HDR
5.6.1.4 High Intensity Focused Ultrasound (HIFU) and Cryotherapy
5.6.1.1 Deferred Treatment or Active surveillance
This is used to describe treatment strategies which include an active standpoint to
postpone treatment unless the need arises. In most cases this applies to patients where
the life expectancy is <10 years or those with significant co-morbidity. In selected cases
younger patients with localised disease may choose to withhold treatment with curative
intent if evidence indicates possible latent or non-lethal cancer. Patients require close
follow up with PSA surveillance and occasionally rebiopsy may be indicated.
See active surveillance protocol attached.
Table 2: Outcome of deferred treatment in localized cancer of the prostate in relation to
tumour grade (1)
Percentage of patients (95% confidence interval)
5 Years
10 Years
Disease –specific survival
Grade1
98 (96-99)
87 (81-91)
Grade 2
97 (93-98)
87 (80-92)
Grade 3
67 (51-79)
34 (19-50)
Metastasis Free Survival
Grade 1
93 (90-95)
81 (75-86)
Grade 2
84 (79-89)
58 (49-66)
Grade 3
51 (36-64)
26 (13-41)
Indications for Deferred Treatment
T1a well and moderately differentiated tumours – in younger patients with the life expectancy of
>10 years, restaging with PSA, TRUS and biopsy of the prostatic remnant is recommended.
T1b and T2 well and moderately differentiated tumours with life expectancy of <10 years. Optional
stages of T1b to T2c Gleason 2-6 with life expectancy of 10-15 years and patients not willing to
accept side effects of active treatment or stages T3-T4 asymptomatic patients well and moderately
differentiated cancer and a short life expectancy. Risk of prostate cancer related death is
summarised in Table 1.
Table1: The 15 year risk of dying of prostate caner stratified by Gleason score (men 55-74)
(adapted from Griebling et al, Albertsen et al)
Gleason score
Risk of cancer death
2-4
5
6
7
8-10
6.1.2 Radical Prostatectomy
4-7%
6-11%
18-30%
42-70%
60-87%
Cancer specific
survival
8%
14%
44%
76%
93%
49
Indications
Presumably curable carcinoma prostate with a life expectancy of more than 10 years
stage T1a. Life expectancy 15-20 years or when high grade, any grade IV disease on
biopsy.
Stage T1b or T2 and stage T1C.
Optional stage T3 with limited extra-capsular extension and Gleason grade below 8 and
PSA <20 – should ideally be put into a clinical trial (EORTC).
Contra-Indications
When no survival benefit is expected – life expectancy <10 years.
Stage T1a disease with limited survival expectancy and Gleason score 7 or less or when
there is low probability of cure.
Radical prostatectomy should be performed in centres performing a minimum of 50
major pelvic cases per year as per guidelines.
5.6.1.2 Neoadjuvant hormonal therapy and radical prostatectomy
 Five prospective, randomized studies have shown a decrease in positive surgical
margin rates, with the use of a short-term (6 weeks-4 months) course of NHT.
Follow-up of these randomized trials has indicated that this has not resulted in
any difference in PSA-free failure after 3-5 years of follow-up. Thus far, no data
are available on disease-free or overall survival rates.

With these results in mind, a 3-month course of NHT cannot be recommended
for routine clinical use prior to radical prostatectomy. Further studies on the
duration and type of androgen ablation are needed in order to define its role in
the treatment of localized or locally advanced prostate cancer.
5.6.1.3 Radiotherapy
Clinically Localised Cancer of the Prostate (T1-2NX-M0, NXM0)
Radiation therapy may produce treatment results comparable to those achieved by
radical prostatectomy. This supported by a number of older prospective and
retrospective in which local control was obtained 70-90% of patients (Leeball et al 1984
and Hanks et al 1998). The long term (10-15 year) disease free survival rate for 70-90%
(Pollock et al 1998, Hanks et al 1994).
The options are to consider




brachytherapy alone with a permanent I125 seed implant
external beam treatment alone
external beam in combination with a temporary HDR afterloading
(phase 3 trial)
High dose rate monotherapy alone (phase 2 trial)
plant
Permanent iodine seed implant
Consider if
 T1C/T2
 PSA < 15
 Gleason < 7
 No previous TURP
50


Fit for general anaesthetic
IPSS ideally <12
Procedure
a) transrectal ultrasound volume study is required if the patient fulfills the above criteria.
If the volume is greater than 50ml an implant is contra-indicated. The alternatives at this
point are either to proceed to external beam treatment (or rediscuss surgery) or to have
a 3 month trial of anti-androgen therapy followed by a further transrectal ultrasound
volume study when the volume may be sufficiently small to proceed with an implant.
[LHRH anologue preferred as hormonal cytoreductive agent]
b) implant will be undertaken 4 to 6 weeks after the volume study requiring admission for
general anaesthetic and an overnight stay following the implant. The prescribed dose is
145Gy minimum peripheral dose TG43/NIST99 using 0.37 mCi I
operators are Dr P Hoskin and Dr P Ostler.
125
seeds. Current
External beam alone or external beam with brachytherapy
An external beam component should be considered where there is a significant risk of
extracapsular or seminal vesicle invasion. This is predicted by a PSA >10 or a Gleason
score of 7 or above (Partin et al JAMA 1997; 1445-1451). There is obviously some
overlap in patients who have low Gleason scores but high PSAs and vice versa where
clinical decisions and patient preference must be taken into consideration.
Temporary implant boosts should at present be considered non standard treatment
outside the randomised trial(s) currently underway. In patients who elect to have this
treatment outside of this trial it may be given provided it is understood that there is
currently no data to suggest that it is more effective or less toxic than external beam
treatment alone.
Radical External beam conformal radiotherapy technique
Patients are CT planned (3mm slices) with a comfortably full bladder and using ankle
stocks.
Conformal radiotherapy delivered using MLCs
The following target definition are used:
Gross Target volume (GTV) is prostate. Seminal vesicles to be included in the GTV if
PSA >10, G3 (ie Gleason >=7) or T2b, volume of seminal vesicles is a clinical descision
PTV = GTV + margin as defined below; produced by 3D growing algorithm on ADAC
planning system
Ant border 1cm margin
Post border 0.5cm margin
Sup border 1 cm margin
Inf border 1 cm margin
Lateral border 1cm margin
The following organs should also be outlined:
Rectum from anus taken at level of ischial tuberosities or 1cm below lower
margin of PTV to recto sigmoid (~12cm length) [aim to keep V30 <70%]
Femoral heads
Bladder
Bowel as appropriate
51
Dose Prescription
(i) Small volume throughout (prostate +/- SV’s not whole pelvis)
55 Gy intersection point dose in 20 fractions in 26 days by a 3 field technique.
(ii) With brachytherapy boost
35.75Gy intersection point dose in 13 fractions in 17 days by a 3 field technique,
followed by implant placed under general anaesthetic and the delivery of 17Gy in
2 fractions over 2 days to CTV (gammamed – Ir192)
(iii) post operative radiotherapy to prostate bed
50Gy intersection point dose in 20 fractions in 26 days by a 3 field technique
HDR monotherapy
34Gy 4# 3 days – phase two trial (with dose escalation to 38Gy) - referral to Prof Hoskin
or Dr Ostler
Neo-adjuvant hormone therapy
Currently this is indicated in the following circumstances:
1. Where brachytherapy is preferred but the gland is on initial volume study too large for
implant (suggested duration of treatment before reassessment 3 months, using LHRH
anologue)
2. In patients particularly those with a high Gleason score (> 7) or high PSA (> 15),
hormone cytoreduction for 2-3 months prior to radiotherapy is suggested, this should be
continued for at least 6 months with intermediate risk features and for 2-3years in
patients with high risk features (Gleason score>8, PSA>20). Hormonal therapy can be
with Goserelin or Bicalutamide.
Data from:
The EORTC trials used anti-androgen therapy for 3 years. Bolla et al Lancet 2002 360
103-108
The RTOG trials (RTOG 8513, 8610, 9202, 9413)used anti-androgen therapy for 4
months to indefinitely, in a series of trials. Meta-analysis Roach et al Int Journal Rad Onc
Biol Physics 47(3) 617-627.
This duration of anti-androgen treatment should be discussed with the patient and
balanced again possible side effects.
5.6.1.4 HIFU
HIFU and cryotherapy have recently become options requiring evaluation.HIFU and
cryotherapy aim respectively to eradicate prostate cancer by heating the gland using
ultrasound or by freezing it. Both technologies have been the subject of NICE
Interventional procedure Guidance on their use as primary therapy and for men with
recurrent disease (NICE 2005a, 2005b, 2005c). Although they have been assessed for
use on the basis of safety and efficacy, the guidance documents drew attention to the
lack of evidence on quality f life and long term survival.
5.6.2 PSA only recurrence after definitive treatment
Defining the site of cancer recurrence after local therapy is important in the selection of
appropriate therapeutic intervention, because patients with local recurrence only may be
52
cured by secondary localised treatment. PSA kinetics after primary local therapy has
been used to distinguish men with local recurrence from those with distant spread.



PSA elevation within 2 yr after radical prostatectomy was associated with distant
recurrence. Also, 94% of men with local recurrence had PSA velocity of <
0.75ng/mL/yr at 1 yr after prostatectomy, compared with only 46% of patients
who went on to develop metastatic disease
PSA doubling time of <1 yr was predictive of distant recurrence
Rapidly rising PSA after primary local therapy is highly suggestive of distant
metastases.
Digital rectal examination (DRE) has been shown to be unreliable in evaluation of
patients for local recurrence, since more than 50% of men with biopsy-proven local
recurrence have an unremarkable examination.
The role of transrectal ultrasound-guided (TRUS) biopsy in detection of local recurrence
is controversial. Positive anastomotic biopsy does not predict an improved outcome after
radiotherapy following radical prostatectomy.
Only preradiation PSA of ≥1 ng/mL and seminal vesicle invasion were significant
independent predictors of biochemical failure. Anastomotic biopsy may not be necessary
for detection of local recurrence in surgically treated patients.
After RP, therapeutic options include:
 PSA surveillance
 radiation therapy to the prostatic bed
 androgen deprivation
 intermittent androgen deprivation
 chemohormonal approaches – these should be within a clinical trial.
The same therapeutic options might be applied for PSA recurrences following radiation
therapy; in addition,
 salvage prostatectomy,
 cryotherapy
5.6.2.1 Radiation therapy for PSA-only recurrence
Considering the numerous studies on the use of radiation therapy for PSA-only
recurrence following RRP, there is a growing body of parameters predicting outcome
that might be helpful to stratify between observation, radiation and hormonal therapy. As
confirmed by various studies, the pre-radiation PSA appears to be of critical importance
in order to obtain optimal treatment results. ASTRO has published a consensus paper
recommending a dose of at least 64 Gy when the PSA level is < 1.5 ng/ml after RRP.
However, there is still a lack of data of prospective randomized trials and all studies
being performed lack long-term follow-up so that the impact on survival is unknown.
In patients with a high pre-radical prostatectomy PSA > 20 ng/ml, a Gleason score ≤ 7,
an extensive positive surgical margin and extensive extraprostatic tumour growth (pT3b,
pTxpN1), immediate hormonal therapy might be a better alternative. These
recommendations are corroborated by a recent study demonstrating that none of the
patients with a Gleason score 8, pT3b or pTxpN1 CaP remained disease-free following
radiation therapy for PSA-only recurrence after radical prostatectomy. Similarly, other
53
groups have reported disappointing disease-free survival rates after salvage
radiotherapy
5.6.2.2 Hormonal therapy for PSA-only recurrence
Hormonal therapy might be considered as an immediate therapeutic approach for
patients who have unfavourable prognostic factors after radical prostatectomy indicating
systemic disease, such as pre-radical prostatectomy PSA of > 20 ng/ml, pT3b, pTxN1,
and extensive positive surgical margins.
Recommendations for optimal therapeutic management of PSA-only recurrences
following RRP or radiation therapy are difficult to make since we cannot rely on
prospective randomized trials. There are only very few studies analyzing the clinical
utility of early androgen deprivation in locally advanced (M0) and metastatic CaP. If it is
true that the M0 category of patients with pTxN1 disease having undergone RRP reflects
PSA-only recurrences, then hormonal therapy would appear to be beneficial for some
patients with a high probability of occult systemic metastases. There is some evidence
that CAB has a pronounced survival benefit in patients with minimal metastatic disease
so that patients with PSA-only recurrences might have a similar improved survival with
combined androgen deprivation. Considering the speculative benefits, the side-effects of
traditional hormonal therapy, such as hot flushes, loss of libido, impotence, decreased
muscle mass and osteoporosis, must not be underestimated.
The use of antiandrogens alone might overcome these side-effects as demonstrated in
recent studies. Although gynaecomastia and breast tenderness were the most
predominant side-effects for the treatment of organ-confined and locally advanced CaP,
the incidence of hot flushes, loss of libido and impotence was significantly lower than
expected for LHRH-agonists and CAB Furthermore, the risk of objective progression of
the disease was significantly reduced in patients receiving bicalutamide, 150 mg.
Antiandrogens might represent a viable alternative to other modes of androgen
deprivation for the management of PSA-only recurrences, especially in young and
otherwise healthy men.
5.6.2.3 Guidelines for follow-up after treatment with curative intent
1. In asymptomatic patients, a disease-specific history and a serum PSA measurement
supplemented by DRE are the recommended tests for routine follow-up. These should
be performed at 3, 6 and 12 months after treatment, then every 6 months until 3 years,
and then annually.
2. After radical prostatectomy, a serum PSA level of more than 0.2 ng/mL is mostly
associated with residual or recurrent disease.
3. After radiation therapy, a rising PSA level, rather than a specific threshold value, is the
most reliable sign of persistent or recurrent disease.
4. Both a palpable nodule and a rising serum PSA level can be signs of local disease
recurrence.
5. Detection of local recurrence by TRUS and biopsy is only recommended if it will affect
the plan of treatment. In most cases, this is not necessary.
6. Metastasis may be detected by pelvic CT/MRI or bone scan. In asymptomatic
patients, these examinations may be omitted if the serum PSA level is less than 30
ng/ml but data on this subject is sparse.
7. Routine bone scans and other imaging studies are not recommended in asymptomatic
patients. If the patient has bone pain, a bone scan should be considered irrespective of
the serum PSA level.
54
5.6.3 Locally Advanced Prostate Cancer
These are patients defined by the following staging systems:
AJC/TNM classification: T3, N0, M0, any Grade.
External-beam irradiation, interstitial implantation of radioisotopes, and in selected cases
radical prostatectomy are used. The results of radical prostatectomy in T3 patients are
greatly inferior compared to results in patients with stage T2 cancer. Interstitial
implantation of radioisotopes is technically difficult in large tumours. External-beam
irradiation is the most appropriate treatment for most patients with T3 prostate cancer,
and large series support its success in achieving local disease control and disease-free
survival. Prognosis is greatly affected by whether regional lymph nodes are evaluated
and proven not to be involved. The patient’s symptoms related to cancer, age, and
coexisting medical illnesses should be taken into account before deciding on a
therapeutic plan.
Hormonal therapy should be used in conjunction with radiation. Several studies have
investigated its utility in patients with locally advanced disease. A prospective,
randomized trial was performed by the Radiation Therapy Oncology Group (RTOG)
(RTOG 85-31) in patients with T3, N0, or any T, N1, M0 disease who received prostatic
and pelvic radiation therapy and then were randomized to receive immediate adjuvant
goserelin or observation with administration of goserelin at time of relapse. In patients
assigned to receive adjuvant goserelin, the drug was started during the last week of the
radiation therapy course and was continued indefinitely or until signs of progression. The
actuarial overall 5-year survival rate for the entire population of 945 analyzable patients
was not statistically significantly different (75% on the adjuvant arm versus 71% on the
observation arm, P=.36). The authors report an improved actuarial 5-year local control
rate (85% versus 69%, P<.0001), freedom from distant metastasis (85% versus 71%,
P<.0001), and disease-free survival (62% versus 44%, P<.0001)
A similar trial was performed by the EORTC. Patients with T1, T2, N0-NX or T3, T4, N0
disease were randomized to receive either pelvic/prostate radiation, or identical radiation
and adjuvant goserelin (with cyproterone acetate for 1 month) starting with radiation and
continuing for 3 years. A recent update, with a median follow-up of 61 mo, confirmed the
sustained improvement in all endpoints with the addition of 3 yr of adjuvant HT. The 5-yr
local control in patients receiving adjuvant HT was 79% vs 97% for patients treated with
RT alone (p < 0.001). The 5-yr disease-free survival in patients receiving adjuvant HT
was 75% vs 40% for patients treated with RT alone (p < 0.001). The 5-yr overall survival
in patients receiving adjuvant HT was 78% vs 62% for patients treated with RT alone (p
< 0.001).
Additionally, the RTOG did a study on patients with bulky local disease (T2b, T2c, T3, or
T4), with or without nodal involvement below the common iliac chain: 456 men were
evaluable and were randomized to receive either radiation alone or radiation with
androgen ablation started 8 weeks before radiation and continued for 16 weeks. At 8
years, overall survival was not statistically significantly different; however, local control
(70% versus 58%) and disease-free survival (33% versus 21%) favoured the combined
arm.
55
Initial results from a randomized study of immediate hormonal treatment (orchidectomy
or luteinizing hormone-releasing hormone [LHRH] analogue) versus deferred treatment
(watchful waiting with hormonal therapy at progression) in men with locally advanced or
asymptomatic metastatic prostate cancer showed better overall survival and prostate
cancer-specific survival with the immediate treatment. The incidence of pathologic
fractures, spinal cord compression, and ureteric obstruction were also lower in the
immediate treatment arm.
Standard treatment options:




External-beam radiation. Hormonal therapy should be considered in In patients
particularly those with a high Gleason score (> 7) or high PSA (> 15), hormone
cytoreduction for 2-3 months prior to radiotherapy is suggested, this should be
continued for at least 6 months with intermediate risk features and for 2-3years in
patients with high risk features (Gleason score>8, PSA>20). Hormonal therapy
can be with LHRH agonist or non-steroidal AA. (Bolla et al Lancet 2002 ; Roach
et al Int Journal Rad Onc Biol Physics.)
Hormonal manipulations (LHRH agonist, Non-steroidal anti-androgen or
orchidectomy)
Radical prostatectomy, usually with pelvic lymphadenectomy (in highly selected
patients) should usually be offered within a clinical trial
Careful observation without further immediate treatment may be appropriate in
selected cases.
Symptomatic treatment:
Since many T3 patients have urinary symptoms, control of symptoms is an important
consideration in treatment. This may often be accomplished by radiation therapy, radical
surgery, transurethral resection of the prostate, or hormonal manipulation.
1. Radiation therapy. External-beam radiation therapy designed to decrease
exposure of normal tissues using methods such as computed tomography-based
3-D conformal treatment planning is under clinical evaluation.
2. Hormonal manipulations effectively used as initial therapy for prostate cancer:
1. Orchiectomy.
2. LH-RH analogues in daily or depot preparations (these agents may be
associated with tumor flare).
3. Nonsteroidal antiandrogen (e.g., flutamide, nilutamide, bicalutamide) or
steroidal antiandrogen (cyproterone acetate).
3. Palliative surgery (transurethral resection).
4. Interstitial implantation combined with external-beam radiation therapy is being
used in selected T3 patients.
5. Clinical trials employing alternative forms of radiation therapy.
5.6.4 Metastatic Prostate Cancer
Defined as (AJCC) TNM classifications:
T4, N0, M0, any G OR Any T, N1, M0, any G OR Any T, any N, M1, any G.
56
Treatment selection depends on age, coexisting medical illnesses, symptoms, and the
presence of distant metastases (most often bone) or regional lymph node involvement
only. The most common symptoms originate from the urinary tract or from bone
metastases. Palliation of symptoms from the urinary tract with transurethral resection or
radiation therapy and palliation of symptoms from bone metastases with radiation
therapy or hormonal therapy are an important part of the management of these patients.
Hormonal treatment is the mainstay of therapy for distant prostate cancer. Cure is rarely,
if ever, possible, but striking subjective or objective responses to treatment occur in most
patients. Initial results from a randomized study of immediate hormonal treatment
(orchidectomy or LHRH analogue) versus deferred treatment (watchful waiting with
hormonal therapy at progression) in men with locally advanced or asymptomatic
metastatic prostate cancer showed better overall survival and prostate cancer-specific
survival with the immediate treatment. The incidence of pathologic fractures, spinal cord
compression, and ureteric obstruction were also lower in the immediate treatment arm.
In some series, pre-treatment levels of prostate-specific antigen (PSA) are inversely
correlated with progression-free duration in patients with metastatic prostate cancer who
receive hormonal therapy. After hormonal therapy is instituted, reduction of PSA to
undetectable levels provides information regarding the duration of progression-free
status; however, decreases in PSA of less than 80% may not be very predictive.
5.6.4.1 Maximal androgen blockade (MAB)
The most recent meta-analysis suggest a possible 2% survival advantage at 5 years for
MAB over monotherapy which was statistically significant only in the groups not
receiving cyproterone (Lancet 2000; 355: 1491-1498)
Standard treatment options:
Hormonal manipulations effectively used as initial therapy for metastatic prostate cancer:



Surgical or medical orchidectomy eg. goserelin 3.6mg SC every 4wkly or 10.8mg
12wkly.
Flutamide 250mg tds or Bicalutamide 150mg daily as oral anti-androgens.
Cyproterone acetate 100mg tds (no longer first line therapy as may cause
hepatic dysfunction but used to cover initial exposure to Goserelin).
Also consider the following interventions to control local symptoms



Palliative radiation therapy.
Palliative surgery (transurethral resection).
Careful observation without further immediate treatment (in selected patients).
5.6.4.2 Intermittent androgen blockade
Patients wishing to consider IAB should be encouraged to enter a clinical trial if
available. Otherwise patients who are having intolerable side effects from antiandrogens or LH-RH analogues are suitable. Patients should be initiated on ADT for 69months initially and their PSA monitored. Once it has reached a level < 2 or they have
reached a nadir with three successive measures ADT can be discontinued. Three
monthly monitoring of the PSA is then recommended and when this rises significantly to
a predetermined threshold, ADT is reintroduced. A significant rise in patients reaching a
low level < 2 would be for this to rise above 4. It is less clear at what level anti-androgen
57
should be reintroduced in those who reach a nadir which is above 2 but a cut-off of
around 10 or three successive rises is recommended.
5.6.4.3 Guidelines for follow-up after hormonal treatment
1. Patients should be evaluated at 3 and 6 months after initiating treatment. Tests should
include at least serum PSA measurement, DRE and careful evaluation of symptoms in
order to assess the treatment response and the side-effects of treatments given.
2. Follow-up should be tailored for the individual patient, according to symptoms,
prognostic factors and the treatment given.
3. In patients with stage M0 disease with a good treatment response, follow-up is
scheduled every 6 months, and should include at least a disease-specific history, DRE
and serum PSA determination.
4. In patients with stage M1 disease with a good treatment response, follow-up is
scheduled for every 3-6 months. A minimal follow-up should include a disease-specific
history, DRE and serum PSA determination, frequently supplemented with haemoglobin,
serum creatinine and alkaline phosphatase measurements.
5. When disease progression occurs or if the patient does not respond to the treatment
given, the follow-up needs to be individualized.
6. Routine imaging in stable patients is not recommended.
5.6.4.4 Managing the Complications of Hormonal Therapy
Randomised trials of interventions for complications of hormonal therapy are limited to
the management of hot flushes, gynaecomastia and tiredness. Our recommendations
are therefore limited to the evidence available.
The interventions for hot flushes that have been studied are diethylstilboestrol,
cyproteroneacetate, megestrol acetate, clonidine, and oestrogen patches. Since the
severity and frequency of hot flushes can improve spontaneously over time, nonrandomised studies are of uncertain value. Interventions that have been used for hot
flushes, but have not been studied in randomised trials, include selective serotonin
reuptake inhibitors (SSRIs), sage, black cohosh and acupuncture.
Gynaecomastia is a common, troublesome complication of long-term bicalutamide
monotherapy.Randomised trials have studied the use of tamoxifen and of prophylactic
radiotherapy to the breast buds. Although tamoxifen was shown to be an effective
treatment of bicalutamide induced gynaecomastia, there is a theoretical concern that, as
an anti-oestrogen, it could have an adverse effect on prostate cancer control.
5.6.4.5 Hormone-Refractory Prostate Cancer
There is no universally accepted definition of hormone refractory disease. The disease
can be considered to be hormone refractory when androgen withdrawal therapy or
combined androgen blockade are no longer controlling the prostate specific antigen
(PSA) or the symptoms of the disease, or when there is radiological evidence of
progression. However hormone refractory disease, so defined, may still respond to
agents such as oestrogens or corticosteroids that probably work via the androgen
receptor. Even when the disease becomes hormone refractory the androgen receptor on
the cancer cells can remain active and LHRH a therapy is usually continued.
There is no known curative therapy for hormone refractory disease and so the goals of
treatment are to improve survival and quality of life and to control symptoms.
5.6.4.6 Chemotherapy
58
A randomized trial showed improved pain control in hormone-resistant patient treated
with mitoxantrone plus prednisone compared with those treated with prednisone alone.
Differences in overall survival (OS) or measured global quality of life between the 2
treatments were not statistically significant.
In randomized trials of men with hormone-refractory prostate cancer, regimens of
docetaxel given every 3 weeks have produced better OS (at 21-33 months) than
mitoxantrone.] In a randomized trial of patients with hormone-refractory prostate cancer,
2
docetaxel (75 mg/M every 3 weeks) and docetaxel (30 mg weekly for 5 out of every 6
2
weeks) were compared with mitoxantrone (12 mg/M every 3 weeks). All patients
received oral prednisone (5 mg twice per day). Patients in the docetaxel arms also
received high-dose dexamethasone pretreatment for each docetaxel administration (8
mg were given at 12 hours, 3 hours, and 1 hour prior to the 3-week regimen; 8 mg were
given at 1 hour prior to the 5 out-of-every-6 weeks' regimen). After a median follow-up of
21 months, OS was statistically significantly better in the 3-weekly docetaxel arm (50%)
than in the mitoxantrone arm (40%, hazard ratio [HR] for death = 0.76; 95% confidence
interval [CI], 0.62-0.94). The OS rate for the 5 out-of-every-6 weeks' docetaxel regimen
was 43%, which was not statistically significantly better than mitoxantrone. Quality of life
was also superior in the docetaxel arms to mitoxantrone (P = .009). In another
randomized trial of patients with hormone-refractory prostate cancer, a 3-week regimen
of estramustine (280 mg orally 3 times a day for days 1 to 5, plus daily warfarin and 325
2
mg of aspirin to prevent vascular thrombosis), and docetaxel (60 mg/M intravenously on
day 2, preceded by dexamethasone [20 mg times 3 starting the night before]) was
2
compared with mitoxantrone (12 mg/M intravenously every 3 weeks) plus prednisone (5
mg daily). After a median follow-up of 32 months, median OS was 17.5 months in the
estramustine arm versus 15.6 months in the mitoxantrone arm (P = .02; HR for death =
0.80; 95% CI, 0.67-0.97).
5.6.4.7 Oestrogens and Steroids
Diethylstilboestrol is a synthetic oestrogen that can reduce the PSA level in men with
hormone refractory disease. There is also research interest in the use of transdermal
oestrogens as an alternative to LHRHa’s in newly diagnosed prostate cancer.
Corticosteroids can be very useful in men with hormone-refractory prostate cancer. Low
dose steroids can reduce the production of adrenal androgens in men on androgen
withdrawal by suppressing adrenocorticotropic hormone (ACTH) secretion from the
pituitary. This effect can be achieved by physiological doses of corticosteroids such as
dexamethasone, prednisolone or hydrocortisone. Other mechanisms of action have also
been postulated to explain the fall in PSA that has been reported with corticosteroids.
Higher dose steroids can have an anti-inflammatory effect on bone metastases.
5.6.4.8 Imaging
The natural history of clinically occult spinal cord compression in prostate cancer is
unknown and there is little published data on the use of spinal magnetic resonance
imaging (MRI) in this clinical setting. The value of prophylactic irradiation for
asymptomatic cord compression is unclear. NICE is currently developing a clinical
guideline on metastatic spinal cord compression which may expand these
recommendations.
5.6.4.9 Bone Targeted Therapies
59
Men with prostate cancer may benefit from bone targeted therapies such as
bisphosphonates and Strontium-89, either as treatment for symptomatic bone
metastases as a preventive measure to delay or suppress the metastases or as
treatment for the osteoporosis caused by hormonal therapy. Bisphosphonates are also
used to treat cancer-related hypercalcaemia.
Androgen withdrawal therapy is a risk factor for the development of osteoporosis.
5.6.4.10 Pelvic Targeted Therapies
Management of Obstructive Uropathy
Prostate cancer may result in unilateral or bilateral obstruction of the ureters resulting in
impaired renal function.
The development of obstructive uropathy in men with hormone-refractory prostate
cancer is a frequent, potentially fatal, event.
Decompression may allow a return to baseline renal function, palliate symptoms of
uraemia and improve quality of life. It may also lead to an earlier discharge from hospital.
However it is unlikely to significantly prolong survival, with the average life expectancy of
this group of men remaining around 6–12 months.
The most common choices for decompression lie between external placement of a
nephrostomy tube under local anaesthetic or the internal insertion of a double J stent
from the bladder to the kidney under general anaesthetic. Decompression does have an
associated complication rate and long term morbidity. Medical intervention such as highdose steroids have also shown promise.
Management of Haematuria
Locally advanced prostate cancer can result in haematuria caused by bleeding from the
prostatic urethra or base of bladder. Endoscopic control of bleeding points can be
performed under general anaesthesia. Palliative radiotherapy to the bladder base and
prostate also may be effective.
Management of Bowel Obstruction
Local extension of prostate cancer into the rectum can cause luminal narrowing or
complete obstruction. The former can usually be managed by alterations to the diet, the
prescription of aperients and consideration of radiotherapy. Complete obstruction of the
lower bowel may require a defunctioning colostomy.
5.6.5 Hormone Refactory Prostate Cancer
Secondary hormonal therapy
Except in patients with non-castration testosterone levels, it remains difficult to predict
which subset of individuals is most likely to respond to secondary hormonal strategies.
Options include
 Bicalutamide is a non-steroidal antiandrogen that demonstrates a dose response;
thus, 200 mg of bicalutamide normalizes PSA more effectively than 50 mg of
bicalutamide in patients with androgen-dependent CaP.
 Megestrol acetate is a steroidal antiandrogen with progestational activity. It has
limited antitumour activity in androgen-independent CaP and should not be
routinely used for this indication. At low doses (20 mg twice daily), it is effective in
60


suppressing hot flushes in 70% of men receiving first-line hormonal ablation. At
higher doses (160-320mg/day), the antiandrogen can stimulate appetite in
patients with cancer and could have a multidimensional role in selected
symptomatic patients with advanced CaP . Approximately 10% of circulating
androgen in humans is secreted by the adrenal glands.
Ketoconazole and corticosteroid act primarily via this mechanism, resulting in a
PSA response in about 25% of patients lasting for about 4 months.
DES has been evaluated in two studies. Prophylactic anticoagulation is
recommended on patients taking DES.
5.6.6 Palliative Care for Prostate Cancer Patients
The Dying Patient
It is important to identify when men are close to death and ensure that symptom relief
and palliative care is available to all. This may require generic or specialist palliative
care.
The effective management of symptoms at the end of life, in all care settings, is
supported by the use of appropriate care pathways. The Liverpool Care Pathway for the
Dying (http://www.mcpcil.org.uk/liverpool_care_pathway) and the Gold Standards
Framework (http://www.goldstandardsframework.nhs.uk/) are models that facilitate the
quality of care at the end of life.
Recommendations
 Men with metastatic prostate cancer should be offered tailored information and
access to specialist urology and palliative care teams to address the specific
needs of men with metastatic cancer. They should have the opportunity to
discuss any significant changes in their disease status or symptoms as these
occur.
 The regular assessment of needs should be applied systematically to men with
metastatic prostate cancer.
 Palliative interventions at any stage should be integrated into coordinated care,
and any transitions between care settings should be facilitated as smoothly as
possible.
 Healthcare professionals should discuss personal preferences for palliative care
as early as possible with men with metastatic prostate cancer, their partners and
carers. Treatment/care plans should be tailored accordingly and the preferred
place of care should be identified.
 Healthcare professionals should ensure that palliative care is available when
needed and is not limited to the end of life. It should not be restricted to being
associated with hospice care.
5.6.6.1 Bone Metastases
For local pain then local radiotherapy is indicated using a single dose of 8Gy or entry
into ongoing research trials (ibandronate vs RT)
Ribs applied field only
Spine applied field prescribed to depth
61
When opposed fields are appropriate prescribed as a mid plane dose
Hemibody radiotherapy is indicated for scattered pain not readily controlled by
analgesics and adjuvant drugs giving 6Gy single dose to the upper body and 8Gy single
dose to the lower body.
Radioisotope therapy with strontium is supported by phase III trial data (Quilty et al
Radioth Oncol 1994; 31: 33-40) and national guidelines (COIN working party, Clin Oncol
1999; 11: S81-S82)
Funding is limited and cases need to be discussed with urology lead clinician (Peter
Hoskin)
For pathological fracture internal fixation should be considered. Post operative
radiotherapy (single fraction) is usually recommended where the predicted life
expectancy is > 3 months.
Bisphosphonates have a role for persistent pain despite analgesics. Pamidronate 90mg
iv 3-4wkly for 3-6 courses and then swap to oral clodronate [as per breast protocol]
NSAIDs may be useful whilst awaiting radiotherapy
5.6.7 Radiotherapy to Prevent Gynaecomastia
Radiotherapy has been shown to reduce the development of gynaecomastia, and may
be offered prior to starting Stilboestrol therapy, or in patients to be treated with
bicalutamide for prolonged periods of time. Radiotherapy will not reduce gynaecomastia
once it has developed.
Dose prescription: 10Gy in 1# in 1 day using 6-10MeV electrons usually 6-8cm circle.
5.6.7.1 Palliative External beam radiotherapy technique
Patients will be CT planned as per radical patients (conventional planning is acceptable
if felt appropriate by clinician)
(iv) Palliation
21Gy in 3 fractions in 5 days intersection point dose 3 field technique
10Gy in 1 fractions in 1 day
62
6. Pathology
6.1 Introduction
This policy is supplementary to the relevant Royal College of Pathologists Minimum
Data Set for Prostatic, Urinary Collecting Systems, Renal and Testicular Cancers
(see below).
It describes how these Data Sets and guidelines are to be interpreted within the
Cancer Network.
The Mount Vernon Cancer Network comprises 3 main Hospital Trusts – West
Hertfordshire Hospitals NHS Trust, East & North Hertfordshire NHS Trust, and Luton
& Dunstable NHS Foundation Trust.
In October 2009, specialist urological surgery (mainly comprising prostate & bladder
surgery) was centralised at the Lister Hospital in East & North Hertfordshire NHS
Trust. Diagnostic TRUS biopsies of prostate and bladder continued to be taken at all
3 Trusts, together with renal and testicular specimens. All urological cancer cases
should be reviewed either by the local multidisciplinary team (MDT) or by the
Network SMDT. Cases can be discussed at both meetings depending on the tumour
site.
Dr Samita Agarwal has been nominated as the Network Lead Pathologist, with
support from Dr Waria Mohamid. In addition, a local lead pathologist for urological
pathology should be present at each site as well. The network lead pathologist
should attend the tumour site specific group (NSSG) meetings. All the leads should
participate in a relevant EQA scheme. They should also participate in local audit
including correlation between biopsy and resection, where relevant.
6.2 Siting of the Service
The implications for pathologist of centralisation of various surgical specialities within
the network were discussed at the Network Pathology Group where the decision was
taken to retain the resulting resection specimens at the Trust hosting this service, as
opposed to re-patriating them to the Trust where the biopsy was taken.
For Urological Pathology, those specialist pathologists not primarily employed by
East & North Hertfordshire NHS Trust and wishing to continue to participate in the
provision of the service would therefore be required to do so by a combination of
travel to the site and various forms of remote access.
For radical Prostatectomies and Cystoprostatectomies, Dr Rowena Smith from
WHHT will travel to East & North Hertfordshire NHS Trust on Mondays on a
fortnightly basis where she will participate in the dissection of the surgical specimens
generated by Mr Pancharatnam.
After the sections have been cut, the slides will be sent to Dr Rowena Smith via the
Cytology Transport to Watford General Hospital and from there the slides will then be
forwarded to her at Mount Vernon Hospital. After the case is reported, Dr Smith will
send the tape with the
report back to East & North Hertfordshire NHS Trust. The typing is done by the East
& North Hertfordshire NHS Trust secretarial staff and the case is authorised by Dr
Smith on her next visit to QEII Hospital. This will involve 1PA of Consultant time for
each visit including travelling.
6.3 Governance
The legal responsibility for the specimens will reside with the Trust in which the
specimens are produced.
63
6.4 Specimen Types
(1) Prostate core biopsies
(2) Transurethral resection of prostate (TURP)
(3) Radical Prostatectomies
(4) Other open Prostatectomies
(5) Urinary bladder
(6) Urethral and ureteric biopsies
(7) Cystectomies
(8)Cystoprostatectomies
(9) Nephrectomies
(10) Orchidectomies
Clinical information required on the specimen request form
This includes the following:
1) Presenting PSA value.
2) The clinical context and the type of specimen (whether biopsy, transurethral
resection, radical prostatectomy or nodal dissection.
3) The number and site of prostatic biopsies
4) Information about prior biopsies or prior treatment which helps in the
interpretation of microscopic findings.
5) Anti-androgen therapy alters the cytology and architecture of both benign and
malignant glands and therefore alter the significance of Gleason grading.
6) The date of completion of radiotherapy is important as, even if the therapy is
effective, the tumour cancer persist for at least two years after external beam
radiation and for up to six years for brachytherapy.
6.5 Specimen Examination
Prostate core biopsies
Technical Issues:
(1) Flat embedding
This will maximise the amount of tissue for evaluation by the Pathologist because
cores can often become curved after fixation.
(2) Sectioning
Three sections are being prepared at each level at the time of sectioning. One is for
H&E stain and two are kept as unstained spares for immunohistochemistry, if
needed.
(3) Microscopic Report:
1) Each site of the core biopsy needs to be described individually to indicate the
number of cores present where prostatic ducts and acini are included or only soft
tissue stroma is present. Depending up on the individual pathologist preference,
the benign cores can be reported together. However, all the malignant cores
should be reported individually.
2) The report should include a comment regarding the presence of absence of
HGPIN or malignancy in each site of the specimen.
3) Comment on the number of involved core biopsies by carcinoma (if more than
1 core present in 1 specimen).
4) Percentage of tumour involved per core volume or measurement.
64
5) Gleason score should include 1) The predominant component and
2) The highest grade component
6) Give total Gleason score if required, enter the tertiary Gleason grading as well.
7) Comment on the presence or absence of vascular invasion or perineural space
permeation.
8) If peri-prostatic tumour extension is seen, comment on its presence.
9) If necessary, comment on the presence of seminal vesicle tissue in the cores
from the base and whether they are involved by tumour or not.
10) Comment on non-neoplastic findings which are present, for example:
(a) Stromal/glandular inflammation
(b) Acinar stroke/glandular atrophy
(c) Granulomatous prostatitis
(d) Malakoplakia
(e) Presence of granuloma
(F) Metaplasia such as mucinous squamous etc..
11) Conclusion of the report should include a total number of positive cores v/s
the total number of cores submitted. To comment on the perineural invasion if
present.
12) If applicable, comment on the immunohistochemical findings.
6.6 Immunohistochemistry
Immunohistochemistry for basal cell markers (high molecular weight cytokeratin,
CK5/6, P63 etc should be used). The absence of a demonstrable basal layer is
supportive, but not diagnostic of malignancy.
6.7 Radical Prostatectomies
The macroscopic report should include the following information:
1) Allow the specimen to fix in formalin overnight.
2) Specimen orientation should be done. If in doubt, the surgeon should be
contacted to assist with orientation.
3) The following points help with the orientation of the specimen:
(a) The bladder neck is at the base
(b) The distal urethral margin is at the apex
(c) The seminal vesicles are superior and posterior
(d) The posterior surface is flat and irregular
(e) The anterior surface is convex
(f) The versa are stumps medial to the seminal vesicles
(g) The surgeons usually orientate the specimens by putting a suture at the
site of the right apex.
(h) Paint the entire surface with different colours according to the
Department Protocol, that is, superior surface - red, anterior- orange,
base/inferior –blue
Posterior-black, right lateral – green, left lateral- violet.
4) Weigh the organ and obtain the volume of the gland.
5) Give all 3 dimensions of the specimen
65
6) Indicate the presence of the whole prostatic gland, urethra (length), seminal
vesicles, vas and lymph nodes if present.
7) The distal (apical) margin should be removed. The resulting cone shaped
piece is divided and serially sectioned like a cervical cone biopsy. All the
pieces are embedded. The base should be dealt with in a similar manner.
8) The remaining should be serially sectioned and embedded as whole mounts
in a serial manner.
9) Take serially section both seminal vesicles and embed all of them.
10) Lay out the blocks in sequence, maintaining superior/inferior,
anterior/posterior and left/right orientation.
11) If possible, comment on macroscopically visible tumour, location, size and
presence of extra-prostatic tumour extension. Also, try to comment on the
closeness of the tumour to the surgical resection margin.
12) If possible, comment on patent or constricted urethra by tumour.
13) If possible, comment on involvement of seminal vesicles by the tumour.
6.8 Microscopy
The microscopic report should include the following information:
1) Comment on the tumour size and extent
2) Give the maximum dimension of the largest tumour area
3) Indicate tumour type to include primary and secondary Gleason patterns
4) Give the combined Gleason grade (if acinar or ductal carcinoma)
5) If required, give the tertiary Gleason component
6) Indicate whether the tumour is confined to the prostate or extra-prostatic
tumour extension is present (i.e. stage T2 or > than T2 if extra-prostatic tumour
is present).
7) Comment on the extent and location of the tumour (apical, posterior, lateral,
base or anterior).
8) Comment on the presence/absence of invasion of the seminal vesicles by the
tumour
9) Comment on the presence/absence of lymph nodes by the tumour
10) Comment on the presence/absence of perineural space permeation and
vascular invasion
11) Comment on the presence/absence of high grade PIN
12) Comment on any of the relevant microscopic findings to include involvement of
the urethra.
13) Calculate the tumour surface area and volume
14) Give the tumour p TNM staging. This is according to TNM classification of
malignant tumours, (6th edition, UICC):
T2 –confined to the prostate
T2a – tumour involving one lobe
T2b – tumour involving both lobes
T3 – tumour extending through the prostatic capsule
T3a – extra-capsular extension
T3b – tumour invades seminal vesicles
T4 – tumour is fixed or invades an adjacent structure other than the seminal
vesicle (for example bladder neck, external sphincter, rectum, muscles or pelvic
wall)
A positive basal limit is recorded as PT4.
15) Comment on whether the tumour is gland confined or shows extra-prostatic
extension.
16) Comment that a copy of the specimen photograph and block mapping is
attached to the report. All the whole mount sections are arranged in a
sequential manner. The tumour is outlined in all the sections and the
photograph is taken.
66
17) Give a summary/conclusion of the report and highlight the important
(clinically/prognostically significant) positive findings in the report.
6.9 TNM Pathological staging (6th edition, UICC)
The major change in the 6th edition affects the assessment of nodes and applies to
all cancer sites. A tumour nodule in the connective tissue of the lymph drainage area
is classified as a regional lymph node metastasis if the nodule has the form and
smooth contour of a lymph node, even in the absence of histologicially proven
residual lymph node tissue.
Pt
Primary tumour
pTx
Primary tumour cannot be assessed
pTO
No evidence of primary tumour
pT1
pT1a
pT1b
pT1c
Clinically inapparent tumour not palpable or visible by imaging
Tumour incidental histological finding in 5% or less of tissue resected.
Tumour incidental histological finding in more than 5% of tissue resected.
Tumour identified by needle biopsy (e.g. because of elevated PSA).
pT2
pT2a
pT2b
pT2c
Tumour confined within prostate
Tumour involves one half of one lobe or less
Tumour involves more than half of one lobe, but not both lobes
Tumour involves both lobes
pT3
Tumour extends through the prostate capsule
pT3a Extracapsular extension (unilateral or bilateral)
pT3b Tumour invades seminal vesicle(s)
Pt4
Tumour is fixed or invades adjacent structures other than seminal vesicles:
bladder neck, external sphincter, rectum, levator muscles or pelvic wall.
Notes
1.
2.
Tumour found in one or both lobes by needle biopsy, but not palpable or
visible by imaging, is classified as T1c.
Invasion into the prostatic apex or into (but not beyond) the prostatic
capsule is not classified as T3, but as T2.
pN -
Regional lymph nodes
pNx
Regional lymph nodes cannot be assessed
pN0
No regional lymph node metastasis
pN1
Regional lymph node metastasis
pM -
Distant metastasis
pMx
Distant metastasis cannot be assessed
pM0
No distant metastasis
pM1
Distant metastasis
67
pM1a Non-regional lymph node(s)
pM1b Bone(s)
pM1c Other sites(s)
Stage grouping
Stage 1
T1a
N0
M0
G1
Stage II
T1a
T1b, c
T1,T2
N0
N0
N0
M0
M0
M0
G2, 3-4
Any G
Any G
Stage III
T3
N0
M0
Any G
Stage IV
T4
Any T
Any T
N0
M0
N1
M0
Any N M1
Any G
Any G
Any G
6.10 Urinary bladder, urethral and ureteric biopsies, cystectomies
1) Clinical information required on the specimen request form
This includes the type of specimen (biopsy, transurethral resection, partial or
complete surgical resection) and its site of origin. Information about any history of
prior urothelial tumour and treatment is helpful as it helps in the interpretation of the
microscopic findings.
2) Preparation of specimens before dissection
Adequate formalin fixation and careful handling of large specimens with papillary
tumours prior to dissection is important as these tumours are often friable, and
carry-over of tumour cells can compromise the assessment of potential invasion.
3) Urinary bladder and Urethra
Partial cystectomy specimens usually have the form of a disc and may benefit from
pinning during fixation. Radical cystectomy and cysto-prostatectomy specimen
benefit from injection of the cavity with formalin to allow distension of the bladder
and adequate fixation. After fixative has penetrated the bladder cavity, it can be
helpful to place some sutures to avoid distortion during fixation.
4) Specimen handling and block selection
All specimens are measured in three dimensions. It is useful to ink the relevant
resection margins of radial and partial resections, particularly when tumour
extends closely to them. In addition to the presence of tumour(s), white or red
areas which are generally indicative of squamous metaplasia and carcinoma in
situ should be sampled as well.
For partial cystectomy specimens, the size and appearance of the tumour
(papillary/ulcerated) and the distance of the lesion from the nearest excision
margin should be recorded. Depth of invasion and involvement of perivesical fat
should be noted, as the subdivision of the pT3 category depends on findings at
gross examination.
Radical cystectomy specimens include bladder, terminal ureters and a variable
length of urethra. In men, the prostate and seminal vesicles are also usually
received, and in women, a hysterectomy and bilateral salpingo-oophorectomy
68
specimen are generally performed as well. The specimen should be orientated by
identifying the prostate at the inferior aspect in males and the uterus posteriorly in
females. If these are absent, the tapered urethral opening is usually identifiable
and the superior/posterior aspect of the bladder is covered by the serosa of the
pelvic peritoneum.
The bladder and attached organs should be measured in three dimensions, and
circumferential resection margins inked where appropriate. The ureters should be
identified and the lengths and diameters recorded. The ureteric and urethral
resection margins, including the prostate should be sampled at this point. The
relationship between the bladder and adjacent organs (prostate, uterus) should be
recorded. The specimen can then be separated into anterior and posterior or left
and right portions cutting along a probe inserted into the urethra. Thorough
sampling of the prostate and representation of the prostatic resection margin is
useful for the detection and involvement by urothelial carcinoma and of
synchronous prostatic adenocarcinoma.
Unsuspected adenocarcinoma of the prostate is found in up to 51% of cases.
Where an incidental focus of prostatic adenocarcinoma is found, the entire
prostate is then sampled in whole mount sections using the protocols similar to
those for radical prostatectomy specimens.
Once the bladder cavity is exposed, the size, appearance (papillary,nodular or
ulcerated), site and depth of tumour infiltration of each tumour should be noted
after taking consecutive specimens perpendicular to the bladder wall. The
presence of tumour in the perivesical fat should be noted as macroscopic
identification invasion upstages the tumour to the pT3b category. The ureteric
insertion should be identified and their relationship with the tumour recorded. The
perivesical adipose tissue should be examined for lymph nodes although these
are rarely found. Pelvic lymphadenectomy specimens are generally sent
separately.
5) Block Selection
Blocks which are taken to confirm gross findings include the following:
 ureteric and urethral resection margins
 surgical resection margins for partial cystectomy specimens
 tumour (to include the maximal depth of invasion and any close surgical
/serosal resection margin)
 bladder mucosa from trigone, anterior, right and left lateral, and
posterior walls, and the dome, including any urachal remnants
 longitudinal section through ureterovesical junction, which is useful to
assess for CIS or involvement by invasive carcinoma.
 prostatic urethra, prostate and seminal vesicles or uterus, tubes and
ovaries
 any palpable lymph nodes in perivesical fat.
6) Nodal dissections
If lymph nodes are received separately, they should be measured and
described. Often processing the entire specimen is a solution.
7) Macroscopic items to be included in the report
 Appearance of the tumour (papillary or flat)
 Number of tumours
 Tumour size
 Tumour location
69


Extent of invasion (for the urinary bladder, macroscopic identification
of tumour in perivesical fat indicates a stage of pT3b (rather than
pT3a) if only identified microscopically)
Distance of the resection margin of site of positive margin
8) Microscopic items
 Tumour subtype (including variants of urothelial carcinoma and the
presence of divergent differentiation)
 Tumour grade (WHO 2004 classification)
 Tumour stage (pT classification)
 Microvascular invasion
 Margin status
 Presence and extent of associated carcinoma in-situ
 Regional nodal status, including number involved related to total
number and the presence of extracapsular spread
 Cystoprostatectomy – presence or absence of prostatic
adenocarcinoma and if so, the grade, stage and margin status
 Depth of invasion into the lamina propria, measured in mm or
recorded as a pT1a (invasion into stromal cores), pT1b (invasion into
lamina propria) or pT1c (invasion into the muscularis mucosae)
 Any significant pathology in the attached organs
9) TNM classification
The sixth edition of TNM is recommended.
6.11 Reporting of small biopsy specimens
1) Transurethral resection of bladder tumour (TURBT)
These operations are usually performed for larger papillary or solid lesions.
Specimens are weighed or measured in aggregate. There is no evidence
concerning sampling policies of large TURBTs sampled and detection of
invasion. Small resections are usually all embedded and larger specimens can
be sampled (up to 3 to 4 blocks), attempting to include larger fragments with
muscle wall. If detrusor muscle is not present in the initial sections, it is worth
considering further sampling for accurate staging. In particular, if the initial
sections show invasion into the lamina propria (pT1), complete embedding of
the remaining specimen may reveal muscle invasion, leading to clinically
important upstaging to pT2. Occasionally, levels in selected blocks will clarify
stage.
A separate biopsy may be sent from the base of the lesion (including muscle)
to assess invasion of deep tissues. Random biopsies from red areas or from
cystoscopically normal urothelium may be sent to determine whether dysplasia
or carcinoma in-situ are present.
2) Microscopy
 Tumour subtype (including variants of urothelial carcinoma and the
presence of divergent differentiation)
 Tumour grade (WHO 2004)
 Tumour stage
 Microvascular invasion
 Presence or absence of detrusor muscle
 Presence or absence of flat urothelium, comment on presence of CIS,
dysplasia or normal tissue
70
6.12 Reporting of frozen sections
Frozen sections are occasionally required for ureteric or urethral resection margins
during prostatectomies or nephroureterectomies. Frozen sections on regional lymph
nodes should not be done routinely due to problems with sampling.
6.13 TNM Pathological Staging (6th Edition, UICC)
The only difference from the 5th edition, which affects all tumour sites, affects
assessment of lymph nodes. A tumour in the connective tissue of the lymph drainage
area is classified as a regional lymph node metastasis if the nodule has the form and
smooth contour of a lymph node, even in the absence of histologically proven
residual lymph node tissue. Classification of metastasis is the same for all sites, but
primary tumour staging and stage grouping vary according to site and assessment of
lymph nodes is different for the urethra.
For all sites, in the case of multiple tumours, the tumour with the highest Tcategory
should be classified and the multiplicity or number of tumours should be indicated in
parentheses, e.g. pT2(m) or pT2 (5).
6.13.1 Renal pelvis and ureter
pT -
Primary tumour
pTX
pT0
pTa
pTis
pT1
pT2
pT3
Primary tumour cannot be assessed.
No evidence of primary tumour.
Non-invasive papillary carcinoma
Carcinoma in situ.
Tumour invades subepithelial connective tissue.
Tumour invades muscularis.
(Renal pelvis) Tumour invades beyond muscularis into peripelvic fat or
renal parenchyma.
(Ureter) Tumour invades beyond muscularis into periureteric fat.
pT4
Tumour invades adjacent organs or through the kidney into
peirnephric fat.
pN -
Regional Lymph Nodes
pNX
pN0
pN1
pN2
pN3
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Metastasis in a single lymph node 2cm or less in greates dimension.
Metastasis in a single lymph node more than 2cm but not more than
5cm in greatest dimension, or multiple lymph nodes, none more than
5cm in greatest dimension.
Metastasis in a lymph node more than 5cm in greatest dimension.
pM -
Distant Metastasis
pMX
pM0
pM1
Distant metastasis cannot be assessed.
No distant metastasis.
Distant metastasis.
Stage Grouping
71
Stage 0a
Stage 0is
Stage I
Stage II
Stage III
Stage IV
Ta
Tis
T1
T2
T3
T4
Any T
Any T
N0
N0
N0
N0
N0
N0
N1, N2, N3
Any N
M0
M0
M0
M0
M0
M0
M0
M1
6.13.2 Urinary bladder
pT - Primary Tumour
pTX
pT0
pTa
pTis
pT1
pT2
Primary tumour cannot be assessed.
No evidence of primary tumour.
Non-invasive papillary carcinoma.
Carcinoma in-situ.
Tumour invades subepithelial connective tissue
Tumour invades muscle:
pT2a Tumour invades superficial muscle (inner half);
pT2b Tumour invades deep muscle (outer half);
pT3
pT3a
pT3B
Tumour invades perivesical tissue:
microscopically;
macroscopically (extravesical mass).
pT4
Tumour invades any of the following prostate, uterus, vagina, pelvic
wall, abdominal wall;
Tumour invades prostate, uterus or vagina;
Tumour invades pelvic wall or abdominal wall.
T4a
T4b
PN -
Regional Lymph Nodes
pNX
pN0
pN1
pN2
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Metastasis in a single lymph node 2cm or less in greatest dimension
Metastasis in a single lymph node more than 2cm but not more than 5cm in
greatest dimension, or multiple lymph nodes, none more than 5cm in greatest
dimension.
pN3
Metastasis in a lymph node more than 5cm in greatest dimension.
PM - Distant Metastasis
pMX
pM0
pM1
Distant metastasis cannot be assessed.
No distant metastasis.
Distant metastasis
Stage Grouping
Stage 0a
Stage 0is
Ta
Tis
N0
N0
M0
M0
72
Stage I
Stage II
Stage III
T1
T2a,b
T3a,b
T4a
No
N0
N0
N0
M0
M0
M0
M0
Stage IV
T4b
Any T
Any T
N0
N1, N2, N3
Any N
M0
M0
M1
Urethra
pT - Primary Tumour
pTX
pT0
Primary tumour cannot be assessed.
No evidence of primary tumour.
Male and female
pTa
pTis
pT1
pT2
pT3
pT4
Non-invasive papillary, polypoid or verrucous carcinoma*
Carcinoma in-situ
Tumour invades subepithelial connective tissue.
Tumour invades any of the following: corpus spongiosum, prostate,
periurethral muscle.
Tumour invades any of the following: corpus cavernosum, beyong prostatic
capsule, anterior vagina, bladder neck.
Tumour invades other adjacent organs.
* Most verrucous carcinomas arise from penile skin rather than urethra, readers are
referred to the penile dataset for clarification.
Transitional cell carcinoma of the prostate (prostatic urethra)
pTis pu
Carcinoma in situ, involvement of prostatic urethra.
pTis pd
Carcinoma in situ, involvement of prostatic ducts.
pT1
Tumour invades subepithelial connective tissue.
pT2
Tumour invades any of the following: prostatic stroma, corpus spongiosum,
periurethral muscle.
pT4
Tumour invades other adjacent organs (invasion of bladder).
pN-
Regional Lymph Nodes
pNx
pN0
pN1
pN2
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Metastasis in a single lymph no de 2cm or less in greatest dimension.
Metastasis in a single lymph node more than 2cm or multiple lymph nodes.
pM - Distant Metastasis
pMx
pM0
Pm1
Distant metastasis cannot be assessed.
No distant metastasis.
Distant metastasis.
Stage Grouping
73
Stage 0a
Stage 0is
Stage I
Stage II
Stage III
Stage IV
Ta
Tis
Tis pu
Tis pd
T1
T2
T1, T2
T3
T4
Any T
Any T
N0
N0
N0
N0
N0
N0
N0
N0, N1
N0, N1
N2
Any N
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
6.14 Orchidectomies
1. Clinical information required on specimen request form
This includes the following:
 Laterality
 The type of specimen (biopsy, simple or radical orchidectomy,
lymphadenectomy or post-chemotherapy residual mass)
 The anatomical origin of lymph nodes
 History of prior testicular tumours and treatment.
 Information concerning serum tumour markers is useful, although results
may not always be available at the time the clinicians submit the specimen.
2. Preparation of specimens before dissection
Orchidectomy and lymphadenectomy specimens generally require fixation in
formalin for 24 hours at least. A careful incision into capsule can be useful for
tumour preservation.
3. Specimen handling and block selection
6.15 Gross examination
1. Orchidectomy specimens
Radical testicular specimens should be orientated by identifying the cord, the
slightly more bulbous head of epididymis tapering to the tail of the epididymis,
separated from the testis proper by the epididymal sinus.
Specimens are measures in three dimensions and the length of spermatic cord
recorded. The terms of proximal and distal are best avoided when referring to
the cord as they can cause confusion. A block is taken from the cord resection
margin prior to incision of the tumour to avoid contamination. Sections from the
mid point and the base of can also be taken at this time, as they more
commonly reveal vascular invasion than the cord resection margin.
Direct invasion into the cord, whether into the lower cord or the surrounding
fibro adipose tissue outside the tunica, should be noted for staging purposes
(pT3). The parietal tunica vaginalis can then be reflected and the presence of a
hydrocele and/or adhesions noted. Unless there is invasion through the tunica
albuginea into the vaginalis, the vaginalis is often not represented in tissue
sections as it separates from the testis. Breaches in the tunica are also noted.
The specimen can then be bivalved through the rete and epididymis.
The following features should be noted:
74





Tumour location (upper pole, mid section or lower pole)
The appearance (solid or cystic) and colour of the tumour
The maximum tumour size
The relationship of the tumour to the tunicas, rete (if identifiable), epididymis
and cord
The presence of abnormalities in the residual normal testis.
2. Primary lymphadenectomy specimens
Although retroperitoneal lymph node dissections can be performed as an
alternative to surveillance or chemotherapy in patients with stage I disease, this
is unusual in UK. Any such specimens are measures in three dimensions.
Lymph nodes are identified and sampled.
3. Excision of residual masses after chemotherapy
A complete retroperitoneal lymph node may be performed in these cases but
often only the involved lymph nodes are removed. Specimens are measured in
three dimensions. Surgical resection margins should be inked.
4. Block selection
Orchidectomy
Blocks are selected to represent:
 The cord resection margin, mid point and base of cord
 Relationship of the tumour to the rete tesis, epididymis and cord
 The minimum distance of the tumour to the nearest inked resection
margin for partial orchidectomies
 All areas of the tumour (s) with different macroscopic appearances
(solid, cystic, pale or haemorrhagic)
 Adjacent testis including the capsule, a common site for vascular
invasion
 Uninvolved testis.
5. Retroperitoneal lymph node resection and post-chemotherapy residual masses.
Blocks are selected to represent:
 All areas of the positive node(s)
 The minimum distance of the tumour to the nearest inked resection
margin.
 All macroscopically negative nodes to search for micrometastatic
disease.
6. Microscopic items
 Tumour subtype (s)
 Invasion of the rete testis or epididymis
 Direct invasion of the cord
 Vascular/lymphatic invasion
 Cord resection margin
 Surgical margin status
 Primary tumour category (Pt stage)
 Regional nodal status
 Presence or absence of intratubular germ cell neoplasia
 Presence of normal spermatogenesis
7. Lymphadenectomies
 Tumour subtype (s)
75


Viability of the tumour(s)
Margin status
8. TNM Classification
The 6th edition of TNM is recommended
9. Reporting of biopsy specimens
Testicular biopsies are most commonly performed in the context of infertility and
intratubular germ cell neoplasia may be an “incidental finding”.
Generally three levels are taken. It is useful to retain spare sections of
immunocytochemistry in case of doubt about diagnosis of intratubular germ cell
neoplasia.
10. Macroscopic items
Biopsies are measured and completely embedded.
11. Microscopic items
 Approximate number of tubular cross-sections present.
 Assessment of spermatogenesis
 Presence or absence of intratubular germ cell neoplasia.
12. Reporting of Frozen Sections
Frozen sections of testicular lesions are rarely required as ultrasound diagnosis
is extremely reliable. However, they may be requested to confirm the diagnosis
prior to orchidectomy in patients with bilateral tumour or if clinical findings are
equivocal. The identification of undifferentiated teratoma is usually
straightforward but the distinction between seminoma with a prominent
granulomatous reaction and a reactive process may be difficult. Similarly, the
distinction between teratoma differentiated and an epidermal cyst is
compromised by the problem of sampling as the diagnosis of teratoma
differentiated is made on the demonstration of skin appendages, nonsquamous somatic elements or intratubular germ cell neoplasia. Urologists and
their patients must be made aware of the inherent difficulties of the technique
and these potential pitfalls.
TNM Pathological staging (6th Edition, UICC)
pT
Primary tumour
PTx
Primary tumour cannot be assessed (used if no radical orchidectomy
has been performed, except for pTis and pT4, where radical
orchidectomy is not always necessary for classification purposes).
pT0
No evidence of primary tumour ( e.g histological scar in testis).
pTis
Intratubular germ cell neoplasia (carcinoma in situ)
pT1
Tumour limited to testis and epididymis without vascular/lymphatic
invasion; tumour may invade tunica albuginea but not tunica vaginalis.
pT2
Tumour limited to testis and epididymis with vascular/lymphatic
invasion, or tumour extending through tunica albuginea with
involvement of tunica vaginalis.
76
pT3
Tumour invade spermatic cord with or without vascular/lymphatic
invasion
pT4
Tumour invade scrotum with or without vascular/lymphatic invasion
In the case of multiple tumours, the tumour with the highest T category should
be classified and the multiplicity or number of tumours should be indicated in
parentheses, e.g pT2 (m) or pT2 (5).
pN
Regional lymph nodes
The regional lymph nodes are the abdominal para-aortic (periaortic), preaortic,
interaortocaval precaval, paracaval, retrocaval, and retroaortic nodes. Nodes
along the spermatic vein should be considered regional.
Laterality does not affect the N classification
The intrapelvic and the inguinal nodes are considered regional after scrotal or
inguinal surgery.
pNx
Regional lymph nodes cannot be assessed
pN0
No regional lymph node metastasis
pN1
Metastasis with a lymph node mass 2cm or less in greatest dimension
and 5 or fewer positive nodes, none more than 2cm in greatest
dimension.
pN2
Metastasis with a lymph node mass more than 2cm but not more than
5cm in greates dimension; or more than 5 nodes positive, none more
than 5cm; or evidence of extranodal extension of tumour.
pN3
Metastasis with a lymph node mass more than 5cm in greatest
dimension.
pM
Distant metastasis
pMx
Distant metastasis cannot be assessed
pM0
No distant metastasis
pM1
Distant metastasis
pM1a Non-regional lymph node (s) or lung
pM1b Other sites
S
Serum tumour markers
SX
Serum marker studies not available or not performed
S0
Serum marker study levels within normal limits
77
LDH
S1
<1.5 x N
and
S2
1.5 -10 x N
or
S3
>10 x N
or
hCG (mIU/ml)
AFP(ng/ml)
<5000
and
5000 -50,000 or
1000 -10,000
>50,000
or
<1000
>10,000
N indicates the upper limit of normal for the LDH assay.
Stage grouping
Stage 0
pTis
N0
M0
S0, SX
Stage I
pT1 – 4
N0
M0
SX
Stage I A
pT1
N0
M0
S0
Stage IB
pT2
N0
M0
S0
pT3
N0
M0
S0
pT4
N0
M0
S0
Stage IS
Any pT/TX
N0
M0
S1 -3
Stage II
Any pT/TX
N1- 3
M0
Sx
Stage IIA
Any pT/TX
N1
M0
S0
Any pT/TX
N1
M0
S1
Stage IIB
Any Pt/TX
Any pT/TX
N2
N2
M0
M0
S0
S1
Stage IIC
Any pT/TX
Any pT/TX
N3
N3
M0
M0
S0
S1
Stage III
Stage IIIA
Any pT/TX
Any pT/Tx
Any pT/TX
Any N
Any N
Any N
M1, M1a
M1, M1a
M1, M1a
SX
S0
S1
Stage IIIB
Any pT/TX
Any Pt/TX
N1-3
Any N
M0
M1, M1a
S2
S2
Stage IIIC
Any pT/TX
Any pT/Tx
Any pT/Tx
N1-3
Any N
Any N
M0
M1, M1a
M1b
S3
S3
Any S
6.16 Nephrectomies:
1. Clinical information required on the specimen request form:
78
a)
b)
c)
d)
e)
Any family of history of renal cancer
Patient has clinically confined or metastatic disease
Laterality of the specimen
Operation type (partial or radical, open or laparoscopic)
Timing of any pre-operative embolisation
2. Preparation of the specimen before resection:
The kidney is opened longitudinally to divide the kidney into broadly
symmetrical anterior and posterior halves, but taking care not to cut through
the hilum.
 Specimen handling and block selection
 Gross examination
 Weight and measurement of the specimen
 The perinephric fat should not be stripped as this hinders the
interpretation of direct invasion
 The specimen should be orientated by identifying the ureter, extending
inferiorly from the renal sinus along the medial border. At the renal
hilum, the renal vein is most anterior with the artery behind it and both
normally lie anterior to the renal pelvis.
 The presence or absence of adrenal gland – whether or not it appears
directly to be invaded by carcinoma (stage pT3a), this is different from
a blood-borne metastasis (classified as pM1 in the TNM system). If
the tumour appears to extend close to a surgical resection margin, the
surface in question should be inked.
 The renal vein requires careful inspection to identify the potential
presence of tumour.
 The presence of lymph nodes near the hilum should be noted.
 The location of the tumour, whether predominantly cortical or
medullary, the appearance and the maximum dimension of the tumour
should be recorded.
 A photographic record of the specimen is useful.
3. Block Selection
 All potential lymph nodes;
 Adrenal glands if present,
 Resection margins of ureter and renal vein
 Potential areas of invasion into the main renal vein or its tributaries
 Foci suspicious of invasion into the collecting system
 The interface between the tumour and the perinephric and renal sinus
fat
 The interface between the tumour and adjacent renal parenchyma
 Areas where the cut surface of the tumour appears pale, as this may
indicate sarcomatoid change
 An area adjacent to and including some necrosis if present
 Areas where tumour is closest to a resection margin
 Any satellite lesion, random block from normal kidney away from the
tumour.
4. Microscopic
 Tumour subtype
 Tumour grade
 Primary tumour category (pT stage);
 Histological tumour necrosis;
79



Microvascular invasion
Margin status
Regional nodal status including the number involved relative to total
number
5. Reporting of small biopsy specimens
Biopsies are not normally performed prior to nephrectomy as imaging is
generally characteristic. When there is doubt about malignancy, such as in
complex cystic lesions, sampling errors are such that biopsies may not be
helpful in the distinction between benign and malignant lesions. However,
biopsies may be useful to confirm an alternative diagnosis, especially where
surgery can be avoided. Patients with malignant lymphoma should be
referred to haematological MDT, the rare sarcoma should be dealt with by the
relevant multidisciplinary team. Finally, it is recommended that when a patient
has not undergone nephrectomy, a biopsy should be performed to confirm the
diagnosis prior to commencement of anti-cancer therapy.
As biopsy cores are generally small and it is often helpful to take only an
initial shallow section for diagnosis to maximize the amount of tissue available
for immunocytochemistry.
6. Reporting of frozen sections
Intraoperative examination of resection margins is performed in some
institutions during partial nephrectomies.
TNM PATHOLOGICAL STAGING (6TH EDITION, UICC)
pT -
Primary Tumour
pTx
pT0
pT1
Primary tumour cannot be assessed
No evidence of primary tumour
Tumour 7cm or less in greatest dimension, limited to the kidney
pT1a Tumour 4cm or less
pT1b Tumour more than 4cm but not more than 7cm
pT2
Tumour more than 7cm at greates dimension, limited to the kidney
pT3
Tumour extends into major veins or directly invades adrenal gland or
perinephric tissues but not beyond Gerota fascia.
pT3a Tumour directly invades adrenal gland or perinephric (including renal
sinus) tissues but not beyond Gerota fascia
pT3b Tumour grossly extends into renal vein(s) or vena cava or its wall
below the diaphragm
pT3c
Tumour grossly extends into vena cava or its wall above the
diagphragm.
Pt4
Tumour directly invades beyond Gerata fascia
80
In the case of multiple tumours, the tumour with the highest T category should
be classified and the multiplicity or number of tumours should be indicated in
parentheses, e.g pT2 (m) or pT2 (5).
pN - Regional Lymph Nodes
pNx
pN0
pN1
pN2
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single regional lymph node
Metastasis in more than one regional lymph node
pM -
Distant Metastasis
pMX
pM0
pM1
Distant metastasis cannot be assessed
No distant metastasis
Distant metastasis
Stage Grouping
Stage I
Stage II
Stage III
Stage IV
T1
T2
T3
T1, T2, T3
T4
Any T
Any T
N0
N0
N0
N1
N0, N1
N2
Any N
M0
M0
M0
M0
M0
M0
M1
8. Multi-disciplinary meetings
These will take place on Wednesday afternoon. Each Trust will have a local MDT
meeting for approximately one hour, in which biopsies and other local specimens will
be discussed. The local lead pathologist or a deputy will be present at these
meetings. The Trust will then link up by video conferencing for a Specialist MDT
meeting for a further hour at which specialist cases will be discussed, primarily
bladder and prostate resection. The Network lead pathologist at least will be present
for this part of the meeting and it is good practice for the local pathologists to
contribute also.
9. Audit
All pathologists reporting urological cancer specimens should participate in a relevant
EQA scheme and in local audit (including an assessment of consistency where more
than one pathologist participates in service provision). Audit may take the form of:
·
·
·
·
review of compliant with procedures for specimen examination and
reporting
completeness of datasets
systematic logging of diagnostic agreement/disagreement during review
of cases for MDTMs
correlation of tumour between biopsy and resection specimens, where
relevant.
The results of the audit process should be discussed with all pathologists who
participate in service delivery.
10. Referral for Review or Second Opinion
81
Cases are reviewed within the Network as pat of the preparation for the MDT
meetings. If a pathologist requires a second opinion on a case, this should be initially
sought within the local Trust, then within the Network. If it is necessary to refer cases
outside the Network, then the following pathologists have been reliable opinions in
the past:
Dr. Cathy Corbishley St George’s Hospital
Dr. Ashish Chandra
St. Thomas Hospital
References
1.
2.
3.
4.
5.
Sobin LH, Wittekind C. TNM Classification of Malignant Tumours (6th edition.
New York: Wiley-Liss, 2002.
Royal College of Pathologists, Minimum Dataset for Prostatic Carcinoma,
October 2009.
http://www.rcpath.org/resources/pdf/G084datasetprostaticcarcinomaoct09.pdf
Royal College of Pathologists, Minimum Dataset for Tumours of the Urinary
Collecting System, January 2007
http://www.rcpath.org/resources/pdf/G044TumoursUrinaryCollectingSystemFI
NAL.pdf
Royal College of Pathologists, Minimum Dataset for Adult Renal Parenchymal
Cancer, November 2006
http://www.rcpath.org/resources/pdf/G037FINALAdultrenaldatasetNov06.pdf
Royal College of Pathologists, Minimum Dataset for Testicular Tumours and
Post-Chemotherapy Residual Masses, October 2007
http://www.rcpath.org/resources/pdf/G046testisdatasetoct07.pdf
82
7. Rarer Cancer and Supportive Care Referral Guidelines
7.1 Clinical and Referral Guidelines
11-1A-205g; 11-1A-206g; 11-1A-207g; 11-1A208g 11-1A-209g; 11-1A-211g; 11-1A-212g; 11-1A-213g
Network clinical guidelines have been agreed and are reiewed annually by the NSSG for the
referral, diagnosis, treatment and follow up of all new and recurrent cancers of the bladder,
prostate and kidney. In addition the network has agreed Urology Pathology Guidelines.
7.2 Supranetwork Guidelines
Management of Soft Tissue Sarcomas
As defined in the NICE Improving Outcomes Guidance for the management of Sarcoma
(2008) all sarcomas are to be discussed at a designated sarcoma centre.
MVCN does not host a sarcoma centre, nor does it have a designated clinic operating in any
of the 3 acute hospital trusts. All patients must be referred to the sarcoma (supranetwork)
multidisciplinary team for discussion at the earliest suspicion of sarcoma, or when histology
identifies an unexpected sarcoma.
The MVCN designated centre is the London and South East Sarcoma Network, which is
hosted by the Royal National Orthapedic Hospital, for bone sarcomas and UCLH for soft
tissue sarcomas.
The UCLH MDT is held on Fridays at 08:00, and is a joint MDT, videoconferenced with the
RNOH Bone and soft tissue sarcoma MDT.
The contact details are:
MDT Co-ordinator
Maria Jose
[email protected]
Telephone - 0207 691 2303 ext 4821
Fax - 020 3447 9536
UCLH Sarcoma MDT Lead Clinician
Dr Jeremy Whelan
[email protected]
0207 380 9346
Please note: cut off for referrals is the Wednesday preceding the Friday meeting.
Children & Young Persons
Children with urological cancer (up to 16 years) must be referred to one of the two network
agreed primary treatment centres (PTC) either GOSH or Addenbrookes. Young persons
with urological malignancies (16-24) will be referred to the network agreed Young Persons
MDT at UCLH for discussion. Place of treatment for this group will depend upon their age.
16/17/18 year olds will be treated at the PTC, but 19-24 year olds have the choice between
being treated at the PTC or locally. This local treatment will follow the treatment plan
agreed at the PTC MDT.
7.3 Generic Guidance
Acute Oncology Services
National Chemotherapy Advisory Group, guided partly by reports from NCEPOD and NPSA
and from previous cancer peer review results, has recommended that a more systematic
approach should be taken to dealing with cancer-related emergencies. These
recommendations have been embodied in the concept of the ‘Acute Oncology Service’.
Work is now underway within the acute trusts within the Mount Vernon Cancer Network
Locality to develop a strategic approach to managing acute oncological emergencies which
reflects both local trust practice and a consistent network wide approach.
In line with this a number of policies and protocols have been developed / revised to
manage acute oncological emergencies as they present at A&E / AAU / MAU.
These have been developed by the MVCC in collaboration with the trusts and have been
agreed by the Network Acute Oncology Group.
From referral into the system the patients will be triaged to appropriate oncological input
earlier within the patient pathway. The AOS will ensure 24hr access for acute medical take
and A&E doctors to oncological assessment.
Oncological emergencies include the suspicion and diagnosis of spinal cord compression
and in these cases referral in tot the service or presentation at A&E will result in MRI, and
case discussion between MVCC and the designated spinal surgery centre to ensure earlier
detection and management of this condition.
Rehabilitation
Rehabilitation is a key component of the patient pathway. The rehabilitation specialist
services consist of:
o
o
o
o
o
Dietetics
Lymphoedema
Occupational Therapy
Physiotherapy
Speech and Language Therapy
The input from these professionals will vary depending on the patient’s diagnosis and
treatment. Attached is the Rehabilitation Pathway identifying Key Referral Triggers for
each profession.
The Mount Vernon Cancer Network Rehabilitation Services Directory is available through
the MVCN website which identifies service availability across the network.
84
Appendix 1
Mount Vernon
Cancer Network
The Supra-Network MDT for Penile
Cancer based at UCLH
GUIDELINES FOR REFERRAL,
INVESTIGATION AND MANAGEMENT of
CANCER OF THE PENIS
The Mount Vernon Cancer Network Urology TSSG agreed to adopt the North
London Supranetwork Penile Cancer Guidelines on 2nd December 2009.
To be reviewed by the Mount Vernon Cancer Network Urology TSSG as and
when they are revised and updated by the Supranetwork team.
Introduction
Incidence
Carcinoma of the penis is rare, accounting for 0.4-0.6% of male malignancies, and with an
incidence of 1 in 100,000 and around 300 new cases/year in England and Wales1.
The rarity of penile cancers means there are very few prospective clinical trials investigating
the management of such tumours. Retrospective patient series provide important data on
which to base management guidelines.
Histology
The majority of invasive cancers of the penis are squamous cell carcinomas. A substantial
minority of penile cancers are of the verrucous subtype. The verrucous subtype has a better
prognosis and may be suitable for a more conservative management policy2, 3. Rarer
histology includes basal cell carcinoma, melanoma and neuroendocrine cancer4-11: such
tumours should be managed along guidelines described for those cutaneous tumours in
other sites, with modifications accounting for location.
Aetiology
Human Papilloma virus (HPV) has a strong association with both invasive squamous
carcinoma of the penis and with carcinoma-in-situ. Certain serotypes (notably HPV 16)
seem to exert transforming oncogenic potential12-16. Research is ongoing and one
subsidiary function for the supra-regional MDT is to support such work, where possible.
Cancer of the penis is uncommon amongst populations where male circumcision is
routinely practiced. This is believed to be related to the carcinogenic properties of smegma.
Skin diseases that are associated with cancer of the penis include Lichen Planus17, Lichen
Sclerosus otherwise known as Balanitis xerotica obliterans et atrophicus18, 19, and the premalignant conditions Bowen’s Disease and Erythroplasia of Queyrat (collectively termed
Carcinoma-in-Situ or CIS).
Staging
Two systems are in common usage for staging purposes: the TNM staging system (that will
be used by the MDT) and Jackson’s Stage, an older classification used in many reports.
Jackson’s Staging
Stage I
Tumor confined to glans or prepuce
Stage II
Invasion into shaft or corpora; no nodal or distant metastases
Stage III
Tumor confined to penis; operable inguinal nodal metastases
Stage IV
Tumor involves adjacent structures; inoperable inguinal nodes and/or distant
metastatic disease
TNM Staging system for penile cancer
Primary tumour
Tx Primary tumour cannot be assessed
To No evidence of primary tumour
Tis Carcinoma in situ
Ta
Non invasive verrucous type carcinoma
86
T1
Tumour invades sub-epithelial connective tissue
T2
Tumour invades corpus cavernosum and spongiosum
T3
Tumour invades urethra or prostate
T4
Tumour invades other adjacent structures
Regional lymph nodes
NX Regional lymph nodes cannot be assessed
NO No regional lymph node metastasis
N1 Metastasis in a single superficial inguinal node
N2 Metastasis in multiple or bilateral single superficial inguinal nodes
N3 Metastasis in deep inguinal or pelvic node(s), unilateral or bilateral
Distant metastasis
M0 No distant metastasis
M1 Distant metastasis
Prognostic Factors
Histology
Several studies have demonstrated a better outcome for verrucous histology compared to
squamous differentiation, with lower rates of lymph node metastases, distant metastases
and greater median survival2, 3, 20.
Reports vary over the prognostic significance of grade. It fails to emerge as an independent
prognostic factor, but poorer differentiation does predict for lymph node involvement (see
below)3, 21-23.
Vascular invasion has been reported as having prognostic significance, but this probably
relates to its influence on lymph node disease23.
T Stage
Both T stage and size are prognostic factors for lymph node involvement23, but do not
remain as independent factors when N stage is taken into account21. Similarly, depth of
invasion has been described as a prognostic indicator, but this has not been separated from
its influence on nodal metastases24.
N Stage
Locoregional lymph node status is regarded as the single most significant prognostic factor
for invasive squamous carcinoma25, 26. Univariate analyses overwhelmingly confirm the
negative impact of lymph node disease and, unusually, it remains significant in multivariate
analyses. Many factors which lose their significance in multivariate analyses do so because
they influence the likelihood of lymph node disease23, 27.
Molecular Markers
HPV positivity does not seem to confer adverse prognosis, in spite of its pathogenic role12.
Immunoreactivity for p53 is an independent predictor of poor prognosis in multivariate
analysis28.
87
Management Overview
Carcinoma-in-situ may be treated with topical agents (typically 5FU), by laser therapy, or by
local excision (including Mohs micrographic surgery).
Stage I/pT1No tumours are suitable for conservative treatment with wide local excision.
Laser therapy may be suitable for some tumours.
Tumours involving the corpora are usually treated by partial penectomy. Radiation therapy is
an acceptable alternative for selected patients, although not routine treatment in this supranetwork.
Locally advanced disease requires radical treatment, usually total or partial penectomy
and/or reconstructive surgery and thus a dedicated plastic surgeon forms part of the core
MDT.
The management of clinically involved lymph nodes involves lymphadenectomy where
possible. The investigation and management of clinically uninvolved lymph nodes may
involve sentinel lymph node biopsy (the technique referred to as “dynamic sentinel lymph
node biopsy” in some reports).
Distant metastatic disease is incurable. Patients may benefit from palliative chemotherapy.
The most active agents studied are methotrexate and cisplatin.
Verrucous Carcinoma of the Penis is a distinct clinical entity with a favourable prognosis. It
is suitable for conservative therapy including cryotherapy, laser therapy, interferon and local
excision.
Management of all patients within the SN MDT are discussed in the forum of the MDT.
REFERRAL
Sources of Referral
Currently all referrals to the Supranetwork MDT occur via local network MDTs. The majority
of referrals are from urologists, but other clinicians to whom patients with cancers of the
penis may present include dermatologists, genitourinary physicians, plastic surgeons and
general surgeons. Guidelines for referral have been distributed to all these specialties
throughout the networks contributing to the Supranetwork MDT.
The cancer services manual requires a named member of each contributing network to be
designated as a core member of the Supranetwork MDT.
The liaising member of the NE London Cancer Network to the Supranetwork MDT will
be Mr G Moir (Plastic Surgery).
*Liaising member of Surrey, West Sussex and Hampshire will be Mr R Nigam
(Urology)
 The liaising member of North London Cancer Network will be Mr S Minhas (Urology)
 The liaising member of the West London Cancer Network to the Supranetwork MDT
will be Mr M Dineen (Urology).
88
The liaising member of the Mount Vernon Network to the Supranetwork MDT will be
Mr T McNicholas (Urology).
 * The liaising member of the Thames Valley Cancer Network to the Supranetwork
MDT will be Mr P Malone (Urology).
*Currently designated Satellite centres (see operations policy)
Referral Procedure
Most patients will have undergone biopsy at a local/network level, although not all patients
are required to have this performed if there is a clinical suspicion of cancer. Referral to the
Supranetwork Team (SNT) is made via a standard pro-forma that is available to all referring
MDTs (see appendix). The referral form will be provided in both hard copy and electronic
formats. Referral by fax or email is encouraged to the SNT contact who is currently Mr Dele
Oyebo. Other referrals are co-ordinated via the PA of the SN MDT chair in order to expedite
review. Minimum data required for referral are as follows:





Demographics: Name, Date of Birth, Address, Contact Telephone number
Hospital Number (for referring hospital)
Name and contact of referring clinician and GP
Histology (if biopsy has been performed)
Imaging (if any)
The histology and imaging if performed locally is sent to the SNT prior to discussion at the
MDT meeting.
 Patients with suspected penile cancer may be referred directly to the SNT prior to
biopsy
 Initial biopsy of the lesion may be undertaken at local level before referral
 All patients with histologically-proven penile cancers must be reviewed at the SNT
THE SUPRANETWORK PENILE MDT
Core Members
Consultant Urologists
Consultant Pathologist
Consultant Radiologist
Consultant Medical Oncologist
Clinical Nurse Specialist
MDT Co-ordinator
Mr Suks Minhas (Chair), Mr Asif Muneer* (NLCN), Mr
Peter Malone (TVCN), Mr Raj Nigam (SWSHCN)
Dr A Freeman (UCLH)
Dr C Allen (UCLH)
Dr S Harland (UCLH)
Miss Clare Akers** (UCLH)
Mr Dele Oyebo (UCLH)
*core member nominated as responsible for the recruitment into clinical trials
** core member responsible for users’ issues and patient information
Extended Team Members
Consultant Urologists
Mr D Ralph (UCLH), Mr A Christopher (UCLH)
Mr M Dineen (WLCN)
89
Consultant Plastic Surgeons
Consultant Clinical Oncologist
Consultant Radiologists
Consultant Histopathologist
Clinical Nurse Practitioner
Palliative Care
Nuclear Medicine
Social Worker
Psychosexual Counsellor
Oncology Counsellors
Macmillan Cancer Information
Mr S Withey (UCLH), Mr A Mosahebi (UCLH/Royal
Free)
Dr H Payne (UCLH)
Dr Alex Kirkham (UCLH), Dr Miles Walkden (UCLH)
Dr Rupali Arora (UCLH)
Ms Fiona Holden (UCLH)
Caroline Stirling (Camden PCT), Sue Hutton (Camden
PCT)
Dr Jamshed Bomanji (UCLH)
Marianne Kilcoyne (UCLH)
Dr Mike Perring
Mary Burgess (UCLH)
Caroline Teehan (UCLH)
Meeting Arrangements
The SNT currently meets every week. The venue will be University College Hospital, in the
Theatre Seminar room (3rd Floor) where video-conferencing is available.
Corresponding members of all contributing networks are notified the week prior to the
meeting, with a list of patients to be discussed being circulated by email. Attendance is
recorded at each meeting.
Recording of Treatment Plans
Agreed recommendations from the Supranetwork Penile MDT meetings are recorded by the
MDT Co-ordinator on an agreed proforma and checked by Consultant/CNS. MDT proformas
are accessed electronically by all core team members on the shared drive and the CDR
system. Copies of the proformas are also filed in the patient’s case notes.
The record includes:








The identity of patients discussed
The diagnosis, at the time of making the referral decision
Referring clinician, hospital and network
Presentation
Previous treatments (if applicable)
Diagnostic results
Relevant clinical details including co-morbidities
Management Plan, including reasonable therapeutic options
Emergency discussions between MDT meetings should be documented in the patient’s
notes and communicated to the MDT coordinator. The decisions are made by all relevant
clinicians and the discussion takes place via phone call or personal contact where possible.
The treatment plans are then discussed in retrospect at the following MDT meeting and the
treatment decision is verified and then documented.
Discussion of Treatment Options
All patients diagnosed with penile cancer will be reviewed by a core surgical team member
of the Supranetwork MDT and specialist nurse, with access to a joint meeting with an
Oncologist. The patient’s diagnosis, MDT recommendations and treatment options will be
discussed with the patient. The patient will be given named Key Worker contact details for
the specialist nurse, and relevant patient information.
Patient Information
The MDT will provide written material for patients diagnosed with penile cancer including
information specific to the local/specialist MDT team and the provision of services offering
90
treatment at the Supranetwork centre. Written information will also be provided regarding
patients’ self-help groups, services offering psychological, social and spiritual/cultural
support and information specific to penile cancer about the disease and its treatment
options.
Communication with Patients, GPs and Referring Clinicians
All patients will be offered the opportunity of a permanent record or summary of a
consultation at which their treatment options of their diagnosis were discussed. They can
choose to decline. It is standard practice to copy all clinical correspondence to patients, GPs
and referring clinicians. MDT proformas will be faxed to GPs and referring clinicians
following each Supranetwork MDT meeting.
All patients have access to the members of the MDT to discuss problems or concerns
regarding diagnosis, treatment or any other matter. This access is principally via their Key
Worker contact. The Key Worker ensures that the patients / carers have their details.
Surgery at Host Site
All surgeries including penile reconstructive surgery and lymphadenectomy is now
performed at University College Hospital. In this context all patients referred to Thames
Valley and SWISH Networks will be seen directly at University College Hospital and their
surgeries then arranged at University College Hospital.
The only surgery performed locally will be diagnostic penile biopsies. This has been agreed
by the Network Leads for penile cancer as of 1 April.
STAGING INVESTIGATIONS
Examination
Physical Examination should include a record of the site and size of the primary tumour, the
presence of satellite lesions and the presence or absence of palpable inguinal
lymphadenopathy.
Biopsy
Biopsy of the primary lesion may be performed locally or at an agreed site after discussion
at the SNT.
Imaging
A staging CT to include the chest abdomen and pelvis is required for all newly diagnosed
patients. The imaging modality of choice for staging of the primary lesion and loco-regional
nodes will be MRI for this Supranetwork Team29, 30. MRI of the penis following intracavernosal injection of prostaglandin E1 can be arranged via the SNT.
Staging of Loco-regional Lymph Nodes
Sentinel Lymph Node Biopsy (also known as “dynamic sentinel lymph node biopsy,
SLNB) is an appropriate staging procedure for patients with intermediate and high-risk
tumours as defined by the EUA guidelines31. This would include:
 All G3 tumours,
 G2 tumours that are T1 or greater
 G1 tumours that are T2 or greater
91
SNLB has commenced at UCLH as part of a national audit coordinated by the Royal College
of Surgeons to validate the technique. Once performed for diagnostic purposes this can be
performed at the time of the penile surgery.
Palpable lymphadenopathy is was traditionally treated after 6 weeks of treatment with
broad-spectrum antibiotics, although this has recently been questioned32. Acceptable
investigations thereafter are Fine Needle Aspiration or intraoperative frozen section biopsy
immediately prior to planned radical lymphadenectomy.
MANAGEMENT GUIDELINES
Carcinoma-in-Situ
Laser Therapy
Windahl and Anderson reported recurrence in 3 of 21 patients (14%) with pTis treated with
neodymium YAG laser, 2 recurring with pTis and one with pT1 disease33. Van Benzooijen
et al reported recurrence in 5 of 19 patients (26%) again only 1 having pT1 disease34. Laser
therapy with rigorous follow-up is an acceptable treatment for CIS with excellent cosmetic
and functional results.
Topical Agents
5-fluoruracil (5FU) has been employed in the treatment of penile CIS for nearly 30 years35.
Concerns exist with regard to its lack of penetration and its limited efficacy.
Imiquimod is a topical immune stimulant. Its efficacy in the treatment of viral genital warts
led to its successful use in Penile Intraepithelial Neoplasia and Carcinoma-in-situ36-38.
The combination of 5FU and imiquimod has been employed in the management of
cutaneous (including perianal) CIS in immunosuppressed individuals39, 40. Response rates
were high and relapse rates low.
There are no randomised studies on which to base guidelines for the topical management of
CIS of the penis, but imiquimod alone or in combination would seem to be the agent of
choice at present.
Surgery
Mohs micrographic surgery has been the most successful surgical technique. It allows
confirmed clear resection margins and reported relapse rates are low41. There may be
concerns regarding cosmetic results. This technique is not currently offered at UCLH.
Systemic therapy
Interferon- administered subcutaneously has activity in PIN and verrucous penile
cancer42, 43. It is not in routine use for CIS.
Combined modality
A large trial on the use of combined modalities in the treatment of PIN demonstrated
superiority of laser ablation plus topical 5FU plus systemic interferon, with complete
remission in 96% of patients44.
 Guidance on the management of CIS will be made on a case-by-case basis. Clinical
trials are needed and entry into trial protocols will be encouraged (where available).
92
Verrucous Carcinoma of the Penis
Introduction
Verrucous carcinoma (also known by the eponym “Buschke-Lowenstein tumour”) is a less
common, well-differentiated subtype of penile cancer. HPV infection is found less frequently
than in CIS or invasive squamous carcinomas15, 45 and p53 mutation is not a feature46. It
has a low rate of lymph node invasion and, consequently, an excellent prognosis.
Occasional tumours will contain micro-foci of invasive squamous carcinoma20 and an
invasive variant associated with HPV type 11 has been described47, but these are
extremely uncommon. Conservative approaches to management are therefore indicated.
Treatment Options
 Wide Local Excision
 Cryosurgery - Debulking of tumour followed by liquid nitrogen cautery has been
described since the 1970s48. It may be combined with topical 5FU application49.
 Interferon- - intralesional and combined with local excision42, 43, 50
 Methotrexate-based chemotherapy 51
Treatment options should be discussed with the patient and in the SNT.
 Sentinel node biopsy is not indicated.
Early Invasive Squamous Carcinoma of the Penis
This encompasses Ta, T1 and T2 tumours without lymph node involvement.
General Considerations
Early invasive cancer may be upstaged either on imaging or on sentinel lymph node biopsy
(indicated for pTa tumours that are G3, pT1 tumours that are G2 or above and all pT2
tumours).
All treatment options may involve cosmetic changes, psychological morbidity and loss of
sexual function52.

All patients must be counselled by a dedicated Clinical Nurse Specialist before
treatment.
Surgical Options
Erectile function and cosmesis can be maintained using organ-sparing techniques, without
subjecting individuals to more extensive surgery. It has been suggested that welldifferentiated lesions less than 40mm in diameter may be suitable for organ conservation53.
A surgical margin of 10mm has been recommended as sufficient for G1 and G2 lesions,
while 15mm is recommended for G3 lesions54.



Tumours confined to the prepuce may be treated by circumcision alone.
Lesions confined to the glans may be treated by glans excision and split thickness
skin grafting.
Tumours invading the corpus cavernosum or corpus spongiosum (T2) must be
treated by partial penectomy combined with penile reconstruction using split
thickness skin grafting. Tumours that are more proximal may require total
penectomy.
93
Laser therapy
Laser ablation provides excellent cosmetic results. There are no randomised trials
comparing laser therapy with conservative surgery, but authors several series claim
recurrence rates equivalent to those of conservative surgery55. The overall relapse rate is
of the order of 20% and the ideal treatment strategy probably incorporates CO2 laser
ablation of the tumour followed by Nd:YAG laser coagulation to the tumour bed33.
 Laser therapy should be reserved for tumours less than 3cm in diameter and G1 or
G2 histology.
Radiotherapy
Radiotherapy is an alternative to conservation surgery, with iridium-192 wire brachytherapy
probably superior to external beam irradiation in terms of outcome and complications56-58.
Overall survival for first-line RT and salvage surgery where indicated is comparable to firstline surgery, but local control is inferior in non-randomised series59. Morbidity includes
urethral stenosis.
 It is not the policy of this Supranetwork MDT to offer radiation therapy as primary
therapy for penile tumours.
Chemotherapy
The exact role of neoadjuvant and/or adjuvant chemotherapy remains to be determined.
High response rates in small series have been claimed for neoadjuvant Cisplatin/5FU60and
this is the recommendation of the EAU54. The combination of Vincristine, Bleomycin and
Methotrexate has been used in both the adjuvant and neoadjuvant setting with favourable
reports in unrandomised series61. Trials of chemotherapy in both circumstances are
required.
 Neoadjuvant chemotherapy is an option for all patients undergoing conservative local
therapy for early disease, although this is based on limited evidence.
 The Supranetwork team will support trials of adjuvant and neoadjuvant therapy.
There is now a TPF chemotherapy trial commencing for patients with measurable residual
disease.
Locally Advanced Squamous Carcinoma of the Penis
This comprises pT3 and pT4 primary lesions or any pT with operable lymph node
involvement (clinically or microscopically as detected on sentinel lymph node biopsy).
Surgical Management of the Primary Tumour
Extirpation of the primary tumour may require partial penectomy, total penectomy and
anything up to hemi-pelvectomy for T4 lesions. The practice of demanding a clear margin of
2cm (which may be the difference between suitability for partial penectomy and the
necessity of total penectomy) has been questioned. The EAU guidelines stress only the
need for clear margins31 and there is evidence that margins of less than 10mm may suffice
for G1 and G2 tumours and 15mm for G3 lesions54.
Tumours may be downstaged by neoadjuvant chemotherapy (see below).
All patients who have undergone penile amputation should be offered reconstructive penile
surgery using a radial artery forearm free flap
Surgical Management of Loco-regional Lymph Nodes
94
Lymph node dissection is indicated for patients with proven clinical node involvement and
for patients with a positive sentinel lymph node biopsy. The operations under consideration
are:
 Sentinel Lymph Node Biopsy
 Modified Inguinal Lymph Node Dissection
 Radical Inguinal Lymph Node Dissection
 Pelvic Lymph Node Dissection
SENTINEL LYMPH NODE BIOPSY
It is important to emphasise that the term “Sentinel Lymph Node Biopsy” as used in this
document refers to the technique of lymphatic mapping and sentinel lymphadenectomy
described by Morton in 199062 and now used extensively in the staging of malignant
melanoma and breast cancer. The technique of localising sentinel node(s) by infiltrating
around the primary with vital blue dye and technetium-99m radiocolloid is distinct to the
concept of “blind” excision of the likely sentinel node (superomedial to the sapheno-femoral
junction) as popularised by Cabanas63. The term “Dynamic Sentinel Lymph Node Biopsy” is
often used in the literature on penile malignancy to differentiate the current technique from
the older practice.
The indications for SLNB are given under “Staging Investigations,” above.
Horenblas’s group has reported extensively on this procedure, and has recorded a falsenegative rate of 18%32, 64-67. They identified a number of sources of error, however,
including inadequate histological examination. They also employed the technique where
unilateral clinical node involvement was obvious, and this may have altered the results,
 Sentinel Lymph Node Biopsy may be offered to all patients at high risk of nodal
metastases, who are clinically node negative. All sentinel nodes will be examined
using the same protocol employed for melanoma sentinel nodes.
MODIFIED INGUINAL LYMPH NODE DISSECTION
The EAU guidance recommends prophylactic bilateral superficial modified inguinal lymph
node dissection for patients who are at high risk of having micro-metastasis or metastatic
spread31:
 pT1 G2 lesions with vascular invasion or nodular/vertical growth pattern

pT1 G3 lesions

Any pT2 lesion

Peri-operative frozen section must be performed of all lymph nodes sampled.
Those patients with positive nodes on frozen section must undergo immediate
radical inguinal lymph node dissection.
RADICAL INGUINAL LYMPH NODE DISSECTION
 Unilateral radical inguinal lymph node dissection is performed where positive
unilateral inguinal nodes are identified either by Sentinel Lymph Nodes Biopsy or by
frozen section during Modified Inguinal Lymph Node Dissection.
 A superficial modified inguinal lymph node dissection with frozen section is
recommended on the contra-lateral side.
 If peri-operative frozen section of nodes is positive then a contra-lateral radical
inguinal lymph node dissection must be performed.
95
PELVIC LYMPH NODE DISSECTION
The risk of pelvic nodal involvement is approximately 30% if two or more inguinal nodes are
involved26, 68, 69. Patients who have a single nodal metastasis may be offered a pelvic
lymph node dissection., subject to discussion in the Supranetwork MDT. This is offered as
either an open or laparoscopic procedure.
 Patients with 2 or more positive inguinal nodes should be advised to undergo pelvic
lymph node dissection if medically fit.
Chemotherapy
Patients with T3 lesions, or N1 or N2 disease, are eligible for neoadjuvant chemotherapy
(Cisplatin plus Irinotecan) as part of EORTC 30992. This trial is being run in London by the
Dept of Medical Oncology, Bart’s Hospital (NELCN).
Patients with T4 or N3 lesions are eligible for the same trial, with the option of extended use
of chemotherapy as the primary treatment modality.
Patients undergoing surgery without neoadjuvant chemotherapy should probably be offered
adjuvant treatment, although the regimen, duration and absolute benefit have not been
defined in any large clinical trial.
 Neoadjuvant chemotherapy should be offered to patients with locally advanced
disease.
 The Supranetwork team will actively support chemotherapy trials in this patient
group.
Metastatic Squamous Carcinoma of the Penis
Chemotherapy
Combination chemotherapy is the standard of care for patients with symptomatic metastatic
disease. This is based on subjective improvements in quality of life that attend objective
response. There is no good evidence of survival benefit for palliative chemotherapy,
although studies are few.
Drugs with the highest response rates are Methotrexate and Cisplatin in a variety of
combinations60, 70.
 Patients with metastatic disease will be offered chemotherapy as part of EORTC
30992 (Cisplatin + Irinotecan) where eligible.
 other combinations of chemotherapy will be offered as appropriate, recruiting to
clinical trials where possible
Radiotherapy
External Beam Radiotherapy has a role in palliation of distant metastatic disease and for
loco-regional control in the presence of distant metastases.
 Radiotherapy will be co-ordinated through Dr H Payne, Consultant Clinical
Oncologist, University College Hospital
Surgery
Limited surgery may have a role in the management of loco-regional disease in the
presence of distant metastases.
Reports are lacking on the use of metastatectomy as a therapeutic option for isolated distant
metastases.
Palliative Care
The Supranetwork MDT appreciates the importance of palliative care input, both in the
community and as an inpatient. Palliative care arrangements will involve GPs, community
(eg MacMillan) home care teams, social workers, district nurses and palliative care
96
physicians. These will be co-ordinated by the Clinical Nurse Specialist(s) for the
Supranetwork team.
PROTOCOL FOR PATIENT FOLLOW-UP
The schedule for follow-up recommended by the EAU31 is as follows:
Years 1 & 2
Year 3
Years 4 & 5
conservative
local
therapy
management
partial/total
2 monthly
3 monthly
6 monthly
3 monthly
6 monthly
6 monthly
penectomy
lymph node
surveillance
3 monthly
4 monthly
6 monthly
management
pNo
3 monthly
6 monthly
6 monthly
pN+
3 monthly
4 monthly
6 monthly
Physical examination is required at each visit. The value of routine imaging (ie in the
absence of symptoms) has not been established.
Follow up of patients following diagnosis and treatment of penile cancer should take place in
the clinics of core members of the Supranetwork MDT, which includes clinics at Satellite
centres (Royal Berkshire, Royal Surrey) to reduce burden of travel for patients from these
catchment areas. All histology is presented at the MDT following surgical intervention, where
further treatment or clinical/radiological follow up is planned in line with these guidelines.
AUDIT & PEER REVIEW
Audit of all cases will take place at least annually. One core member of each referring
network will be required to review cases with at least one core member of the supranetwork
team. This will ideally take place before peer review.
DATA COLLECTION
The Supranetwork MDT, in agreement with the host NSSG, will collect the Network agreed
Minimum Data Set (MDS) for Urology. The minimum dataset includes cancer waiting time
monitoring fields and the BAUS cancer registry. UCLH also in agreement to collect the
Thames Cancer Registry information.
EDUCATION & TRAINING
Core members of the team who have direct clinical contact with patients should attend the
National Advanced Communications Skills training course.
REFERENCES
1. Anon. Mortality statistics - cause, England and Wales, 1999. London: Office for National
Statistics, 2000.
2. Seixas A, Ornellas A, Marota A, Wisnescky A, Campos F, de Moraes J. Verrucous
carcinoma of the penis: retrospective analysis of 32 cases. J Urol 1994; 152:1476-1478.
3. Soria J, Fizazi K, Piron D, et al. Squamous cell carcinoma of the penis: multivariate
analysis of prognostic factors and natural history in monocentric study with a conservative
policy. Ann Oncol 1997; 8:1089-1098.
97
4. Wood E, Gardner WJ, Brown F. Spindle cell squamous carcinoma of the penis. J Urol
1972; 107:990-991.
5. Manglani K, Manaligod J, Ray B. Spindle cell carcinoma of the glans penis: a light and
electron microscopic study. Cancer 1980; 46:226-2272.
6. Oppenheim A. Sebaceous carcinoma of the penis. Arch Derm 1981; 117:306-307.
7. Bundrick W, Culkin D, Mata J, Gonzalez E, Zitman R, Venable D. Penile malignant
melanoma in association with squamous cell carcinoma of the penis. J Urol 1991; 146:13641365.
8. Kim E, Kroft S, Dalton D. Basal cell carcinoma of the penis: case report and review of the
literature. J Urol 1994; 152:1557-1550.
9. Tomic S, Warner T, Messing E, Wilding G. Penile Merkel cell carcinoma. Urology 1995;
45:1062-1065.
10. Cubilla A, Ayala M, Barreto J, Bellasai J, Noel J. Surface adenosquamous carcinoma of
the penis. A report of three cases. Am J Surg Pathol 1996; 20:156-160.
11. Somogyi L, Kalman E. Metaplastic carcinoma of the penis. J Urol 1998; 160:2152-2153.
12. Bezerra A, Lopes A, Santiago G, Ribeiro K, Latorre M, Villa L. Human papillomavirus as
a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation
and bilateral lymphadenectomy. Cancer 2001; 91:2315-2321.
13. Bezerra A, Lopes A, Landman G, Alencar G, Torloni H, Villa L. Clinicopathologic
features and human papillomavirus dna prevalence of warty and squamous cell carcinoma
of the penis. Am J Surg Path 2001; 25:673-678.
14. Ferreux E, Lont A, Horenblas S, et al. Evidence for at least three alternative
mechanisms targeting the p16INK4A/cyclin D/Rb pathway in penile carcinoma, one of which
is mediated by high-risk human papillomavirus. J Path 2003; 201:109-118.
15. Gross G, Pfister H. Role of human papillomavirus in penile cancer, penile intraepithelial
squamous cell neoplasias and in genital warts. Med Micro Immunol 2004; 193:35-44.
16. Rubin M, Kleter B, Zhou M, et al. Detection and typing of human papillomavirus DNA in
penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am
J Path 2001; 159:1211-1218.
17. Bain L, Geronemus R. The association of lichen planus of the penis with squamous cell
carcinoma in situ and with verrucous squamous carcinoma. J Derm Surg Oncol 1989;
15:413-417.
18. Velazquez E, Cubilla A. Lichen sclerosus in 68 patients with squamous cell carcinoma of
the penis: frequent atypias and correlation with special carcinoma variants suggests a
precancerous role. Am J Surg Path 2003; 27:1448-1453.
19. Powell J, Robson A, Cranston D, Wojnarowska F, Turner R. High incidence of lichen
sclerosus in patients with squamous cell carcinoma of the penis. B J Derm 2001; 145:85-89.
98
20. Johnson D, Lo R, Srigley J, Ayala A. Verrucous carcinoma of the penis. J Urol 1985;
133:216-218.
21. Lopes A, Hidalgo G, Kowalski L, Torloni H, Rossi B, Fonseca F. Prognostic factors in
carcinoma of the penis: multivariate analysis of 145 patients treated with amputation and
lymphadenectomy. J Urol 1996; 156:1637-1642.
22. Sarin R, Norman A, Steel G, Horwich A. Treatment results and prognostic factors in 101
men treated for squamous carcinoma of the penis. Int J Rad Oncol Biol Phys 1997; 38:713722.
23. Slaton J, Morgenstern N, Levy D, et al. Tumor stage, vascular invasion and the
percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph
node metastasis in penile squamous cancer. J Urol 2001; 165:1138-1142.
24. Emerson R, Ulbright T, Eble J, Geary W, Eckert G, Cheng L. Predicting cancer
progression in patients with penile squamous cell carcinoma: the importance of depth of
invasion and vascular invasion. Modern Path 2001; 14:963-968.
25. Ravi R. Correlation between the extent of nodal involvement and survival following groin
dissection for carcinoma of the penis. Br J Urol 1993; 72:817-819.
26. Srinivas V, Morse M, Herr H, Sogani P, Jr WW. Penile cancer: relation of extent of nodal
metastasis to survival. J Urol 1987; 137:880-882.
27. Solsona E, Iborra I, Rubio J, Casanova J, Ricos J, Calabuig C. Prospective validation of
the association of local tumor stage and grade as a predictive factor for occult lymph node
micrometastasis in patients with penile carcinoma and clinically negative inguinal lymph
nodes. J Urol 2001; 165:1506-1509.
28. Lopes A, Bezerra A, Pinto C, Serrano S, de Mello C, Villa L. p53 as a new prognostic
factor for lymph node metastasis in penile carcinoma: analysis of 82 patients treated with
amputation and bilateral lymphadenectomy. J Urol 2002; 168:81-86.
29. de Kerviler E, Ollier P, Desgrandchamps F, et al. Magnetic resonance imaging in
patients with penile carcinoma. Br J Radiol 1995; 68:704-711.
30.Lont A, Besnard A, Gallee M, van Tinteren H, S H. A comparison of physical examination
and imaging in determining the extent of primary penile carcinoma. BJU Int 2003; 91:493495.
31. Algaba F, Horenblas S, Pizzocaro-Luigi Piva G, Solsona E, Windahl T. EAU guidelines
on penile cancer. European Urol 2002; 42:199-203.
32. Horenblas S. Lymphadenectomy for squamous cell carcinoma of the penis. Part 1:
diagnosis of lymph node metastasis. BJU Int 2001; 88:467-472.
33. Windahl T, Andersson S. Combined laser treatment for penile carcinoma: results after
long-term followup. J Urol 2003; 169:2118-2121.
99
34. van Bezooijen B, Horenblas S, Meinhardt W, Newling D. Laser therapy for carcinoma in
situ of the penis. J Urol 2001; 166:1670-1671.
35. Tolia B, Castro V, Mouded I, Newman H. Bowen's disease of shaft of penis. Successful
treatment with 5-fluorouracil. Urology 1976; 7:617-619.
36. Micali G, Nasca M, Tedeschi A. Topical treatment of intraepithelial penile carcinoma with
imiquimod. Clin Exp Dermatol 2003; 28:4-6.
37. Orengo I, Rosen T, Guill C. Treatment of squamous cell carcinoma in situ of the penis
with 5% imiquimod cream: a case report. J Am Acad Derm 2002; 47:S225-228.
38. Schroeder T, Sengelmann R. Squamous cell carcinoma in situ of the penis successfully
treated with imiquimod 5% cream. J Am Acad Derm 2002; 46:545-548.
39. Pehoushek J, Smith K. Imiquimod and 5% fluorouracil therapy for anal and perianal
squamous cell carcinoma in situ in an HIV-1-positive man. Arch Derm 2001; 137:14-16.
40. Smith K, Germain M, Skelton H. Squamous cell carcinoma in situ (Bowen's disease) in
renal transplant patients treated with 5% imiquimod and 5% 5-fluorouracil therapy. Dermatol
Surg 2001; 27:561-564.
41. Mohs F, Snow S, Messing E, Kuglitsch M. Microscopically controlled surgery in the
treatment of carcinoma of the penis. J Urol 1985; 133:961-966.
42. Pyrhonen S, Maiche A, Mantyjarvi R. Verrucous carcinoma of the penis successfully
treated with interferon. Br J Urol 1991; 68:102-104.
43. Maiche A, Pyrhonen S. Verrucous carcinoma of the penis: three cases treated with
interferon-alpha. Br J Urol 1997; 79:481-483.
44. Cardamakis E, Relakis K, Ginopoulos P, et al. Treatment of penile intraepithelial
neoplasia (PIN) with interferon alpha-2a, CO2 laser (vaporization) and 5-fluorouracil 5% (5FU). Eur J Gyneacol Oncol 1997; 18:410-413.
45. Cupp M, Malek R, Goellner J, Smith T, Espy M. The detection of human papillomavirus
deoxyribonucleic acid in intraepithelial, in situ, verrucous and invasive carcinoma of the
penis. J Urol 1995; 154:1024-1029.
46. Ouban A, Dellis J, Salup R, Morgan M. Immunohistochemical expression of Mdm2 and
p53 in penile verrucous carcinoma. Ann Clin Lab Sci 2003; 33:101-106.
47. Dianzani C, Bucci M, Pierangeli A, Calvieri S, Degener A. Association of human
papillomavirus type 11 with carcinoma of the penis. Urology 1998; 51:1046-1048.
48. Michelman F, Filho A, Moraes A. Verrucous carcinoma of the penis treated with
cryosurgery. J Urol 2002; 168:1096-1097.
49. Carson T. Verrucous carcinoma of the penis. Successful treatment with cryosurgery and
topical fluorouracil therapy. Arch Derm 1978; 114:1546-1547.
100
50. Gomez De La Fuente E, Castano Suarez E, Vanaclocha Sebastian F, Rodriguez-Peralto
J, Iglesias Diez L. Verrucous carcinoma of the penis completely cured with shaving and
intralesional interferon. Dermatology 2000; 200:152.
51. Sheen M, Sheu H, Huang C, Wang Y, Chai C, Wu C. Penile verrucous carcinoma
successfully treated by intra-aortic infusion with methotrexate. Urology 2003; 61:1216-1220.
52. Opjordsmoen S, Fossa S. Quality of life in patients treated for penile cancer. A follow-up
study. Br J Urol 1994; 74:652-657.
53. Lindegaard J, Nielsen O, Lundbeck F, Mamsen A, Studstrup H, von der Maase H. A
retrospective analysis of 82 cases of cancer of the penis. Br J Urol 1996; 77:883-890.
54. Agrawal A, Pai D, Ananthakrishnan N, Smile S, Ratnakar C. The histological extent of
the local spread of carcinoma of the penis and its therapeutic implications. BJU Int 2000;
85:299-301.
55. Frimberger D, Hungerhuber E, Zaak D, Waidelich R, Hofstetter A, Schneede P. Penile
carcinoma. Is Nd:YAG laser therapy radical enough?. J Urol 2002; 168:2418-2421.
56. Danczak-Ginalska Z. Treatment of penis carcinoma with interstitially administered
iridium; comparison with radium therapy. Recent Res Cancer Res 1977; 60:127-134.
57. Kiltie A, Elwell C, Close H, Ash D. Iridium-192 implantation for node-negative carcinoma
of the penis: the Cookridge Hospital experience. Clin Oncol 2000; 12:25-31.
58. Crook J, Grimard L, Tsihlias J, Morash C, Panzarella T. Interstitial brachytherapy for
penile cancer: an alternative to amputation. J Urol 2002; 167:506-611.
59. Zouhair A, Coucke P, Jeanneret W, et al. Radiation therapy alone or combined surgery
and radiation therapy in squamous-cell carcinoma of the penis? Eur J Cancer 2001; 37:198203.
60. Fisher H, Barada J, Horton J. Neoadjuvant therapy with cisplatin and 5-fluoruracil for
stage III squamous cell carcinoma of the penis. Acta Oncol 1990; 27:A652.
61. Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate
for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncologica 1988;
27:823-824.
62. Morton D, Wen D, Wong J, al: e. Technical details of intraoperative lymphatic mapping
for early stage melanoma. Arch Surg 1992; 127:392-399.
63. Cabanas R. An approach for the treatment of penile cancer. Cancer 1977; 39.
64. Horenblas S, Jansen L, Meinhardt W, Hoefnagel C, de Jong D, Nieweg O. Detection of
occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node
procedure. J Urol 2000; 163:100-104.
65. Tanis P, Lont A, Meinhardt W, Olmos R, Nieweg O, Horenblas S. Dynamic sentinel node
biopsy for penile cancer: reliability of a staging technique. J Urol 2002; 168:76-80.
101
66. Lont A, Horenblas S, Tanis P, Gallee M, van Tinteren H, Nieweg O. Management of
clinically node negative penile carcinoma: improved survival after the introduction of
dynamic sentinel node biopsy. J Urol 2003; 170:783-786.
67.Kroon B, Horenblas S, Estourgie S, Lont A, Valdes Olmos R, Nieweg O. How to avoid
false-negative dynamic sentinel node procedures in penile carcinoma. J Urol 2004;
171:2191-2194.
68.Ornellas A, Seixas A, de Moraes J. Analyses of 200 lymphadenectomies in patients with
penile carcinoma. J Urol 1991; 146:330-332.
69.Ornellas A, Seixas A, Marota A, Wisnescky A, Campos F, JR dM. Surgical treatment of
invasive squamous cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol
1994; 151:1244-1249.
70.Hussein A, Benedetto P, Sridhar K. Chemotherapy with cisplatin and 5-fluorouracil for
penile and urethral squamous cell carcinomas. Cancer 1990; 65:433-438.
102
APPENDIX 1- Referral proforma:
NORTH THAMES SUPRA-REGIONAL PENILE CANCER CENTRE
Lead Clinician: Mr Suks Minhas, Consultant Urological Surgeon
Penile cancer Nurse Specialist: Clare Akers Tel : 07852 219921 email: [email protected]
Penile cancer MDT Coordinator: Dele Oyebo: email: [email protected]
PA / enquiries: Jane Bradley: Tel: 0207 380 9280 Fax: 0207 380 9303 email: [email protected]
Address for correspondence: Urology Directorate, 2A Maple House, c/o Rosenheim Wing, Grafton Way, London, WC1E 5DB
PENILE CANCER / SUSPICIOUS LESION REFERRAL PROFORMA
Dear Mr Minhas
Please could you see this gentleman who has a suspected penile cancer / suspicious penile
lesion: (delete as appropriate):
Name:
DOB:
Referring hospital number:
Address:
Home and Mobile telephone numbers:
GP details:
Clinical presentation:
Co-morbidity & Medication:
Biopsy/Histopathology:
Imaging performed / results:
Many thanks
[Name of referring clinician]
[Contact details for correspondence]
103
Appendix 2
North West London
Testicular Cancer Supranetwork MDT
Testicular Cancer Clinical Management Guidelines
Supranetwork Policies
Operational Policy 2010
104
North West London
Testicular Cancer Supranetwork MDT
MDT Operational Policy / Clinical Management Guidelines
2009/10
Agreement Cover Sheet
Position:
Lead Clinician, Testicular Supranetwork MDT
Name:
Dr Philip Savage
Signature:
Date Agreed:
Position:
NSSG Chair, Testicular Supranetwork MDT
Name:
Dr Philip Savage
Signature:
Date Agreed:
Position:
Trust Lead Clinician
Name:
Dr. Mark Glaser
Organisation:
Imperial College Healthcare NHS Trust
Date Agreed:
The MDT members agreed the Supranetwork Guidelines/Operational Policy on:
Date Agreed:
Operational Policy Review Date:
West London Testicular Cancer Supranetwork MDT
Operational Policy /Clinical Guidelines
105
Contents
Reference #
Subject
1.0
Introduction
2.0
Structure of the West London Testicular Cancer Supranetwork
MDT Group
 Local Team
 Specialist Team
 Supranetwork Team
3.0
DoH guidelines regarding the roles of the teams within the
Supranetwork
 Local MDT
 Specialist
 Supranetwork
4.0
Membership of the West London Testicular Cancer
Supranetwork MDT



Leadership Arrangements
Core Membership Arrangements
Meeting of the Supranetwork MDT
5.0
Supranetwork Oncology Treatment Centres, Medical
Oncologists and Clinical Oncologists
6.0
Key locations within the West London Testicular Cancer
Supranetwork MDT
Information sources for Testicular Cancer Management
Guidelines
7.0
Page #
8.0
West London Testicular Cancer Supranetwork Initial
Management Guidelines
 Initial Presentation
 Initial Assessment
 Initial Urological Investigations
 Presentation and Oncology referral of advanced
disease/high risk patients
9.0
Urological Surgical Management
 Orchidectomy
 Testicular Prosthesis
 Contra-indications to initial Orchidectomy
 Contralateral Testis Management
 Indications for Consideration of Partial Orchidectomy
 Post-Orchidectomy Care and Investigations
10.0
Referral to the Oncology Team
 Mechanisms and security of referrals
 Supranetwork Policy on Pathological Assessment and
Review
 British and WHO Pathology Classifications
 Policy on Discussion at the Specialist/Supranetwork
MDT
 Supranetwork Policy on communication of the diagnosis
106

to the patients GP
Supranetwork Policy on written information to GP’s of
timeliness and appropriateness of urgent cancer
referrals
11.0
Oncology Investigations
 Key Workers and Records of Consultations
 Supranetwork Policy on Routine Staging Investigations
for Testicular Cancer
 Standard Oncological Staging Investigations
 CXH tumour marker follow-up service
 Background information on tumour markers in Testicular
cancer
12.0
Staging
 Testicular Germ Cell Tumours RMH Staging System
13.0
Supranetwork Policies in the Management of Stage I Germ Cell
Tumours of the Testis
 Important note re Stage IM
 Stage I Seminoma
 Stage I NSGCT
 Stage I mixed Seminoma/NSGCT
14.0
Supranetwork Policies in the Management of Advanced Germ
Cell Tumours of the Testis
 Advanced Disease Pre-treatment Investigations
 IGCCCG Prognostic Groups and Historical Cure Rates
 Seminoma Stage IIA/IIB
 Seminoma Stage IIC/IV
 Management of Advanced NSGCT
 IGCCCG Good Prognosis group
 IGCCCG Intermediate Prognosis group
 IGCCCG Poor Prognosis group
 Special considerations
 Brain metastases
15.0
Supranetwork Recommendations for Relapsed Disease or
Refractory Disease
 Seminoma
 NSGCT
 High dose therapy and PBSCT at Hammersmith Hospital
 Supranetwork Treatment Recommendations for High
Dose Chemotherapy and PBSCT
 Late relapse of Testicular Germ Cell Tumours
16.0
Retroperitoneal Lymph node dissection (RPLND) in Testicular
Cancer
 Supranetwork Treatment Recommendations for
consideration of RPLND after chemotherapy
 Supranetwork MDT and Surgical Location and Personnel
17.0
Trials, Research, Audit and Datasets by the Supranetwork MDT
107
18.0
DoH Recommendations not addressed by the Supranetwork
MDT document
Appendix #
Appendix Subject
1.
NSSG Attendance Summary
2.
Testicular MDT Core Team Attendance 2009/10
3.
Minutes of Annual MDT Operational Meeting
4.
Collaborative Audit of Network Referrals and Attendance List of Meeting
5.
MDT Discussion Proforma
6.
GP Communication Audit
7
Key Worker Policy
8
Details of core nurse members specialist study
9
Written Confirmation of Agreement to Core Nurse Responsibilities
10
Urology SMDT Patient Leaflet
11
Anonymised GP diagnosis Letter
12
Testicular Patient Survey 2010
13
Network Audit
14
Attendance at Communications Skills Course
15
Network Agreed Cancer Minimum Data Set
16
Sperm Storage – Patient Information Leaflet
17
Network Urology Clinical Trials 2009/10
18
Testicular Remedial Action Plan
19
Urology Summary
20
Urology Checklist
21.1
Oncology Referral Proforma
21.2
Pathology Request letter
22.0
Oncology Checklist
23.1
Stage I seminoma RT protocol
23.2
Stage I seminoma Surveillance Protocol
23.3
Stage I seminoma Follow up after adjuvant treatment
23.4
Stage I NSGCT Surveillance Protocol
24.1
Staging IGCCCG prognostic groups and Recommended treatments
24.2
Sperm storage Information
24.3
Sperm storage request letter
24.4
Stage IIA Seminoma RT
24.5
1st line Chemotherapy regimens
108
24.6
Advanced GCT post chemotherapy follow-up protocols
25.1
Urology Support folder
25.2
Oncology Support folder
109
1.0
Introduction
Germ cell tumours of the testis are the most common malignancy in young men with an
observed 88% rise in the incidence over the past 25 years1. Fortunately, modern expert
management leads to extremely high cure rates; 99% in stage I and 90%, 75-80% and 50%
respectively in advanced disease with the ‘good’, ‘intermediate’ and ‘poor’ prognostic
criteria2.
As a result of work over the past 30 years, germ cell tumours have become the ‘model’ of
curable cancer. The major factor for the high cure rate, in advanced testicular cancer, is the
high level of sensitivity to chemotherapy, however advances in surgery, radiotherapy and
chemotherapy support have helped produce the current favourable situation.
As a rare illness that can require complicated treatment, most expert opinion supports the
centralisation of care for testicular cancer in centres of excellence. To support this opinion
there have been important publications demonstrating superior outcomes including higher
survival for patients treated in regional centres rather than local hospitals3, 4.
This move towards centralisation of expert care is well established in the UK and the
introduction of national and international management guidelines such as those published
by COIN5 and the EGCCCG1 have further helped support high levels of clinical care.
The steps to enhance the organisational aspect of testicular cancer care in the UK have
included the publication of guidance in the NICE ‘Improving Outcomes in Urological
Cancers’ manual6 and more recently the DoH guidance on the structure, organisation and
workings of local, network and Supranetwork testicular cancer management groups.
This document outlines the structure, working arrangements and patient management
policies of the West London Testicular Cancer Supranetwork MDT. This group is based on
the oncology treatment centres of Charing Cross Hospital, Chelsea and Westminster
Hospital and Mount Vernon Hospital and the various urology surgery units.
1 BJU Int. 87(4):361-5
2 Annals of Oncology 2004 15(9):1377-1399
3 BJC 72:1303-1306
4 JNCI 91:839-846
5 Clinical Oncology 12:S173-209
6 NICE Website
110
2.0
Structure of the West London Testicular Cancer Supranetwork MDT
Organisational Structure
The organisation of care for patients with testicular cancer in West London is based on that
outlined DoH document. It may be helpful to briefly recap the various terms involved and
the expectation of their role in provision of care within the Supranetwork.
Local Urology team
Essentially this is each local hospital and the team providing the service there.
In terms of testicular cancer service provision it is anticipated that the local urology team
will perform the majority of orchidectomies.
Specialist Urology team
To host a specialist urology team requires a catchment population of at least 1 million. This
team looks after the radical surgical aspects of specialist care which should all be done in
the host hospital.
The Supranetwork includes three specialist urology teams based on Charing Cross
Hospital, Chelsea and Westminster Hospital/St Mary’s and Mount Vernon.
Supranetwork Testicular team
The Supranetwork requires a minimum catchment population of 2 million. The
Supranetwork catchment area covers the areas served by the listed Hospital/Urology
teams. As a result of the historical strengths of the units and difficulties in travel for patients
in West London the Oncology treatment takes place at all 3 centres.
Within the Supranetwork there is a single site for RPLND and a single site for High Dose
Chemotherapy and PBSCT.
Local Urology Units
Charing Cross Centre
Chelsea and Westminster Centre
Charing Cross Hospital
Chelsea and Westminster Hospital
Ealing Hospital
St Mary’s Hospital
Hammersmith Hospital
Wexham Park Hospital
West Middlesex Hospital
Northwick Park Hospital
Mount Vernon Centre
Central Middlesex Hospital
Lister Hospital Stevenage
Barnet General Hospital
Queen Elizabeth Hospital, Welwyn
Hillingdon Hospital
Luton and Dunstable Hospital
Amersham Hospital
Hemel Hempstead Hospital
Wycombe Hospital
St Albans Hospital
Heatherwood Hospital
Watford General Hospital
Watford General Hospital
111
Specialist Treatment Centres
Chemotherapy Treatment and Surveillance Centres
Charing Cross Hospital
Chelsea and Westminster Hospital
Mount Vernon Hospital
RPLND Surgical Centre
Charing Cross Hospital
High Dose Chemotherapy In-Patient Treatment Centre
Hammersmith Hospital
Radiotherapy
Charing Cross Hospital
Mount Vernon Hospital
Tumour Marker Registration and Surveillance
GTT office and SupraRegional Assay Service centre at Charing Cross Hospital
3.0
DoH and West London Supranetwork guidelines regarding the roles of the teams
within the Supranetwork
The DoH guidelines re Local Care
This consists of:
a) Diagnosis of all cases and
b) Orchidectomy for non-high risk patients
Orchidectomy may be performed under the care of any urologist, not just those who are
members of urological cancer MDTs.
The DoH guidelines re Specialist Care
This should be defined and agreed by each network as follows:
Referral guidelines should be agreed by each urological network site-specific group
(NSSG) in consultation with their relevant testicular cancer Supranetwork.
The referral guidelines should determine:
a) Regarding radiotherapy for seminoma; which categories of patients may be given
radiotherapy under the care of one of a list of agreed specialist teams in the network and
which categories of patients should be treated only by the Supranetwork team.
b) The agreed list of named specialist teams, referred to in the paragraph above.
c) Regarding chemotherapy for germ cell cancer; an agreed list of named specialist teams
in the network which may treat stage I and 'good prognosis' metastatic cases.
d) The specific parameters which define 'good prognosis' as referred to in the paragraph
above.
The DoH guidelines re Supranetwork Care
This should only be given by the relevant Supranetwork testicular cancer team and
consists of:
a) Orchidectomy on high risk patients referred pre-operatively.
b) Surgical resection of post-chemotherapy residual masses. (It may be considered
appropriate for only a small number of Supranetwork teams to offer this in the country).
c) Treatment of all post radiotherapy and post chemotherapy recurrences. (Treatment of
first recurrences occurring during surveillance should follow the network's agreed
guidelines as for newly diagnosed cases, depending on parameters of disease stage and
type.)
112
d) All other treatment by any modality, excluding local care and the network's particular
arrangements for specialist care.
North West London Supranetwork Policy
It is the policy that, with the exception of diagnosis and simple orchidectomy for presumed
stage I disease, no other treatment or follow-up is to be delivered ‘locally’.
The limited geographical distances and the layout of oncology provision within the
Supranetwork layout means that there is no ‘specialist’ treatment centres for testicular
cancer. All the detailed assessment, follow up, chemotherapy, radiotherapy and complex
surgery is to be delivered within the core central hospitals of the Supranetwork as detailed
on page7.
4.0
Membership of the West London Testicular Cancer Supranetwork MDT
Leadership arrangements( 08-2G-301)
Dr Philip Savage, Consultant Medical Oncologist, is the lead clinician of the Supranetwork
MDT. His role and responsibility is to ensure that the following objectives of MDT working
(as laid out in Manual of Cancer Services) are met:

Ensure that designated specialists work effectively together in teams such that decisions
regarding all aspects of diagnosis, treatment and care of individual patients and decisions
regarding the team’s operational policies are multidisciplinary decisions

Ensure that care is given according to recognised guidelines (including guidelines for
onward referrals) with appropriate information being collected to inform clinical decision
making and to support clinical governance/audit

Ensure mechanisms are in place to support entry of eligible patients into clinical trials,
subject to patients giving fully informed consent

Overall responsibility for ensuring that MDT meeting and team meet peer review quality
measures;

Ensure attendance levels of core members are maintained, in line with quality measures

Ensure that target of 100% of cancer patients discussed at the MDT is met;

Provide link to NSSG either by attendance at meetings or by nominating another MDT
member to attend

Lead on or nominate lead for service improvement

Organise and chair annual meeting examining functioning of team and reviewing
operational policies and collate any activities that are required to ensure optimal functioning
of the team (e.g. training for team members)

Ensure MDT’s activities are audited and results documented;

Ensure that the outcomes of the meeting are clearly recorded and clinically validated and
that appropriate data collection is supported

Ensure target of communicating MDT outcomes to primary care is met.
113
Memberships arrangements (08-3G-302 / 08-3G-306)
Please find below the Core Membership and Cover arrangements for the Testicular
Supranetwork MDT
NAME
Dr Philip Savage
Prof Michael Seckl
Dr Cathryn Brock
Prof Gordon Rustin
Dr Alison Falconer
Mr David Hrouda
Mr Bijan Khoubehi
Dr Ethna Manion
Dr Nick Burfitt
Sr Rachel Sharkey
Edward Marshall
Speciality &
Designation
Consultant Medical
Oncologist CXH/Imp
Consultant Medical
Oncologist CXH/Imp
Consultant Medical
Oncologist CW
Consultant Medical
Oncologist MVH
Consultant Clinical
Oncologist CXH/Imp
Consultant
Urological Surgeon
CXH/Imp
Consultant
Urological Surgeon
CXH/Imp
Consultant
Histopathologist
CXH/Imp
Consultant
Radiologist CXH/Imp
Urology Clinical
Nurse Specialist
CXH
MDT coordinator
CXH
MDT roles
Deputy
Chairman
Lead service
improvement
Lead for clinical
trials
Prof Michael Seckl
Dr Philip Savage
Dr Philip Savage
Dr Philip Savage
Lead Clinical
Oncologist
Dr Simon Stewart
Lead RPLND
surgeon
Mr Bijan Khoubehi
Mr David Hrouda
Lead Pathology
clinician
Dr Steven Hazell
Lead Imaging
clinician
Lead for users
issues and
information to
patients and carers
Dr Nadeem Qazi
Sr Jo Sethi
Jenny Mistry
Other arrangements (08-3G-302 / 08-3G-304)
Professor Michael Seckl is responsible for recruiting to clinical trials and Sr Rachael Sharkey is
responsible for users issues. Mr David Hrouda and Mr Bijan Khoubehi, Consultant Surgeons, are
responsible for resection of post-chemotherapy residual masses.
All the above are core members of the Testicular Supranetwork MDT.
Attendance to NSSG Meetings (08-2G-303)
The MDT sends a team member as a representative to a minimum of two thirds of the NSSG
meetings. (Appendix 1 - NSSG Attendance Summary). .
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Extended Membership (08-3G-321)
Name
Mr Simon Carter
Miss Norma Gibbons
Mr James Bellringer
Mr Jonathan Ramsay
Mr Altaf Shamsuddin
Mr Alvan Pope
Mr Paul Abel
Dr Mark Glaser
Dr Steve Mangar
Dr Simon Stewart
Dr Katie Urch
Philip Alexander
Teresa Birkett
Sr Winnie Nugent
Speciality &
Designation
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Clinical Oncologist
Clinical Oncologist
Clinical Oncologist
Consultant in
Palliative Medicine
Psychosexual
counsellor
Social worker
Name
Speciality & Designation
Mr Sanjiv Agarwal
Mr Justin Vale
Mr Anup Patel
Mr Ross Witherow
Mr Tom Rosenbaum
Mr Asif Raza
Mr Bijan Khoubehi
Mr Matt Winkler
Clare Johnson
Caroline Kidd
Mary Turner
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Urological Surgeon
Stoma Nurse
Counsellor
Complementary therapies
Christopher Guiness
Chaplaincy
Tina Smith
Urology CNS CWH
Urology Clinical Nurse
Specialist MVH
Deepa Tailor
MDT coordinator MVH
Meetings of the West London Testicular Cancer Supranetwork MDT (08-3G-305/08-2G-307/
08-2G-308/ 08-3G-309 / 08-2G-310)
 The meetings of the West London Testicular Cancer Supranetwork MDT take place weekly at
Charing Cross Hospital at 9am. The venue is the 8th Floor East wing MDT meeting room and
is video linked with the Mount Vernon meeting.
 All new cancer patients are reviewed by the MDT for discussion of initial treatment plan.
 The core team members and their cover should attend 2/3 of the MDT meetings. Individual
core team members are required to attend at least 50% of the meetings
A register of attendance will be kept by the MDT co-ordinator and audited for compliance
annually. (Appendix 2 - Attendance Audit 09/10)
 An annual meeting to discuss operational policy is held annually. (Appendix 3- MDT Annual
Meeting )
 At the annual meeting the MDT should provide the numbers of new, relapsed and extraSupranetwork patients discussed in the preceding 12 months. The analysis of patient
pathways, clinical trials, audits and review of patient feedback will also be discussed
 The MDT objective includes commitment to IOG compliance, working to agreed NSSG
guidance, undertaking service improvement, participating in audit, including agreed NSSG
audits.
 Supranetwork Collaborative Audit - Annual audit of cases over the previous year, diagnosed
with testicular cancer by it’s referring teams and it’s own cases. The audit will be against the
Network guidelines ‘testicular cancer – referral to another team’ and ‘testicular cancer –
defining specialist care in the Network’. (Appendix 3- MDT Annual Meeting / Appendix 4 –
Patient Pathway Audit )
5.0
Supranetwork Oncology Treatment Centres, Medical Oncologists and Clinical
Oncologists
The policy of the Supranetwork is to work as team with three treatment locations. The
Supranetwork has agreed, in the light of the historical strengths of each centre and the travel
implications for patients, that post orchidectomy surveillance and chemotherapy treatment can be
given at all three sites. For more specialist areas the following arrangements apply:
115




Radiotherapy: Charing Cross and Mount Vernon Hospitals
RPLND Surgery: Charing Cross Hospital
High dose chemotherapy: Hammersmith Hospital (Haematology Department)
First line poor prognosis and Relapsed patients for second line chemotherapy are to be
managed at either Charing Cross Hospital or Mount Vernon Hospital
6.0
Supranetwork Key Locations and Personnel
The details of the 3 Oncology Treatment Centres are:
Oncology Treatment Site
Charing Cross Hospital
Chelsea and Westminster/
St Mary’s Hospital
Mount Vernon Hospital
Med Oncologists
Prof Michael Seckl
Dr Philip Savage
Dr Cathryn Brock
Clinical Oncologist
Dr Alison Falconer
Prof Gordon Rustin
Prof Peter Hoskin
Dr Simon Stewart
Urological Surgery Units
Charing Cross Hospital
Chelsea and Westminster Hospital
Ealing Hospital
St Mary’s Hospital
Hammersmith Hospital
West Middlesex Hospital
Northwick Park Hospital
Lister Hospital Stevenage
Queen Elizabeth Hospital, Welwyn
Luton and Dunstable Hospital
Watford General Hospital
Heatherwood Hospital
Wexham Park Hospital
Central Middlesex Hospital
Barnet General Hospital
Hillingdon Hospital
Amersham Hospital
Wycombe Hospital
Hemel Hempstead Hospital
St Albans Hospital
7.0
Testicular Cancer Clinical Management Guidelines - Information Sources
This document forms a summary of what is regarded by the Supranetwork as good practice and
includes the standards and policies that the Supranetwork will work to.
Further detailed clinical information, national and international guidelines are available;
UK COIN guidelines
http://www.rcr.ac.uk/
EGCCCG 2007 guidelines
European Urology 53;478-496
NIH guidelines (USA)
http://www.cancer.gov/
Another interesting source of information that many patients may use is the TCRC website.
http://tcrc.acor.org/
The Testicular Clinical Management Guidelines have been agreed by the Supranetwork MDT and
can be sourced in the Urology NSSG Clinical Guidelines 2010- Testicular Cancer Clinical
Management Guidelines, pp 169-187 . The following guidelines have been agreed by the NSSG




MDT/Network/Testicular agreed follow up (08-2G-313) - NSSG Clinical Guidelines
pp.171-176
MDT/network/supranetwork agreed referral guidelines for testicular cancer (08-3G-327)NSSG Clinical Guidelines pp 171-176
MDT/network/supranetwork agreed referral guidelines to another team (08-3G-328)
NSSG Clinical Guidelines pp 171-176
MDT/network/supranetwork agreed referral guidelines MDT discussion (08-3G-329)NSSG Clinical Guidelines 171-176.
116


8.0
MDT/network/supranetwork agreed referral guidelines specialist care (08-3G-330)- NSSG
Clinical Guidelines 171-176.
MDT/network/supranetwork agreed referral guidelines for testicular cancer - referral of
histology and radiology (08-3G-331)- NSSG Clinical Guidelines pp.169-187.
Supranetwork Testicular Cancer Initial Management Guidelines
Initial Presentation
The majority (80-90%) of men with testicular cancer present with a testicular mass, other
presentations can include lower back discomfort, a hydrocele or rarely gynaecomastia. The most
common routes to the local hospital urology team are via the GP or casualty.
According to the COIN and DoH guidelines GP referrals should be seen within 2 weeks, however
the aim of the Supranetwork is that all patients with a potential diagnosis of testicular cancer
should be classed as urgent patients. Patients referred from outside the hospital should be seen in
the next clinic of any urologist within the unit and must be seen within a maximum 5 working days.
Initial Urological Assessment
The initial assessment of patients with suspected testicular cancer should include a full history and
clinical examination. The history should include questions regarding, any history of maldescent,
cryptorchism or a family history of testicular cancer.
Initial Urological Investigations
The initial imaging investigation should be a bilateral testicular ultrasound scan. This should report
the dimensions of both testes, the size of any mass and document the presence or absence of
calcification. A chest X-ray should also be performed.
The initial blood tests must include FBC, biochemistry, LDH and the tumour markers AFP and bHCG. Of note AFP or b-HCG can be positive in up to 74% of NSGCT, whilst the b-HCG can be
elevated in 10% of cases of seminoma.
Note re Tumour Markers.
1/ For the rapid assessment of newly presenting patients these initial tumour marker
measurements can be performed in the laboratory of the local hospital.
2/ Urine based hCG pregnancy tests should never be used as a quick screening test for potential
testicular cancer
The role of the urological team in the assessment, investigation and referral policy is summarised
on sheet (Appendix 19 – Urology Summary) which is to be displayed in all Urology outpatients
units with in the Supra-Network. A checklist of the investigations that can be placed in the notes is
included as sheet (Appendix 20- Urology Checklist)
Presentation of Advanced Disease (defined by the Supranetwork MDT as ‘High Risk’
patients)
Approximately 5% of patients present with advanced disease, this may be apparent as a result of
raised tumour markers, para-aortic lymph nodes forming an abdominal mass or symptoms
secondary to distant metastases most commonly in the lungs but occasionally in the CNS or other
sites.
If a patient is suspected of having advanced disease, the case must be discussed with one of the
WLCN Supranetwork medical oncology consultants prior to consideration of orchidectomy. These
patients are frequently optimally treated with urgent chemotherapy and then completing an
orchidectomy at the end of treatment.
Consultant specialist advice regarding the indications for emergency transfer and treatment of
testicular cancer is available from CXH 24 hrs a day each day of the year. Call 0208-846-1234 and
117
ask the operator for the medical oncology SpR on call who can liaise with the
choriocarcinoma/testicular cancer consultant team who provide 24hr cover.
Patients who present with ‘high risk’ or advanced disease will receive chemotherapy treatment
according to their IGCCCG prognostic group. (see section 13). In brief those with good prognosis
disease generally receive 3 cycles of BEP, those with intermediate prognosis disease 4 cycles of
BEP and those with poor prognosis disease are generally treated with 4 cycles of BEP or POMB
ACE chemotherapy.
Patients presenting with end organ failure, particularly respiratory compromise are often treated
with 2 days of low dose EP chemotherapy, prior to the initiation of definitive chemotherapy.
Emergency doses of chemotherapy are available at CXH 24 hours a day every day of the year.
The chemotherapy protocols are detailed in Appendix 24.6.
9.0
Urological Surgical Management
A copy of the network supported surgical management guidelines and referral pathway are
incorporated into the testicular cancer/urology guide supplied to all the urology teams within the
Supranetwork.
Orchidectomy
Orchidectomy is rarely an emergency procedure and patients presenting out of hours should have
surgery performed on the next available day time list.
Radical orchidectomy is to be performed through an inguinal incision. The tumour bearing testicle
is resected along with the spermatic cord at the level of the internal inguinal ring.
Testicular Prosthesis
It is regarded as good practice that patients are offered the possibility of having a testicular
prosthesis fitted. There is some evidence that loss of the testis can result in some psychological
morbidity, however it is unclear how helpful a prosthesis is in coping with this.
It is regarded as good practice by COIN, NICE and the DoH that the option of having a prosthesis
fitted at the time of orchidectomy is discussed and that this discussion and the outcome are
recorded in the notes. Additionally the Supranetwork require that this discussion/outcome is
recorded on the referral form.
It should also be noted that a decision regarding a prosthesis can be deferred and a prosthesis
inserted at a later stage, when there has been greater time for consideration.
Contra-indications to initial orchidectomy
As detailed in section 7, patients who may have advanced testicular cancer should not proceed
directly with a routine orchidectomy. These patients must be discussed with one of the medical
oncology teams directly by phone. Do not wait for the next MDT meeting.
Contralateral Testis Management
Approximately 1.5% of testicular cancer patients develop bilateral disease. Whilst synchronous
presentation with bilateral tumours is rare, a considerable number of patients present with
potentially pre-malignant changes in the contralateral testis.
Whilst there is not yet a consensus on how best to manage these patients with potential premalignant changes a biopsy to look for TIN/CIS can be particularly considered if:
A history of maldescent
Testicular volume <12ml
Multifocal punctate calcification
The option of contralateral testicular biopsy should be discussed with the patients at high risk of
TIN.
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Indications for Consideration of Partial Orchidectomy
This may be an alternative to orchidectomy in small primary tumours, however this approach is
experimental and is not yet part of standard routine practice.
However partial orchidectomy may be considered, following discussion with the patient and the
Supranetwork MDT, in case of patients with:
 Synchronous bilateral testis tumours
 Metachronous contralateral (second) testis tumour
 Tumour in a solitary testis and adequate endocrine function
Post-Orchidectomy Care and Investigations
It is helpful if the tumour markers (LDH, AFP and bHCG) can be repeated post-operatively.
10.0
Referral to Oncology, MDT discussion, Pathology Review Supranetwork procedures
Referral to the oncology team at Charing Cross, Chelsea and Westminster or Mount Vernon
Hospitals should take place on or before the day of the orchidectomy, there is no need to wait for
either the pathology result or for the urological out patient follow-up appointment.
Ensuring the security of the referral should be achieved by a two stage system,
1/ Phoning the oncology teams involved:
CXH
Dr Savage
Prof Seckl
020-3311-1419
020-3311-1421
Chelsea and Westminster
Dr Brock
0208-846-5054
Mount Vernon
Prof Rustin
01923 844389
2/ The patient’s details should be faxed through on the referral proforma sheet (Appendix 21.1)
which should be sent to; Additionally a copy of the fax or a secure email should be sent to the
MDT coordinator at CXH or MVH.
CXH
Dr Savage
020-3313-5577
Prof Seckl
020-3313-5577
Or email
[email protected]
Chelsea and Westminster
Dr Brock
0208-746-8863
Mount Vernon
Prof Rustin
01923 844840
Arrangement and Confirmation of Oncology outpatients appointment and Pathology
Review Request
On receipt of the referral the Oncology team will confirm the date of the first outpatient
appointment for that patient. This information will be relayed to the referring urology team or
directly to the patient. The details of the first appointment and the route this was relayed to the
patient will be recorded in the Oncology notes.
119
Additionally the oncology team will at the point of receipt of the referral send a request for central
review of the pathology to the Histopathology team at the urology unit. A standard letter to
expedite this request is included in (Appendix 21.1 - Pathology Request Letter).
Supranetwork Policy on Pathological Assessment and Review
Germ cell tumours of the testis are not common, and many pathologists do not see a sufficient
number of cases to be fully confident in giving a comprehensive report, which is essential for
further clinical management. The pathology for all patients with suspected testicular cancer should
be referred to one of the oncology treatment centres where the pathology of the tumour should be
reviewed by a pathologist with a special interest and experience in germ cell tumours.
The arrangements for pathology review are that the GTT office at CXH will request the pathology
review from cases outside the 3 main centres at the time of the patient’s registration with the
tumour marker follow-up service at Charing Cross Hospital.
For patients who are not routine cases, such as advanced disease presentations or outside
RPLND patients their pathology review will be requested directly at the MDT meeting
The designated pathologists for germ cell tumours of the testis within the network are;
Chelsea and Westminster Hospital
Dr Marjorie Walker
Dr Jo Lloyd
Charing Cross Hospital
Dr Ethna Mannion -Supranetwork lead histopathologist
Dr TBA
Mount Vernon Hospital
Dr Rowena Smith
Pathology Reporting Standards
The COIN recommendations regarding pathology assessment, reporting and pathological staging
are available in hard copy.
The pathology subtypes as described by both the British and WHO systems and their relationship
with tumour markers are shown below;
British and WHO Pathology Classifications
British
WHO
Seminoma
Seminoma
Spermatocytic seminoma
Spermatocytic seminoma
Teratoma
- teratoma differentiated
- malignant teratoma intermediate (MTI)
- malignant teratoma undifferentiated
(MTU)
- yolk sac tumour
- malignant teratoma trophoblastic
Non seminomatous germ cell tumour
- mature teratoma
- embryonal carcinoma with teratoma
(teratocarcinoma)
- embryonal carcinoma
- yolk sac tumour
- choriocarcinoma
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Supranetwork Policy on Discussion at the Specialist/Supranetwork MDT (08-2G-309 / 08-2G326)
1) It is the policy of the Supranetwork MDT that all cases of testicular cancer must have their case
presented to and discussed at the next meeting of the Supranetwork testicular cancer MDT. The
patients imaging and histopathology must be reviewed by the Supranetwork MDT at the first
opportunity. The recording note keeping of the MDT discussion will include at least; the patient’s
identity, the type of testicular cancer, the staging, the treatment plan and the identity of the key
worker. In the cases of patients referred for resection of post-chemotherapy masses to a team in
another Network, the team to which they are referred will be named.
(Appendix 5 – MDT Discussion Proforma)
2) For patients who need an urgent treatment planning decision between Supranetwork meetings,
the recommendation is that this is made via phone calls and the outcome recorded in the case
notes. It is likely that the majority of cases will concern issues regarding Oncological treatment, in
these cases the Consultant in Charge should discuss with one of the (other) WLCN Supranetwork
consultant medical oncologists. If the urgent treatment concerns a surgical issue, the Consultant in
Charge should discuss with one of the Supranetwork Urologists.
It should be noted that routine orchidectomy in non-high risk patients does not have to be
discussed in advance by the Supranetwork
To ensure that all cases are reviewed, referral faxes and letters should be copied to the MDT coordinators. The MDT co-ordinators will also liaise with the Oncology teams prior to the meeting to
ensure all cases are included.
Supranetwork Policy on communication of the diagnosis to the patients GP (08-3G-311)
It is the policy of the Supranetwork that the diagnosis is relayed to the GP within 24hrs of the
patient being informed. Following discussions at the MDT the patient GP is informed within 24
hours of the diagnosis and treatment plan by Fax or secure email via NHS mail.
As part of the Supranetwork requirements we are required to perform an audit of the timeliness of
notification to the GP so it is essential that a copy of this correspondence is kept. The audit will be
performed annually and presented to the PCTs. (GP Communication Audit available in hard
copy)
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11.0
Oncology Investigations
To help with the initial Oncological assessment a Proforma is included in (Appendix 22 Oncology Checklist). The Proforma gives a list of all the standard investigation and space to
include information about the identification of the Key Worker and the discussion regarding any
permanent records of consultations. Additionally the Proforma includes a check to ensure that the
pathology review has (already) been requested.
Key Worker (08-2G-312)
It is the policy of the Supranetwork that at the time of the patients first attendance at the Oncology
unit that the patient is informed of their key worker. It is the responsibility of the Core team CNS to
identify and ensure the name and contact number is in the notes. It is the role of the key worker to
co-ordinate the patients care, promote continuity and ensure the patient know who to access for
information and advice. It is the expectation of the MDT that the Consultant Oncologist of the
patient will be the key worker for the majority of patients. The key worker is supported by the
clinical nurse specialist at each site, who is able to take an active role in the care and support of
any patients with additional needs.(Appendix 7 – Key Worker Policy)
Role of the Clinical Nurse Specialist
The role of specialist nurses at ICHT is key to the successful management of patients with
Urological cancer. Several different types of nurse play a part including:
Core Nurse Member Completed Specialist Study (08-2G-317)
The MDT should have at least one core nurse specialist who should have successfully completed
a programme of study in their specialist area of nursing practice, which has been accredited for at
least 20 credits at fist degree level or equivalent. (Appendix 8 – Details of Core Nurse Members
Specialist Study)
Responsibilities for Core Nurse Members (08-2G-318/319)
Rachel Sharkey is the Clinical Nurse Specialist for the Testicular Supranetwork MDT. Her cover is
Joanne Sethi. (Appendix 9 – Written Confirmation Core Nurse Responsibilities)
Patient Information (08-2G-316/325)
Below are details of the type of information offered to patients. The offering of this information is
identified within the patient notes. This should include as a minimum information on:
- local provision of services
- self help groups
- psychological, social and spiritual/cultural support available
- specific disease information and treatment options
- sperm storage facilities for testicular cancer
(Appendix 16 - Sperm Storage Patient Information leaflet)
(Appendix 10 – Urology SMDT Patient Leaflet)
Access to MDT members
Written contact details for relevant MDT members will be provided to patients and their carers, and
maintained up to date. (See IHUCC Leaflet for patients on diagnosis ‘The Urology Cancer
Specialist Multidisciplinary Team’) (Appendix 10 – Urology SMDT Patient Leaflet)
Permanent Record of Consultation (08-3G-322)
It is a policy of the Supranetwork MDT that all patients have the opportunity to receive a
permanent record of their first and any subsequent consultation. The letters will include the details
of the diagnosis, staging and treatment options. At present this is achieved via a request for copies
of any/all clinical letters and additionally patients may request a tape recording of any out-patient
122
consultation. However tape recordings are not made routinely and the MDT will need advance
notice of this requirement. These requests can be to the Consultant in charge, their secretary or
via the patient’s key worker.
(Appendix 11- Anonymous GP Diagnosis Letter)
Patient Feedback (08-3G-323/324)
The Supranetwork will produce an annual survey of the patient’s experience of the services
offered by the Supranetwork MDT
 The survey will include the following questions as a minimum
 If the patient was offered a key worker
 The provision of information for patients/carers
 The offering of an opportunity for a permanent record of consultation
 Further question can be added as wished by the MDT

(Appendix 12 - Patient Survey / Appendix 3- Testicular Supranetwork MDT Annual Meeting)
Communications Skills Course (08-2G-320)
At least those core members of the team who have direct clinical contact with patients should have
attended the national advanced communications skills training Rachel Sharkey, Clinical Nurse
Specialist and Dr Cathryn Brock, Medical Oncologist have attended the Course and the remaining
core team who have direct patient contact have submitted their names for future courses in
2011/12.(Appendix 14 – Attendance at Advanced Communication Skills Course).
Supranetwork Policy on Routine Staging Investigations for Testicular Cancer
The policy of the Supranetwork group is for most of the post orchidectomy staging investigations to
be performed at the Oncology treatment centre. In particular the staging CT scan in patients who
do not clinically appear to have advanced disease should be performed by their Oncology team at
their treatment centre. However the patients LDH and tumour markers should be checked post
operatively at the urology unit if the patient remains an in-patient for more than 1 day.
Standard Oncological Staging Investigations
For patients with presumed stage I disease the standard post operation staging investigations
should comprise;
CT Thorax Abdomen and Pelvis
CXR
hCG/AFP/LDH
Full blood count
Biochemistry
Central review of pathology
Sperm storage (08-2G-315/ 08-3G-316)
It is the policy of the Supranetwork that all patients are to be offered the opportunity for sperm
storage. This is generally performed post orchidectomy, however in selected patients preorchidectomy sperm storage should be considered if there are concerns re the sperm production
potential from the contralateral testis.
All stage I surveillance patients who go on to require chemotherapy or radiotherapy treatment
should be offered sperm storage prior to treatment if this was not done previously.
123
Sperm storage for Supranetwork is performed at Hammersmith Hospital in the Andrology unit.
Patients should be advised that negative tests for HIV, HEP B and C are required for long term
storage. At present sperm storage is routinely funded by the PCTs.
The Testicular Team provide information on sperm storage in general as well as contact
arrangements specific to the facilities available.
(Appendix 16 - Sperm Storage Patient Information leaflet / Appendix 24.2 - Sperm Strorage
Information/ Appendix 23.4 – Sperm Storage request letter )
Charing Cross Hospital tumour marker follow-up service
All patients within the Supranetwork with testicular cancer are to be registered with the Charing
Cross Hospital tumour marker follow-up service irrespective of their tumour marker status.
This system ensures that marker follow-up is co-ordinated with the protocols particularly in the first
6 months of treatment when marker follow-up testing is more frequent than the monthly clinic visit.
The SupraRegional Tumour marker assay service will provide, the results, automatic alerts,
reminders and relevant analysis of the patients tumour markers (hCG, AFP, LDH)
Contact details of the Charing Cross marker follow-up service
Tel 020-3311-1409
Fax 020-3383-5577
Please use form APP
Background information on tumour markers in Testicular cancer
The table below shows the approximate incidence of marker production in the differing pathology
types in germ cell tumours. However it should be noted also that the pattern of marker production
can alter with progression of the disease as the results of the study shown below confirms;
Histology of Primary Germ Cell Tumours and Frequency of Serum Tumour Markers
Presence of tumour markers by cell type
(%)
Tumour type
All germ cell tumours
Seminoma
Nonseminomatous germ
cell tumours
Embryonal cell carcinoma
Teratocarcinoma
Teratoma
Choriocarcinoma
Yolk sac
Frequency by cell
type (%)
AFP
HCG
100
42
58
50 to 75
0
65
40 to 60
9
56
26
26
5
1
<1
70
64
37
0
75
60
57
25
100
25
AFP=alpha-fetoprotein serum half life 3-5 days; HCG=human chorionic gonadotropin serum
half life 1-2 days.
124
The value and limitations of markers in the diagnosis of recurrent disease.
For more information see Trigo et al; Cancer 2000; 88 162-8
Records of 794 patients with GCTs
123 went on to relapse
12/36 seminoma were marker positive
67/87 teratoma were marker positive
At diagnosis of relapse
Seminoma
36 patients relapsed of whom 16 were marker positive (10 who had been hCG positive at initial
diagnosis and 6 who were initially marker negative)
NSGCT
87 patients relapsed of whom 60 were marker positive (48 who had been hCG positive at initial
diagnosis and 12 who were initially marker negative). The paper also showed that patients who
were marker +ve at diagnosis can relapse with marker –ve disease.
Conclusion
Overall the pattern at diagnosis and relapse only correlated in 56 of the 87 pts (64%)
Markers need to measured in all GCT patients as per protocols and can be of value in both pts
with disease that is initially marker + ve and marker –ve.
12.0
Testicular Germ Cell Tumours Staging System
Whilst the management of advanced testicular cancer is mainly determined by the IGCCCG
prognostic grouping. When appropriate the Supranetwork also uses the Royal Marsden Staging
system as shown below
RMH Staging
I No evidence of disease outside the testis
IM As above but with persistently raised tumour markers
II Infradiaphragmatic nodal involvement
IIA Maximum diameter <2 cm
IIB Maximum diameter 2-5 cm
IIC Maximum diameter >5-10 cm
IID* Maximum diameter >10 cm
III Supra and infradiaphragmatic node involvement
Abdominal nodes A, B, C, as above
Mediastinal nodes M+
Neck nodes N+
IV Extralymphatic metastases
Abdominal nodes A, B, C, as above
Mediastinal or neck nodes as for stage 3
Lungs:
 L1 <3 metastases
 L2 Multiple metastases <2 cm maximum diameter
 L3 Multiple metastases >2 cm in diameter
Liver involvement H+
Other sites specified
125
13.0
Supranetwork Policy Management of Stage I Germ Cell Tumours of the Testis
Important note re Stage IM
Stage IM is actually advanced disease and requires chemotherapy treatment, not standard stage I
disease management.
Stage I Seminoma
Natural History
Without adjuvant treatment the risk of relapse from stage I seminoma is ~ 17-20%, with a median
time to relapse of 1.5 years. However late relapses are not unusual, with 13.5% of relapses
occurring beyond 5 years. The risk of relapse seen in the MRC study after adjuvant radiotherapy
or adjuvant chemotherapy is ~ 3-4%.
The most common sites of relapse are PAN (88%), mediastinal or pelvic LNs (6%) and ipsilateral
inguinal nodes (6%).
Risk factors for an increased risk of relapse are tumours >6cm, age <35, vascular or lymphatic
invasion or rete testis involvement. The relapse rate for patients without invasion is ~ 9.5%, with
vascular or lymphatic invasion ~ 17% and for vascular and lymphatic invasion ~ 37%.
Supranetwork Treatment Recommendations for stage I seminoma
[2G-329,]
At present the current standard treatments recommended by EGCCCG for stage I seminoma are
the individualized informed choice of surveillance, adjuvant chemotherapy or adjuvant
radiotherapy.
Patients electing to have outpatient radiotherapy or chemotherapy treat should be able choose
and pre-book this treatment. However patients must receive commence their treatment within 50
days of orchidectomy.
The treatment, surveillance and follow-up protocols for the management of stage I seminoma are
given in;
Stage I seminoma Adjuvant Radiotherapy
Stage I seminoma Surveillance Protocol
Stage I seminoma Follow-up after adjuvant therapy
Stage I seminoma Adjuvant chemotherapy
(Appendix 23.1)
(Appendix 23.2)
(Appendix 23.3)
(Appendix 23.4)
Supranetwork Policy Management of Stage I Germ Cell Tumours of the Testis
Stage 1 NSGCT
Natural History
Approximately 60% of NSGCT make AFP and/or hCG tumour markers that can be helpful monitor
the disease. The overall risk of relapse in stage I NSGCT is 25-30 %. Of those who do relapse,
80% do so by 1 year and > 90% before 2 years. The most common sites of relapse are the PAN
50%, the lungs or mediastinum 32 % and marker only relapse in12%.
Prognostic factors
The simplest prognostic factors are the presence of venous and/or lymphatic invasion in the
primary tumour. Patients with these risk factors have a 38% risk of relapse whilst those without
have a 15% risk.
Supranetwork Treatment Recommendations for stage I NSGCT
126
The most common current treatment of stage I NSGCT is surveillance followed by combination
chemotherapy for those who relapse. The Supranetwork Surveillance protocols for marker
negative and marker positive NSGCT are listed in Appendix 23.2 and Appendix 23.4.
An alternative for those at the higher risks of relapse is adjuvant chemotherapy with 2 cycles of
BEP. This has been shown to reduce the relapse rate of high risk patients from 40% to 1-2%.
The potential benefits of adjuvant chemotherapy for high risk patients can be discussed with these
patients. However clinician and patients should be reminded that this approach involves 60% of
patients receiving 2 cycles of BEP chemotherapy unnecessarily.
It should also be noted it is unusual for stage I patients in a surveillance programme to present
with disease apart from in the good prognosis group.
Supranetwork Policy Management of Stage I Germ Cell Tumours of the Testis
Stage I mixed Seminoma/NSGCT
Natural History
These mixed tumours make up ~ 15% of stage I patients. Despite the presence of mixed histology
these tumours behave in a manner almost identical to Stage I NSGCT with the majority of those
who relapse doing so within the first year (74% within year 1, 12% within years 1-2 and 14% in
years 2-5).
Supranetwork Treatment Recommendations for Stage I Mixed GCT
The recommendations from COIN and other authors are to manage as for stage I NSGCT.
14.0
Supranetwork MDT Policies for The Management of Advanced Germ Cell Tumours of
the Testis
Overview
The management of advanced testicular GCT is predominantly with the use of cisplatin based
chemotherapy.
To ensure adequate management and avoid over-treatment, patients should be staged and their
prognostic grouping worked out using the IGCCCG standards as shown below.
Advanced Disease Pre-treatment Investigations
CT Thorax Abdomen Pelvis
MRI Brain
GFR
Tumour markers LDH, AFP, bHCG
Sperm storage (see Appendix 24.2 and Appendix 24.3)
Pulmonary Function Tests
Patients with risk factors for bleomycin pulmonary toxicity, such as previous radiotherapy,
smokers, age over 40 or poor renal function should have lung function including VC and Kco as
agreed locally
A checklist, treatment guide and summary of the IGCCCG groups is provided on form (Appendix
24.1) which should be completed and filed in the patients notes prior to starting chemotherapy.
IGCCCG Prognostic Groups and Historical Cure Rates
Teratoma (NSGCT)
Seminoma
Good prognosis with all of:
127
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
AFP<1000 ng/ml
HCG<5000 iu/l
LDH<1.5 upper limit of normal
56% of teratomas
5-year survival 92%
Any primary site
No non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
90% of seminomas
5-year survival 86%
Intermediate prognosis with all of:
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
28% of teratomas
5-year survival 80%
Any primary site
Non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
10% of seminomas
5-year survival 73%
Poor prognosis with any of:
Mediastinal primary or non-pulmonary
visceral metastases
AFP>10,000 ng/ml or
HCG>50,000 iu/l or
LDH>10 normal
16% of teratomas
5-year survival 48%
No patients classified as poor prognosis
Advanced Testicular Cancer Management by Stage and Prognostic Grouping
Seminoma Stage IIA/IIB
The historical treatment of stage IIA/B seminoma has been radiotherapy using 30-36Gy.
However more recently chemotherapy has been increasingly used in this situation, particularly in
patients with bulky disease or those not wishing to have RT.
There is some interest in using radiotherapy combined with chemotherapy, but this is not yet
regarded as a routine treatment.
Supranetwork Treatment Recommendations for Stage IIA/IIB seminoma
Whilst radiotherapy remains a standard treatment option in this situation, the clinicians within the
Supranetwork group mainly treat these patients with chemotherapy.
The standard chemotherapy protocols are;
BEP x 3
EP x 4
For individual patients preferring to have radiotherapy or unsuitable for chemotherapy the
Supranetwork RT protocol for stage IIA/IIB seminoma (Appendix 24.4)
In these patients who need chemotherapy treatment but where BEP based therapy is clinically
contraindicated, treatment with Carboplatin AUC 10 (x3-4) can be an alternative.
Advanced Testicular Cancer Management by Stage and Prognostic Grouping
Seminoma Stage IIc/III/IV
128
Treatment of advanced seminoma is associated with high cure rates. Previous studies have
confirmed the superiority of cisplatin based combination chemotherapy over single agent
carboplatin.
Supranetwork Treatment Recommendations for Advanced Seminoma Stage IIc/III/IV
Following the current opinions and data the treatment options could include;
BEP x 3 or EP x 4 for good prognosis disease.
In these patients who need chemotherapy treatment but where BEP based therapy is clinically
contraindicated, treatment with Carboplatin AUC 10 (x3-4) can be an alternative
For the Seminoma patients with disease that falls into the IGCCCG intermediate prognosis
disease treatment should be with BEP x 4 or POMB/ACE.
The details of the Supranetwork standard chemotherapy regimens are found in Appendix 24.5.
Notes on Bleomycin administration in advanced seminoma
At present there is no clear data on the importance of the use of Bleomycin in chemotherapy for
advanced seminoma. Whilst most clinicians and guidelines support the use of standard Bleomycin
containing regimens in advanced seminoma, the omission of Bleomycin in cases were toxicity
risks are enhanced should be considered with a lower threshold than in advanced NSGCT.
Patients particularly at risk of Bleomycin pulmonary toxicity include those with; previous
radiotherapy, poor lung function, >40 years, GFR <80ml/min, stage IV disease at presentation.
If the risks/benefits of Bleomycin use in a patient with seminoma are felt to favour omission then
the use of EP for 4 cycles is indicated.
Advanced Testicular Cancer Management by Stage and Prognostic Grouping
Management of Advanced NSGCT
NSGCT is a chemosensitive disease and high cure rates can be obtained in all disease stages
and prognostic groups
IGCCCG Good Prognosis group
This group carries a cure rate of 92% at 5 years. Recent research has focused on the reduction of
treatment related morbidity and mortality. There has been encouraging data to support that 3
cycles of BEP are equivalent in efficacy to 4 cycles from a study in the USA and this has been
supported by the results of an MRC/EORTC study.
Supranetwork Treatment Recommendations for Good Prognosis NSGCT
In keeping with the current COIN and EGCCCG recommendations for good prognosis NSGCT the
recommendation of the Supranetwork is treatment with 3 cycles of BEP.
Notes on chemotherapy in advanced NSGCT
Reduction of toxicity
Carboplatin vs Cisplatin
Cisplatin is associated with significant toxicity, however studies that have substituted Carboplatin
for Cisplatin demonstrated inferior response rates and relapse free survival. As a result Cisplatin
remains the drug of choice.
Removal of Bleomycin
129
Bleomycin is associated with potentially severe or fatal toxicity such as pneumonitis and
pulmonary fibrosis which can occur in up to 2-3% of patients. However studies that have looked at
removing Bleomycin have resulted in significantly reduced survival in the patients not receiving
Bleomycin.
The COIN and EGCCCG guidelines currently recommend that Bleomycin is retained in the
treatment of good prognosis NSGCT with the dosage limited to a total of 270mg.
In patients who have significant risk factors for lung disease or show signs of early Bleomycin
toxicity 4 cycles of EP are a suitable alternative
Advanced Testicular Cancer Management by Stage and Prognostic Grouping
Management of Patients with Intermediate and Poor Prognosis NSGCT
The prognosis for these patients is less good with historical 5-year disease free survival rates of
40-80 %. The main aim of therapeutic research has been to develop treatments with improved
efficacy that have acceptable toxicity. Investigations looking at either more complex drug regimens
(BOP/VIP, VIP) or increasing the doses of the drugs in BEP (Cisplatin x 2 dose) have not in
randomised trials proved to be superior in terms of survival than BEP and are frequently more
toxic.
A number of other protocols including POMB/ACE and C-BOP-BEP have in phase II trials
demonstrated improved survival over historical controls, however these have not been subject to a
comparative phase III trial with BEP.
Of note a number of recent results indicate that the current modern survival figures for patient with
poor/intermediate prognosis GCT are significantly improved on the historical figures above.
Treatment Options
The current COIN and EGCCCG recommendations for intermediate and poor prognosis NSGCT is
4 cycles of BEP with a total Bleomycin dose of 360mg (12 x 30mg)
An alternate treatment developed at Charing Cross hospital has been in use there for many years
at and also at Mount Vernon Hospital.
The POMB-ACE protocol gives results comparable to and potentially superior to BEP when judged
by historical controls, however to date there have not been any randomised trials to formally
examine the superiority or equivalence of these regimens.
Within the Supranetwork there is considerable experience with POMB-ACE and so both BEP x4
and POMB-ACE (7) are treatment options in intermediate and poor prognosis NSGCT.
Supranetwork Treatment Recommendations for Intermediate Prognosis NSGCT
In keeping with the current COIN and EGCCCG recommendations for intermediate prognosis
NSGCT the recommendation of the Supranetwork is treatment with 4 cycles of BEP.
Alongside this the Supranetwork also supports the use of POMB-ACE (7) chemotherapy for these
patients
Supranetwork Treatment Recommendations for Poor Prognosis NSGCT
In keeping with the current COIN and EGCCCG recommendations for intermediate prognosis
NSGCT the recommendation of the Supranetwork is treatment with 4 cycles of BEP.
Alongside this the Supranetwork also supports the use of POMB-ACE (7) chemotherapy for these
patients.
Supranetwork Follow-up recommendations for follow-up after chemotherapy for advanced
Testicular GCT
130
The standard follow up protocols for patients treated for advanced GCT are found in Appendix
24.6. The protocols document the frequency of clinical review, tumour marker measurement and
imaging investigations. Additionally the protocol contains measures to identify patients with
treatment related hypertension.
Follow up Guidelines (08-2G-313 )
Written follow up guidelines are agreed between the Supranetwork team and the referring team(s)
and endorsed by the NSSG.
.
Operations to resect residual masses post-chemotherapy
for the team's patients (08-3G-314)
Mr Hrouda and Mr Khoubehi are the RPLND surgeons and core members of the Testicular
Supranetwork MDT.
Advanced Testicular Cancer Management by Stage and Prognostic Grouping
Special considerations
Patient Support
Many patients find the sharing of the experience of treatment with one of our previous
chemotherapy patients extremely valuable. To support this approach a number of our ‘Old Boys’
have volunteered to be a ‘buddy’ to new patient if required and are happy to meet with or speak
over the phone to our new chemotherapy patients.
Brain metastases
Approximately 10% of all patients with advanced germ cell tumour present with brain metastases
(i.e. 1-2% of all patients with testicular tumours).
Patients who present with brain metastases at initial diagnosis have a long-term survival of ~ 3040%, whereas those who develop metastases during first-line treatment or in the context of
recurrent disease outside the brain have a 5-year survival of only 2-5%.
The presence of choriocarcinoma indicates a poor prognosis independent from any form of
treatment.
The treatment is with curative intent. The optimal sequence of the treatment modalities of
chemotherapy, radiotherapy and neurosurgery is not yet fully defined. In a multivariate analysis
cranial irradiation in addition to chemotherapy improved the overall prognosis of patients who
present with a brain metastasis. It has not yet been defined whether consolidating irradiation of the
CNS is required after complete remission has been achieved by chemotherapy alone.
Supranetwork Treatment Recommendations for Treatment of patients with brain
metastases
Alternating high dose EP/OMB (high dose methotrexate) chemotherapy
Intrathecal methotrexate should be given with each cycle of EP.
Consider Surgery and Radiotherapy
Palliative Care
Whilst overall the large majority of patients with testicular cancer will be cured of their disease, the
cure rate is still short of 100%. In the patients who are not going to be cured of their illness, it is
131
important to involve the palliative care team appropriately. The assistance of the palliative care
team in the management of distressing symptoms, arranging hospice care and the support for
families, often including young children is essential in optimising care.
15.0
Supranetwork MDT policies on the management of relapsed Testicular Cancer
In relapse following first-line treatment, the localisation and histology of the primary tumour, the
response to first-line treatment, the duration of previous remissions, as well as the level of the
tumour markers AFP and HCG at the time of relapse or progression are known prognostic
indicators. Relapse management is therefore dependent upon previous to therapy, time to relapse
and site of the relapse.
Data suggests that relapses frequently (76%) occur at single sites with the most frequent sites
being the retroperitoneum (48%), the mediastinum (32%) the pelvis (12%), the liver (12%) and the
lungs (8%). Additionally isolated relapses can also occur in the testis and the brain
Prior to institution of second line treatment, further investigations particularly in marker negative
patients is warranted as other diagnoses such as growing mature teratoma, sarcoidosis, thymic
hyperplasia and a second malignancy can mimic the pattern of a late relapse of GCT
Seminoma
Relapse after adjuvant therapy for stage I
The majority of patients who relapse after first-line radiotherapy or adjuvant carboplatin have a
cure rate of >90% and should receive standard cisplatin-based chemotherapy as in the treatment
plan for advanced seminoma.
Relapse after 1st line chemotherapy
Conventional dose cisplatin-based salvage chemotherapy after first-line therapy with BEP will
result in long-term remissions of 20~50% of patients. The regimens of choice are 4 cycles of VIP,
TIP, or VeIP.
NSGCT
Relapse after 1st line chemotherapy
Salvage chemotherapy after first-line chemotherapy for metastatic disease consists of 4 cycles of
VIP, TIP, or VeIP. Conventional dose cisplatin-based salvage chemotherapy can achieve longterm remission in 15-40% of patients depending upon individual risk factors.
High dose therapy and PBSCT at Hammersmith Hospital
A relatively small number of patients are not cured by first line chemotherapy and require further
treatment. Generally the recommendation for these patients is to have second line chemotherapy
using TIP, VIP or another suitable regimen.
Alongside this a number of centres have explored the use of high dose chemotherapy with
PBSCT.
Whilst encouraging results have been obtained, patient numbers have been small and phase III
trials have been of too small a size to make clear conclusions about the absolute value of the
procedure.
With the long experience of the Supranetwork in high dose chemotherapy for relapsed germ cell
tumours, this is a procedure that we continue to support for the Supranetwork’s own patients and
for those referred in from outside.
Supranetwork Treatment Recommendations for High Dose Chemotherapy and PBSCT
Selected patients with relapsed germ cell tumours may be offered treatment with high dose
chemotherapy with PBSCT.
The role of high dose chemotherapy in a patient’s care must be discussed at the Supranetwork
MDT. Patients for whom high dose chemotherapy is indicated should be referred to Dr Ed Kanfer
at the Haematology Departments Transplant Unit at Hammersmith Hospital.
132
The stem cell harvest is arranged at Charing Cross Hospital, the work up for high dose and the
procedure are performed at Hammersmith Hospital under the care of the haematology team.
Special Consideration
Late relapse of Testicular Germ Cell Tumours
Late relapses occurring > 2 years after chemotherapy are rare, with the risk estimated at 1.1% at 5
years and 4% at 10 years.
Management of late relapses
The treatment of choice for isolated late relapses is surgical excision. The role of post surgery
chemotherapy is unclear for these patients. For patients with inoperable late relapses the
prognosis is poor and the responses to chemotherapy relatively disappointing.
Palliative Care
Whilst overall the large majority of patients with testicular cancer will be cured of their disease, the
cure rate is still short of 100%. In the patients who are not going to be cured of their illness, it is
important to involve the palliative care team appropriately. The assistance of the palliative care
team in the management of distressing symptoms, arranging hospice care and the support for
families, often including young children is essential in optimising care.
16.0
Retroperitoneal Lymph node dissection (RPLND) in Testicular Cancer
Residual masses after chemotherapy for advanced testicular cancer a frequent occurrence.
Studies demonstrate that approximately 50% of masses contain fibrosis/necrosis, 35% contain
mature/differentiated teratoma but 15% contain active malignancy. In attempts to minimise the
numbers of patients undergoing the procedure a number of prognostic models have been
examined. However these models have not proved to be of sufficient accuracy to use in routine
practice.
Pending the development of superior prognostic systems or secure data from other modalities
such as PET scanning the Supranetwork works to the old established size and pathology based
criteria
Supranetwork
chemotherapy
Treatment
Recommendations
for
consideration
of
RPLND
after
Seminoma
Post-chemotherapy as well as post-radiotherapy residual masses in seminoma patients are
common and irrespective of the size should not necessarily be resected.
However, the patient should be closely followed by imaging investigations and tumour marker
evaluations. There is emerging data that PET scans may be helpful in indication the presence of
potentially viable residual tumour in this situation and consideration should be given to routine PET
scan in these patients.
NSGCT
The risk-benefit ratio of surgery is a function of mass size. The cut-off has yet to be defined.
Patients who achieve complete remission, i.e. negative tumour markers and residual masses
<1cm after chemotherapy, post-chemotherapy RPNLD is not required.
For those patients with a residual mass >1cm and normalisation of tumour markers the residual
masses should be resected.
Consider for resection of post-chemotherapy residual tumour masses in patients whose tumour
markers have not normalised (evidence of drug resistance) should be made particularly when
surgery should conceivably remove all sites of disease.
133
Supranetwork Treatment Recommendations for patients with multiple sites of residual
mass
For patients with residual tumour masses at multiple sites such as the PAN and lungs, an
individual decision should be made by the Supranetwork MDT regarding the number and
extension of resections.
Supranetwork MDT and RPLND Surgical Location and Personnel
Due to the high treatment related acute morbidity, surgery of residual masses should be performed
only at specialist centres.
All patients with residual post-chemotherapy masses, or metastatic disease that has relapsed
more than two years following chemotherapy should be discussed at the Supranetwork MDT.
RPLND surgery is performed by Mr Hrouda or Mr Koubehi.
A summary of the cases treated with RPLND will be produced for the Supranetwork annually.
17.0
Trials, Research,
334/335/336/337)
Audit and Datasets by the Supranetwork MDT
(08-3G-
It is the policy of the Supranetwork to participate in research and audit as fully as possible.
The Supranetwork will be aiming to support local and national clinical trials as appropriate.
The Supranetwork is currently supporting the trials;
Cancer Research Network (08-2G-336/ 08-2G-337)
The MDT should produce a written response annually to the NSSG's approved list of trials and
other well designed studies, which fulfils the following:
 For each clinical trial and other well designed study the MDT should agree to enter patients
or state the reason why it will not be able to;
 The remedial action arising from the MDT's recruitment results, agreed with the NSSG. (see
Appendix 17& 18 – List of NSSG Trials and Remedial Action Proforma)
Network and Local Audits (08-2G- 334/08-2G-335)
The Supranetwork will perform the routine audits as required by the Standards.
These audits will be performed annually and will include
1. An audit of new patients diagnosed within the Supranetwork area. This audit will examine;
I) The pattern of referral of high risk cases pre/or post orchidectomy
II) Referral of all cases within the 24 hour target
III) Referral according to Network Guidelines
IV) Treatment according to Network Guidelines
The interval from diagnosis to the patients GP being informed by the end of the
following working day after the patient is given a diagnosis of cancer.
2. The Supranetwork will produce an annual survey of the patient’s experience of the services
offered by the Supranetwork MDT ( 08-3G-323 / 08-3G-324)





The survey will include the following questions as a minimum
If the patient was offered a key worker
The provision of information for patients/carers
The offering of an opportunity for a permanent record of consultation
Further question can be added as wished by the MDT
(Appendix 12 - Patient Survey 2010)
134
3. Additionally the Supranetwork will perform with the agreement of the NSSG a separate
audit each year on a topic of interest. The Results are presented to the Supranetwork
MDT (08-2G- 334/08-2G-335)
(Appendix 3 – Minutes of the Testicular Supranetwork MDT Annual Meeting)
(Appendix 13- Network Agreed Audit).
.
Patient Journey Mapping Procedure
The Supranetwork will carry out a mapping exercise examining the patient journey.
The key points will be from each stage to the next in the patient journey and the data will report on
waiting times and any steps to be taken to improve them.
Datasets
The Supranetwork will collect data based on the BAUS Dataset of;











Date of GP referral
Date of histological diagnosis
Definition of histological diagnosis
Stage of disease
Prognostic category
Contralateral biopsy
Treatment plan
Response
Relapse
Cause of death
Additionally the Supranetwork will also collect data on;
- Cancer Waiting times
Data Results 2009/10
For Annual Testicular referrals (08-2G-338) and the total annual number of post chemotherapy
surgical resections by individual surgeon (08-2G-338), please refer to the West London
Testicular Supranetwork Annual Report 2009/10, Section 3.0- Supranetwork activity)
Cancer Minimum Data Set (08-3G-332)
The MDT has agreed the same minimum dataset (MDS) with other MDTs of the same cancer
site(s) across the North West London Cancer Network. (See Urology NSSG Constitution 2010 –
p.5) The MDS should include the data items required for:

The cancer waiting times monitoring, including Going Further on Cancer Waits in
accordance with DSCN 20/2008, to the specified timetable as

specified in the National Contract for Acute Services;

The Cancer Registration Dataset as specified in the National Contract for Acute
Services.
(Appendix 15- NWLCN Cancer Minimum Dataset)
The Electronic Collection of MDS (08-3G-333)
The MDT has agreed the same methodology of collecting the minimum dataset (MDS) with other
MDTs of the same cancer site(s) across the network (network-wide MDS). (See Urology NSSG
Constitution 2010 – p.5) The Thames Cancer Registry Minimum Data Set requirement for the
MDT is a phased approach.


Pathology and Cancer waiting times are already being collected.
The MDT co-ordinator records the cancer waiting times section of the MDS which is
electronically retrievable.
135

18.0
.The MDT now collects staging and co-morbidity via the MDT Patient Summary.
(Appendix 5 – MDT Discussion Proforma) (NB: Agreed NSSG MDS Policy is outlined
in the WLCN Constitution)
DoH Recommendations not addressed by the Supranetwork MDT document
It is the aim of the Supranetwork that any patients referred with a potential diagnosis of testicular
cancer are seen in the next clinic. This approach should be more timely and more secure than a
patient choice system. (08- 2G-359)
It is the aim of the Supranetwork that initial diagnostic tests are performed as a matter of urgency.
A pre-book system would potentially be at odds with this. (08- 2G-360)
It is the aim of the Supranetwork that patient’s first treatment whether this orchidectomy or
chemotherapy should be at the earliest possible time. A pre-book system is at odds with this.
(08-2G-361)
136
Appendix 19- Urology Summary
North West London Supranetwork Testicular Cancer MDT
Overview of Urology Investigation and Management Protocols
(Please see the NWLCN Supranetwork Testicular Cancer
Urology Clinic Folder for more details)
1/ Patients referred with a potential diagnosis of testicular cancer should be seen in the next clinic of any of
the urology consultants.
2/ Pre-operative investigations include US of the testes, CXR and tumour markers (LDH, AFP and bHCG)
3/ The details of routine patients proceeding to orchidectomy should be faxed using the proforma to either
Charing Cross (Dr Savage, Prof Seckl), Chelsea and Westminster (Dr Brock) or Mount Vernon (Prof Rustin)
before or on the day of surgery. Do not wait for the path report or the removal of stitches!
4/ The local clinical nurse specialist and the Supranetwork MDT co-ordinator must also be informed
Edward Marshall
Tel 0208 846 1674
Fax 0208 846 1757.
5/ The patient will be registered at Charing Cross, Chelsea and Westminster or Mount Vernon and the CT
scans and other staging investigations organised by the Oncology teams at those hospitals
6/ The Oncology Centre will confirm the date/time of the first out-patients appointment at Charing Cross,
Chelsea and Westminster or Mount Vernon on the same day as receiving the fax/phonecall.
7/ Please confirm the Oncology clinic arrangements with the patient before discharge
Advanced Testicular Cancer Can Be An Emergency
Important note re High Risk Patients
Some testicular cancer patients present with advanced disease that can rapidly be life threatening. These
patients must be discussed with the oncology team at either CXH or Mount Vernon prior to considering
orchidectomy. Many of these patients need urgent chemotherapy, without any delays/risks from surgery and
the risk of wound infections etc.
Emergency High Risk contacts
Charing Cross
0208-846-1234 on call Med Onc SpR
Chelsea and Westminster
0208-846-1234 on call Med Onc SpR
Mount Vernon
0845 241 1299 on call Med Onc SpR
In case of any contact difficulties with the above contacts;
Dr Savage at CXH 078-244-99125
137
Appendix 20 – Urology Checklist
West London Testicular Cancer Supranetwork MDT
Investigation Proforma to be filed in the Urology Notes
Patient Details
Surgical Assessment Proforma/Notes Check List for Routine Orchidectomy Patients
The majority of patients with testicular cancer present with an obvious mass and no other
symptoms should have a limited number of initial investigations and then proceed to orchidectomy
and Oncology referral.
Important Note re High Risk Patients
A few patients present with evidence of advanced disease such as; high markers, an abdominal
mass, lung mets or CNS symptoms. This group of patients must be discussed with the oncology
team prior to consideration of orchidectomy.
For the routine patients the following investigations should be performed pre-operatively;
Pre-Operative Investigations
Date
Result
Testicular Ultrasound
Chest X Ray
AFP
bHCG
LDH
Please indicate if a fitting prosthesis was discussed pre-operatively Yes
No
Post-Operative Investigations
Date
Result
AFP
bHCG
LDH
138
Appendix 21.1 – Oncology Referral Letter
West London Supranetwork Testicular Cancer MDT
Oncology Referral Pro-Forma
Patient details
GP details
Date
Dear Oncology Team,
Please could you arrange to see this man with testicular cancer in your clinic. The orchidectomy
date is ______
The patients urology care has been under the care of Mr/Mrs ______________________ at
___________________________ Hospital.
The results of his pre-operative investigations were
Date
Result
Testicular Ultrasound
Chest X Ray
AFP
bHCG
LDH
Please indicate if a fitting prosthesis was discussed pre-operatively.
Yes
No
A formal referral letter will follow shortly.
Please contact the patient via:
Home phone
Mobile phone
In patient on
__________________
__________________
__________________
Yours sincerely
Bleep #
Please fax and post to one of;
Charing Cross (0208-383-5577 Dr Savage and Prof Seckl)
Chelsea and W (0207-846-8863 Dr Brock )
Mount Vernon (01923-844840 Prof Rustin)
139
Appendix 21.2 – Pathology Request letter
West London Supranetwork Testicular Cancer MDT
Pathology Request Letter
Patient details
Date
Dear Dr
This patient has recently been referred to _________ Hospital with a provisional
diagnosis of testicular cancer following an orchidectomy performed on _________,
under the care of _______________.
It is the policy of the Supranetwork Testicular Cancer MDT to arrange a central
review of the pathology of these patients at the earliest opportunity.
We would be grateful if you could forward representative slides and blocks to allow
this.
Please send the samples to;
The GTT centre
Department of Medical Oncology
Charing Cross Hospital
Fulham Palace Rd
London
W6 8RF
Tel 0208-846-1409
Yours sincerely
Dr Savage/Prof Seckl
Consultant in Medical Oncology
Charing Cross Hospital
140
Appendix 22.0 – Oncology Checklist
West London Supranetwork Testicular Cancer MDT
Initial Oncology Assessment Checklist
The following should be arranged at the patient’s initial visit to the Oncology Treatment Centre.
Investigations
CT Scan Thorax Abdomen and Pelvis
Full blood count
Biochemistry
Tumour markers AFP, hCG, LDH
CXR
Documentation
Please document the following
1/ Pathology review already requested
Yes
No
If No Pathology review requested today Yes
2/ Has Key Worker been identified
Yes
No
If Yes Who is it
3/ Has the Supranetwork Testicular MDT information on testicular cancer been given?
Yes
No
4/ Has a permanent record of the discussion regarding treatment options been offered?
Yes
No
141
Appendix 23.1 - Stage 1 Seminoma RT Protocol
West London Testicular Cancer Supranetwork MDT
Standard Radiotherapy Treatment
Stage I seminoma
The target volume of irradiation includes the infradiaphragmatic para-aortic / paracaval lymphatics.
The upper and lower fields are defined by the upper edge of T11 and the lower edge of L5.
Ipsilateral to the primary tumour the lateral field margin should be extended to the renal hilum; the
contralateral margin has to include the processus transversus of the lumbar vertebrae. The total dose
is 20Gy, applied in single dose of 2Gy each, five fractions per week. (Jones et al, J Clin Oncol.
2005; 23(6): 1200).
The use of a linear accelerator is mandatory.
If previous inguinal / scrotal surgery, the field may be extended to a ‘dogleg’ radiotherapy (to
include ipsilateral iliac and inguinal LN), 30Gy in 15 fractions [ESMO guidelines]. Some groups
feel this may not be indicated in that there is no evidence for a different clinical outcome [EGCCG
guidelines].
Limited target volume and doses of modern adjuvant radiotherapy further reduce treatment-related
side-effects such as impairment of fertility due to scatter of radiation to the remaining testicle.
Therefore radiation effects on the patient’s spermatogenesis due to scatter doses, which is always
<2Gy, seem to be unlikely and do not require shielding of the contralateral testis.
142
Appendix 23.2 – Stage I Seminoma Surveillance Protocol
North West London Testicular Cancer Supranetwork
STAGE I SEMINOMA –Ten Year Surveillance Protocol
Pre-op
AFP
Orchidectomy
Date:
Pre-op
hCG
Pre-op
LDH
At each attendance check neck and abdominal lymph nodes, nipples, contralateral testis and ask about back
ache and if patient is performing testicular self examination
Appointment
schedule
Baseline
Date
Next
appointment
1 month
CT
CXR
AFP
hCG





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




Late
effects
TAP
1 month
3 months
6 months
9 months
1 Year
15 months
18 months
21 months
2 Years
28 months
32 months
3 Years
3.5 Years
4 Years
4.5 Years
5 Years
6 Years
7 Years
8 Years
9 Years
10 Years
2 months
3 months
3 months
3 months
3 months
3 months
3 months
3 months
4 months
4 months
4 months
6 months
6 months
6 months
6 months
1 year
1 year
1 year
1 year
1 year
1 year
Abdo
Abdo
Abdo
Abdo



Notes
1/ CT scan of Chest Abdomen and Pelvis at initial staging
2/ CTs subsequently are routinely of the abdomen only unless clinically indicated pelvis at high risk.
3/ In seminoma Tumour Markers should be checked just at the clinic visits
143
Appendix 23.3 – Stage I Seminoma Follow up after Adjuvant Treatment
North West London Testicular Cancer Supranetwork MDT
Stage I seminoma follow-up after adjuvant chemotherapy or
radiotherapy
Clinic visits
Year 1
Year 2-5
Year 6 onwards
3 monthly clinic visits
6 monthly clinic visits
annual visits
Imaging
1/ CT scan of Thorax and Abdomen should be performed at 18-24 months
2/ CXR should be performed at alternate visits and stopped at the end of
year 3
Tumour Markers
Follow-up post adjuvant therapy for stage I seminoma
Serum AFP, hCG and LDH at clinic visits only
Late Effects
Investigations at Years 2, 5 and 10
Blood pressure, height and weight,
Urea and creatinine, fasting cholesterol (HDL and LDL) triglycerides,
fasting glucose, FSH, LH and testosterone
144
Appendix 23.4 – Stage 1 NSGCT – Surveillance Protocol
STAGE I NSGCT –Ten Year Surveillance Protocol
Pre-op
Pre-op
Pre-op
AFP
hCG
LDH
At each attendance check neck and abdominal lymph nodes, nipples, contralateral testis and ask about
back aches and if patient performing testicular self examination
Orchidectomy
Date:
Appointment
schedule
Baseline
1 month
2 months
3 months
Date
Next
appointment
1 month
1 month
1 month
1 month
CT
CXR
AFP
hCG
TAP











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











Late
effects
Abdo
4 months
5 months
6 months
7 months
8 months
9 months
10 months
11 months
1 Year
1 month
1 month
1 month
1 month
1 month
1 month
1 month
1 month
2 months
Abdo
14 months
16 months
18 months
20months
22 months
2 Years
27 months
30 months
33 months
3 Years
40 months
44 months
4 Years
4.5 Years
5 Years
5.5 Years
6 Years
7 Years
8 Years
9 Years
10 Years
2 months
2 months
2 months
2 months
2 months
3 months
3 months
3 months
3 months
4 months
4 months
4 months
6 months
6 months
6 months
6 months
1 year
1 year
1 year
1 year
Discharge



Notes
1/ CT scan of Chest Abdomen and Pelvis at initial staging
2/ CTs subsequently are routinely of the abdomen only unless clinically indicated pelvis at high risk
3/ In NSGCT Tumour Markers should be checked every 2 weeks for the first 3 months and then
subsequently just at the clinic visits
145
Appendix 24.1
Staging IGCCCG prognostic groups and Recommended treatments
West London Supranetwork MDT Testicular Cancer Treatment Plan
Name
Pathology
DoB
IGCCCG Group
Consultant
IGCCCG Prognostic grouping
Treatment Plan
Teratoma (NSGCT)
Seminoma
Good prognosis with all of:
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
AFP<1000 ng/ml
HCG<5000 iu/l
LDH<1.5 upper limit of normal
56% of teratomas
5-year survival 92%
Any primary site
No non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
90% of seminomas
5-year survival 86%
Intermediate prognosis with all of:
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
AFP1000 and10000 ng/ml
or HCG 5000 and  50000 iu/l or
LDH  1.5 normal  10 normal
28% of teratomas
5-year survival 80%
Any primary site
Non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
10% of seminomas
5-year survival 73%
Poor prognosis with any of:
Mediastinal primary or non-pulmonary visceral
metastases
AFP>10,000 ng/ml or
HCG>50,000 iu/l or
LDH>10 normal
16% of teratomas
5-year survival 48%
No patients classified as poor prognosis
MDT treatment options by IGCCC Prognostic group
Good Prognosis
BEP x 3 or
EP x 4
Intermediate Prognosis
BEP x 4 or POMB/ACE (5)
Poor Prognosis
POMB/ACE (7) or BEP 4
Poor prognosis with cerebral Mets at presentation
EP/OMB plus IT MTX
Pre-treatment investigations for cycle 1
CT TAP
MRI brain
GFR and repeat prior to cycle 3
Sperm storage if time permits
Respiratory function tests and repeat prior to cycle 3
Aim to avoid routine anti-emetic steroids
146
Appendix 24.2
Sperm storage Information
West London Supranetwork Testicular Cancer MDT
Sperm storage
Supranetwork Policy on Sperm Storage
All patients should be offered sperm storage. The only exceptions to this are patients who need
urgent chemotherapy.
It is the policy of the Supranetwork that the outcomes of discussions and decisions about sperm
storage are included in the patients case notes.
Sperm storage cryopreservation is performed via the Andrology laboratory, Hammersmith Hospital
– Dr Kevin Lindsay, Principal Clinical Scientist in Andrology.
Contact details
0208 383-4680
Tel Fax
0208 383-3591
For patients proceeding to sperm storage HIV and Hep B&C status must be checked.
However the patient can proceed with sperm storage whilst the virology tests are being processed.
N.B. A standard referral letter is attached in the Appendix. 24.3 – Sperm Storage Request
Letter
147
Appendix 24.3
Sperm storage request letter
Date
Re
Dear Andrology Unit,
Thank you very much for arranging sperm storage for this man. He has recently been diagnosed
with testicular cancer and is keen to arrange sperm storage. We have already taken blood serology
for Hep B, Hep C and HIV and await the results.
Thank you for your help
Yours sincerely
Philip Savage/Michael Seckl
Consultant in Medical Oncology
Charing Cross Hospital
London
W6 8RF
Tel 0208-846-1419/1421
Fax 0208-748-5665
The sperm storage facility is at the Andrology Laboratory at the Hammersmith Hospital. The
service is available between 9-12 Mondays to Fridays and no appointment is necessary.
The Hammersmith Hospital is in Du Cane Rd in East Acton, it is relatively close to both East
Acton and White City Tube stations. There is also pay and display parking available on site.
To allow sperm to be saved long term you will need to be tested for HIV and Hepatitis, this will be
done routinely in the Oncology clinic. If you have any concerns or issues regarding these tests,
please discuss then with your consultant.
148
Appendix 24.4
Stage IIA Seminoma RT
West London Testicular Cancer Supranetwork MDT
Standard Treatment Protocol
Stage IIA-IIB disease:
Radiotherapy to para aortic nodes (+/- dogleg) 30Gy in 15 # with 5Gy boost at involved site
149
Appendix 24.5
1st line Chemotherapy regimens
West London Testicular Cancer Supranetwork MDT
Standard Drug Regimens for 1st line use
Carboplatin
AUC 7 (EDTA measured clearance)
BEP 5 day
Given over
Cisplatin
Etoposide
Bleomycin
5 Days
20mg/m2
100mg/m2
30mg
3 weekly cycle
D1-5
D1-5
D1, 8, 15
EP 5 day
Given over
Cisplatin
Etoposide
5 Days
20mg/m2
100mg/m2
3 weekly cycle
D1-5
D1-5
West London Supranetwork Testicular Cancer Team
Standard Drug Regimens
POMB/ACE
POMB
D1
Vincristine 1mg/ m2 iv bolus
Methotrexate 100mg/ m2 iv bolus
and then 200mg/ m2 iv for 12 hours
D2
Bleomycin 30mg by 24 hour iv infusion
Folinic acid 15mg po 6 hourly x 4 given at 24,36,48 and 60hrs post MTX.
D3-4
Cisplatin 40mg/ m2 with hydration
Cisplatin 40mg/ m2 with hydration
Cisplatin 40mg/ m2 with hydration
ACE
D1
Etoposide 100mg/ m2
Actinomycin D 0.5mg
150
D2
Etoposide 100mg/ m2
Actinomycin D 0.5mg
D3
Etoposide 100mg/ m2
Actinomycin D 0.5mg
Cyclophosphamide 500mg/m2
Treatment interval 2 weeks
Treatment sequence P-P-A-P-A- (P-A)
West London Supranetwork Testicular Cancer Team
Standard Drug Regimens
EP/OMB + IT MTX
EP
Etoposide 150mg/m2
Cisplatin 25mg/m2
Cisplatin 25mg/m2
Cisplatin 25mg/m2
Alternating weekly with
OMB-CNS
Day 1
Vincristine 1mg/m2
Methotrexate 500mg/m2
Methotrexate 500mg/m2
Day 2
Bleomycin 15,000iu
Bleomycin 15,000iu
Folinic acid 15mg every 6 hours for 10 doses starting 32 hours after the start of the MTX
Intra-thecal methotrexate 12.5mg is given with the EP week and followed by Folinic Acid 7.5mg at
+ 24hrs and + 48hrs.
151
Appendix 24.6
Advanced GCT post chemotherapy follow-up protocols
North West London Supranetwork Testicular Cancer MDT
Post Chemotherapy Follow-Up Protocol
(Seminoma and NSGCT)
At each attendance check neck and abdominal lymph nodes, nipples, contralateral testis and ask about
back aches and if patient performing testicular self examination
Appointment
schedule
1 month
Post therapy
2 months
3 months
4 months
6 months
8 months
10 months
1 year
15months
18 months
21 months
2 years
28 months
32 months
3 years
3.5 years
4 years
4.5 years
5 years
6 years
7 years
8 years
9 years
10 years
Date
Next
appointment
1 month
1 month
1 month
2 months
2 months
2 months
2 months
3 months
3 months
3 months
3 months
4 months
4 months
4 months
6 months
6 months
6 months
6 months
I year,
1 year
1 year
1 year
1 year
1 year
CT
Sites of
disease
CXR
AFP
hCG















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











? CT


? CT

? CT





CXR
altern
ate
visits
Late
effects



Notes
1/ If post treatment CT scan is not normal the case must be discussed at the Supranetwork MDT.
2/ Late effects parameters to be assessed at the indicated clinic visits include:
Blood pressure, height and weight,
Urea and creatinine, fasting cholesterol (HDL and LDL) triglycerides, fasting glucose, FSH, LH and
testosterone.
152
25.1 Urology Support Folder
West London Supranetwork Testicular Cancer MDT
Urology Outpatients Support Folder
Contents
1/ Overview of Urology Investigation and Management Protocol
2/ Surgical Assessment Check List
3/ Oncology Referral Proforma
4/ GP diagnosis confirmation letter
5/ Supranetwork Urology Management Info
6/ Supranetwork Oncology Contact Details
If you need further copies of any of the forms, please email me on
[email protected] and we can send you the appropriate file
153
West London Supranetwork Testicular Cancer MDT
Overview of Urology Investigation and Management Protocols
1/ Patients referred with a potential diagnosis of testicular cancer should be seen in the next clinic
of any of the urology consultants.
2/ Pre-operative investigations include US of the testes, CXR and tumour markers (LDH, AFP and
bHCG)
3/ The details of routine patients proceeding to orchidectomy should be emailed/phoned/or faxed/
using the proforma to either;
Charing Cross (Dr Savage, Prof Seckl),
Chelsea and Westminster (Dr Brock)
Mount Vernon (Prof Rustin)
Do not wait for the path report or the removal of stitches!
4/ The local clinical nurse specialist and the Supranetwork MDT co-ordinator must also be
informed
Edward Marshall at CXH
Tel
020 331 11674
Fax
020 331 11757
Deepa Tailor at MVH
Tel
01923 844 688
Fax
01923 844 719
5/ The patient will be registered at Charing Cross, Chelsea and Westminster or Mount Vernon and
the CT scans and other staging investigations organised by the Oncology teams at those hospitals
6/ The Oncology Centre will confirm the date/time of the first out-patients appointment at Charing
Cross, Chelsea and Westminster or Mount Vernon on the same day as receiving the fax/phonecall.
7/ Please confirm the Oncology clinic arrangements with the patient before discharge
Emergencies
Important note re High Risk Patients
Some testicular cancer patients present with advanced disease that can rapidly be life threatening.
These patients must be discussed with the oncology team at either CXH or Mount Vernon prior to
considering orchidectomy. Many of these patients need urgent chemotherapy, without any
delays/risks from surgery and the risk of wound infections etc.
Emergency High Risk contacts
Charing Cross 0208-846-1234 on call Med Onc SpR
Mount Vernon 0845 241 1299 on call Med Onc SpR
In case of difficulties
Dr Savage 078-244-99125
154
West London Testicular Cancer Supranetwork MDT
Investigation Proforma to be filed in the Urology Notes
Patient Details
Surgical Assessment Proforma/Notes Check List for Routine Orchidectomy Patients
The majority of patients with testicular cancer present with an obvious mass and should have a
limited number of investigations and then proceed to orchidectomy and Oncology referral.
Important Note re High Risk Patients
A few patients present with evidence of advanced disease such as; high markers, an abdominal
mass, lung mets or CNS symptoms. This group of patients must be discussed with the oncology
team prior to consideration of orchidectomy.
For the routine patients the following investigations should be performed pre-operatively;
Pre-Operative Investigations
Date
Result
Testicular Ultrasound
Chest X Ray
AFP
bHCG
LDH
Please indicate if a fitting prosthesis was discussed pre-operatively Yes
No
Post-Operative Investigations
Date
Result
AFP
bHCG
LDH
155
West London Supranetwork Testicular Cancer MDT
Oncology Referral Pro-Forma
Patient details
GP details
Date
Dear Oncology Team,
Please could you arrange to see this man with testicular cancer in your clinic. The orchidectomy date is ______
The patients urology care has been under the care of ;
Mr/Mrs ______________________
at ___________________________ Hospital.
The results of his pre-operative investigations were
Date
Result
Testicular Ultrasound
Chest X Ray
AFP
bHCG
LDH
Please indicate if a fitting prosthesis was discussed pre-operatively
Yes
No
A formal referral letter will follow shortly.
Please contact the patient via; Home phone
Mobile phone
In patient on
__________________
__________________
__________________
Yours sincerely
Bleep #
Please fax and post to one of;
Charing Cross (0208-383-5577 Dr Savage and Prof Seckl)
Chelsea and W (020746-8863
Dr Brock )
Mount Vernon (01923-844840 Prof Rustin)
156
West London Supranetwork Testicular Cancer MDT
GP diagnosis confirmation letter
Patient details
Date
Dear Dr
Your patient has recently been diagnosed with testicular cancer following an
orchidectomy performed on _________.
He has been referred to _______________________________ hospital for oncology
investigations and follow-up.
A full surgical discharge summary will follow shortly and the oncology unit will be
keeping you updated with his progress.
Yours sincerely
157
West London Testicular Cancer Supranetwork MDT
8/ Urological Surgical Management
Orchidectomy
Orchidectomy is rarely an emergency procedure and patients presenting out of hours should have
surgery performed on the next available day time list.
Radical orchidectomy is to be performed through an inguinal incision. The tumour bearing testicle
is resected along with the spermatic cord at the level of the internal inguinal ring.
Testicular Prosthesis
It is regarded as good practice that patients are offered the possibility of having a testicular
prosthesis fitted. There is some evidence that loss of the testis can result in some psychological
morbidity, however it is unclear how helpful a prosthesis is in coping with this.
It is regarded as good practice by COIN, NICE and the DoH that the option of having a prosthesis
fitted at the time of orchidectomy is discussed and that this discussion and the outcome are
recorded in the notes. Additionally the Supranetwork require that this discussion/outcome is
recorded on the referral form.
Contra-indications to initial orchidectomy
As detailed in section 7, patients who may have advanced testicular cancer should not proceed
directly with a routine orchidectomy. These patients must be discussed with one of the medical
oncology teams directly by phone. Do not wait for the next MDT meeting.
Contralateral Testis Management
Approximately 1.5% of testicular cancer patients develops bilateral disease. Whilst synchronous
presentation with bilateral tumours is rare, a considerable number of patients present with
potentially pre-malignant changes in the contralateral testis.
Whilst there is not yet a consensus on how best to manage these patients with potential premalignant changes a biopsy to look for TIN/CIS can be particularly considered if:
A history of maldescent
Testicular volume <12ml
multifocal punctate calcification
The option of contralateral testicular biopsy should be discussed with the patients at high risk of
TIN.
Indications for Consideration of Partial Orchidectomy
This may be an alternative to orchidectomy in small primary tumours, however this approach is
experimental and is not yet part of standard routine practice.
However partial orchidectomy may be considered, following discussion with the patient and the
Supranetwork MDT, in case of patients with:
Synchronous bilateral testis tumours
Metachronous contralateral (second) testis tumour
Tumour in a solitary testis and adequate endocrine function
Post-Orchidectomy Care and Investigations
It is helpful if the tumour markers (LDH, AFP and bHCG) can be repeated post-operatively.
158
9/ Referral to Oncology, MDT discussion, Pathology Review Supranetwork procedures
Referral to the oncology team at Charing Cross, Chelsea and Westminster or Mount Vernon
Hospitals should take place on or before the day of the orchidectomy, there is no need to wait for
either the pathology result or for the urological out patient follow-up appointment.
Ensuring the security of the referral should be achieved by a two stage system,
1/ Phoning the oncology teams involved;
CXH
Dr Savage
0208-846-1419
Prof Seckl
0208-846-1421
Chelsea and Westminster
Dr Brock
0208-846-5054
Mount Vernon
Prof Rustin 01923 844389
2/ The patient’s details should be faxed through on the referral proforma sheet APP 9.1 which
should be sent to;
CXH
Dr Savage
Prof Seckl
Fax 0208-383-5577
Fax 0208-383-5577
Chelsea and Westminster
Dr Brock
0208-746-8863
Mount Vernon
Prof Rustin 01923 844840
Arrangement and Confirmation of Oncology outpatients appointment and Pathology Review
Request
On receipt of the referral the Oncology team will confirm the date of the first outpatient
appointment for that patient. This information will be relayed to the referring urology team or
directly to the patient. The details of the first appointment and the route this was relayed to the
patient will be recorded in the Oncology notes.
Additionally the oncology team will at the point of receipt of the referral send a request for central
review of the pathology to the Histopathology team at the urology unit. A standard letter to
expedite this request is included.
159
25.2 Oncology Support Folder
West London Supranetwork Testicular Cancer MDT
Oncology Outpatients Support Folder
Contents
1/ Oncology Initial Assessment
2/ Tumour Markers
3/ Initial Assessment Checklist
4/ GP diagnosis confirmation letter
5/ Pathology Request Letter
6/ Stage I seminoma surveillance protocol
7/ Stage I NSGCT surveillance protocol
8/ Supranetwork policies for advanced GCT
9/ Staging System
10/ Sperm storage guidance
11/ Sperm storage referral letter
12/ IGCCCG groups and pre-treatment assessment
13/ 1st line chemotherapy
14/ Post chemotherapy follow-up protocol
160
West London Testicular Cancer Supranetwork MDT
1/ Oncology Initial Assessment
[1A-237, 2G-339]
To help with the initial Oncological assessment a Proforma is included in APP 10.1. The Proforma
gives a list of all the standard investigation and space to include information about the
identification of the Key Worker and the discussion regarding any permanent records of
consultations. Additionally the Proforma includes a check to ensure that the pathology review has
(already) been requested.
Key Worker
[2G-320]
It is the policy of the Supranetwork that at the time of the patients first attendance at the Oncology
unit that the patient is informed of their key worker. It is the role of the key worker to co-ordinate
the patients care, promote continuity and ensure the patient know who to access for information and
advice. It is the expectation of the MDT that the Consultant Oncologist of the patient will be the
key worker for the majority of patients.
Permanent record of Consultation
[2G-335]
It is a policy of the Supranetwork MDT that patient can request copies of any/all clinical letters and
may request a tape recording of any out-patient consultation. However tape recordings are not made
routinely and the MDT will need advance notice of this requirement.
The request can be to the Consultant in charge or via the patient’s key worker.
Supranetwork Policy on Routine Staging Investigations for Testicular Cancer
[2G-346]
The policy of the Supranetwork group is for most of the post orchidectomy staging investigations
to be performed at the Oncology treatment centre. In particular the staging CT scan in patients who
do not clinically appear to have advanced disease should be performed by their Oncology team at
their treatment centre. However the patients LDH and tumour markers should be checked post
operatively at the urology unit if the patient remains an in-patient for more than 1 day.
Standard Oncological Staging Investigations
For patients with presumed stage I disease the standard post operation staging investigations should
comprise;
CT Thorax Abdomen and Pelvis
CXR
HCG/AFP/LDH
Full blood count
Biochemistry
Central review of pathology
Charing Cross Hospital tumour marker follow-up service
All patients within the Supranetwork with testicular cancer should be registered with the Charing
Cross tumour marker follow-up service irrespective of their tumour marker status. This system
ensures that marker follow-up is co-ordinated with the protocols particularly in the first 6 months of
treatment when marker follow-up testing is more frequent than the monthly clinic visit.
Contact details of the Charing Cross marker follow-up service
Tel 0208-846-1409
Fax 0208-383-5577
161
Background information on tumour markers in Testicular cancer
The table below shows the approximate incidence of marker production in the differing pathology
types in germ cell tumours. However it should be noted also that the pattern of marker production
can alter with progression of the disease as the results of the study shown below confirms;
Histology of Primary Germ Cell Tumours and Frequency of Serum Tumour
Markers
Presence of tumour markers by cell type (%)
Frequency by cell type
(%)
AFP
HCG
All germ cell tumours
Seminoma
Nonseminomatous germ cell
tumours
Embryonal cell carcinoma
Teratocarcinoma
Teratoma
Choriocarcinoma
100
42
58
50 to 75
0
65
40 to 60
9
56
26
26
5
1
70
64
37
0
60
57
25
100
Yolk sac
<1
75
25
Tumour type
AFP=alpha-fetoprotein serum half life 3-5 days; HCG=human chorionic gonadotropin serum half life 1-2 days.
The value and limitations of markers in the diagnosis of recurrent disease.
For more information see Trigo et al; Cancer 2000; 88 162-8
Records of 794 patients with GCTs
123 went on to relapse
12/36 seminoma were marker positive
67/87 teratoma were marker positive
At diagnosis of relapse
Seminoma
36 patients relapsed of whom 16 were marker positive (10 who had been hCG positive at initial diagnosis and 6 who
were initially marker negative)
NSGCT
87 patients relapsed of whom 60 were marker positive (48 who had been hCG positive at initial diagnosis and 12 who
were initially marker negative). The paper also showed that patients who were marker +ve at diagnosis can relapse with
marker –ve disease.
Conclusion
Overall the pattern at diagnosis and relapse only correlated in 56 of the 87 pts (64%)
Markers need to measured in all GCT patients as per protocols and can be of value in both pts with disease that is
initially marker + ve and marker –ve.
162
West London Supranetwork Testicular Cancer MDT
Initial Oncology Assessment Checklist
[2G-339]
The following should be arranged at the patient’s initial visit to the Oncology Treatment Centre.
Investigations
CT Scan Thorax Abdomen and Pelvis
Full blood count
Biochemistry
Tumour markers AFP, hCG, LDH
CXR
Documentation
Please document the following
1/ Pathology review already requested
Yes
If No Pathology review requested today
Yes
2/ Has Key Worker been identified
No
Yes
No
If Yes Who is it
3/ Has the Supranetwork Testicular MDT information on testicular cancer been given?
Yes
No
4/ Has a permanent record of the discussion regarding treatment options been offered?
Yes
No
163
West London Supranetwork Testicular Cancer MDT
APP 9.3 GP diagnosis confirmation letter
Patient details
Date
Dear Dr
Your patient has recently been diagnosed with testicular cancer following an
orchidectomy performed on _________.
He has been referred to _______________________________ hospital for oncology
investigations and follow-up.
A full surgical discharge summary will follow shortly and the oncology unit will be
keeping you updated with his progress.
Yours sincerely
164
West London Supranetwork Testicular Cancer MDT
APP 9.2 Pathology Request Letter
Patient details
Date
Dear Dr
This patient has recently been referred to Charing Cross Hospital with a provisional
diagnosis of testicular cancer following an orchidectomy performed on _________,
under the care of _______________.
It is the policy of the Supranetwork Testicular Cancer MDT to arrange a central
review of the pathology of these patients at the earliest opportunity.
We would be grateful if you could forward representative slides and blocks to allow
this.
Please send the samples to;
The GTT centre
Department of Medical Oncology
Charing Cross Hospital
Fulham Palace Rd
London
W6 8RF
Tel 0208-846-1409
Fax 0208-383-5577
Yours sincerely
Dr Savage/Prof Seckl
Consultant in Medical Oncology
Charing Cross Hospital
165
West London Supranetwork Testicular Cancer MDT
APP 12.2 Standard Surveillance Protocol
[2G-329]
Stage I Seminoma and marker –ve NSGCT
Clinic Visits
Year 1
Year 2
Year 3
Year 4
Year 5 and 6
Year 7 onwards
CXR + clinical exam monthly
CT Thorax +Abdo at + 3 months
CT Thorax +Abdo at + 6 months
CT Thorax +Abdo at + 12 months
CXR + clinical exam 2 monthly
CT Thorax +Abdo at + 24 months
CXR + clinical exam 3 monthly
CXR + clinical exam 4 monthly
CXR + clinical exam 6 monthly
Clinical exam 12 monthly
Stage I GCT Tumour Marker Surveillance
Serum AFP and HCG and LDH
0 - 6 months
7 - 12 months
Year 2
Year 3
Year 4
Year 5 and 6
Year 7 onwards
2 weekly
1 monthly
2 monthly
3 monthly
4 monthly
6 monthly
annually
166
West London Testicular Cancer Supranetwork MDT
Standard Surveillance Protocol
Stage I NSGCT surveillance
Clinic Visits
Year 1
Year 2
Year 3
Year 4
Year 5 and 6
Year 7 onwards
CXR + clinical exam monthly
CT Thorax and Abdo at + 3 months
CT Thorax and Abdo at + 12 months
CXR + clinical exam 2 monthly
CXR + clinical exam 3 monthly
CXR + clinical exam 4 monthly
CXR + clinical exam 6 monthly
Clinical exam 12 monthly
Stage I NSGCT Tumour Marker Surveillance
Serum AFP and HCG and LDH (regardless of initial value)
0 - 6 months
7 - 12 months
Year 2
Year 3
Year 4
Year 5 and 6
Year 7 onwards
2 weekly
1 monthly
2 monthly
3 monthly
4 monthly
6 monthly
annually
167
13/ Supranetwork MDT Policies for The Management of Advanced Germ Cell Tumours of
the Testis
Overview
The management of advanced testicular GCT is predominantly with the use of cisplatin based
chemotherapy.
To ensure adequate management and avoid over-treatment, patients should be staged and their
prognostic grouping worked out using the IGCCCG standards as shown below.
Advanced Disease Pre-treatment Investigations
CT Thorax Abdomen Pelvis
MRI Brain
GFR
Tumour markers LDH, AFP, bHCG
Sperm storage (see APP 13.2 and 13.3)
Pulmonary Function Tests
Patients with risk factors for bleomycin pulmonary toxicity, such as previous radiotherapy, smokers, age over 40 or
poor renal function should have lung function including VC and Kco as agreed locally
A checklist, treatment guide and summary of the IGCCCG groups is provided on form APP 13.1 which should be
completed and filed in the patients notes prior to starting chemotherapy.
IGCCCG Prognostic Groups and Historical Cure Rates
Teratoma (NSGCT)
Seminoma
Good prognosis with all of:
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
AFP<1000 ng/ml
HCG<5000 iu/l
LDH<1.5 upper limit of normal
56% of teratomas
5-year survival 92%
Any primary site
No non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
90% of seminomas
5-year survival 86%
Intermediate prognosis with all of:
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
AFP1000 and10000 ng/ml
or HCG 5000 and  50000 iu/l or
LDH  1.5 normal  10 normal
28% of teratomas
5-year survival 80%
Any primary site
Non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
10% of seminomas
5-year survival 73%
Poor prognosis with any of:
Mediastinal primary or non-pulmonary
visceral metastases
AFP>10,000 ng/ml or
HCG>50,000 iu/l or
LDH>10 normal
16% of teratomas
5-year survival 48%
No patients classified as poor prognosis
168
Testicular Germ Cell Tumours Staging System
Whilst the management of advanced testicular cancer is mainly determined by the IGCCCG
prognostic grouping. When appropriate the Supranetwork also uses the Royal Marsden Staging
system as shown below
RMH Staging
I No evidence of disease outside the testis
IM As above but with persistently raised tumour markers
II Infradiaphragmatic nodal involvement
IIA Maximum diameter <2 cm
IIB Maximum diameter 2-5 cm
IIC Maximum diameter >5-10 cm
IID* Maximum diameter >10 cm
III Supra and infradiaphragmatic node involvement
Abdominal nodes A, B, C, as above
Mediastinal nodes M+
Neck nodes N+
IV Extralymphatic metastases
Abdominal nodes A, B, C, as above
Mediastinal or neck nodes as for stage 3
Lungs:
 L1 <3 metastases
 L2 Multiple metastases <2 cm maximum diameter
 L3 Multiple metastases >2 cm in diameter
Liver involvement H+
Other sites specified
169
West London Supranetwork Testicular Cancer MDT
Sperm storage
Supranetwork Policy on Sperm Storage
All patients should be offered sperm storage prior to chemotherapy or radiotherapy, even if they
have oligospermia. The only exceptions to this are patients who need urgent chemotherapy.
It is the policy of the Supranetwork that the outcomes of discussions and decisions about sperm
storage are included in the patients case notes.
Sperm storage cryopreservation is performed via the Andrology laboratory, Hammersmith Hospital
– Dr Kevin Lindsay, Principal Clinical Scientist in Andrology.
Contact details
0208 383-4680
Tel Fax
0208 383-3591
For patients proceeding to sperm storage HIV and Hep B&C status must be checked.
However the patient can proceed with sperm storage whilst the virology tests are being processed.
A standard referral letter is attached in appendix APP 13.3.
170
Please Fax to 0208 383-3591
Date
Re
Dear Andrology Unit,
Thank you very much for arranging sperm storage for this man who we discussed on the phone today. He has recently
been diagnosed with testicular cancer and would like to perform sperm storage
We have already taken blood serology for Hep B, Hep C and HIV and await the results.
Thank you for your help
Yours sincerely
Philip Savage/Michael Seckl
Consultant in Medical Oncology
Charing Cross Hospital
London
W6 8RF
Tel 0208-846-1419/1421
Fax 0208-383-5577
171
West London Supranetwork MDT Testicular Cancer Treatment Plan
Name
Pathology
DoB
IGCCCG Group
Consultant
Treatment Plan
IGCCCG Prognostic grouping
Teratoma (NSGCT)
Seminoma
Good prognosis with all of:
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
AFP<1000 ng/ml
HCG<5000 iu/l
LDH<1.5 upper limit of normal
56% of teratomas
5-year survival 92%
Any primary site
No non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
90% of seminomas
5-year survival 86%
Intermediate prognosis with all of:
Testis/retroperitoneal primary
No non-pulmonary visceral metastases
AFP1000 and10000 ng/ml
or HCG 5000 and  50000 iu/l or
LDH  1.5 normal  10 normal
28% of teratomas
5-year survival 80%
Any primary site
Non-pulmonary visceral metastases
Normal AFP
Any HCG
Any LDH
10% of seminomas
5-year survival 73%
Poor prognosis with any of:
Mediastinal primary or non-pulmonary visceral
metastases
AFP>10,000 ng/ml or
HCG>50,000 iu/l or
LDH>10 normal
16% of teratomas
5-year survival 48%
No patients classified as poor prognosis
MDT treatment options by IGCCC Prognostic group
Good Prognosis
BEP x 3 or
EP x 4
Intermediate Prognosis
BEP x 4 or POMB/ACE (5)
Poor Prognosis
POMB/ACE (7) or BEP 4
Poor prognosis with cerebral Mets at presentation
EP/OMB plus IT MTX
Pre-treatment investigations for cycle 1
CT TAP
MRI brain
GFR and repeat prior to cycle 3
Sperm storage if time permits
Respiratory function tests and repeat prior to cycle 3
Aim to avoid routine anti-emetic steroids
172
West London Testicular Cancer Supranetwork MDT
Standard Drug Regimens for 1st line use
[1A-234]
Carboplatin
AUC 7 (EDTA measured clearance)
BEP 5 day
Given over
Cisplatin
Etoposide
Bleomycin
5 Days
20mg/m2
100mg/m2
30mg
3 weekly cycle
D1-5
D1-5
D1, 8, 15
EP 5 day
Given over
Cisplatin
Etoposide
5 Days
20mg/m2
100mg/m2
3 weekly cycle
D1-5
D1-5
173
West London Supranetwork Testicular Cancer Team
Standard Drug Regimens
POMB/ACE
POMB
D1
Vincristine 1mg/ m2 iv bolus
Methotrexate 100mg/ m2 iv bolus
and then 200mg/ m2 iv for 12 hours
D2
Bleomycin 30mg by 24 hour iv infusion
Folinic acid 15mg po 6 hourly x 4 given at 24,36,48 and 60hrs post MTX.
D3-4
Cisplatin 40mg/ m2 with hydration
Cisplatin 40mg/ m2 with hydration
Cisplatin 40mg/ m2 with hydration
ACE
D1
Etoposide 100mg/ m2
Actinomycin D 0.5mg
D2
Etoposide 100mg/ m2
Actinomycin D 0.5mg
D3
Etoposide 100mg/ m2
Actinomycin D 0.5mg
Cyclophosphamide 500mg/m2
Treatment interval 2 weeks
Treatment sequence P-P-A-P-A- (P-A)
174
West London Supranetwork Testicular Cancer MDT
Standard Follow-up Protocols
Follow-up after chemotherapy for advanced Seminoma and NSGCT
[2G-329]
Clinic visits
Year 1
Year 2
Year 3
Year 4 and 5
Year 6 onwards
monthly clinic visits
CT scan at + 3 months only if the end of treatment CT scan was suspicious
of residual disease
2 monthly clinic visits
3 monthly clinic visits
6 monthly clinic visits
annual visits
Note CXR should be performed at alternate visits and stopped at the end of year 3
Blood pressure and urea/creatinine should be checked and recorded annually after 3 years
Tumour Markers Follow-up after chemotherapy for advanced Seminoma and
NSGCT
Serum AFP, hCG and LDH
Year 1
Year 2
Year 3
Year 4 and 5
Year 6 onward
monthly
2 monthly
3 monthly
6 monthly
Annually
175
Mount Vernon
Cancer Network
Appendix 3
URGENT TWO WEEK REFERRAL. SUSPECTED UROLOGY CANCER
This form to be used only if the patient fulfils the following criteria.
PATIENT DETAILS
Surname
GP DETAILS
Title
Forename (s)
Name
Practice Code
DOB
Age
Telephone
NHS Number
UBRN
Fax
Address
Postcode
Practice name/address
Telephone
Home
Postcode
Work
Translator required
Mobile
Specify language
Confirm that the patient has been given a 2-week wait referral information leaflet.
Confirm that the patient understands this is a referral to rule out suspected cancer.
Confirm that the patient is willing and able to attend in the next 2 weeks.
PROSTATE CANCER Either
hard, irregular prostate on digital rectal examination (DRE)
Or
raised/rising age specific PSA
Please, specify PSA level _______ ng/ml
RENAL CANCERmass arising from urinary tract, specify
abdominal or
If confirmed by imaging, please fax report
BLADDER / UROTHELIAL CANCER –
pelvic
painless macroscopic haematuria - persistent after exclusion or treatment of UTI
patient > 40 yrs with recurrent/persistent UTI and haematuria
patient >50 yrs with unexplained microscopic haematuria
strongly positive dipstick or laboratory proven only
TESTICULAR CANCERswelling within the body of the Testis
PENILE CANCERprogressive ulceration
lump/mass
Additional information / other reasons for requesting urgent referral.
other primary cancer, specify site
Please attach (if appropriate) printout of PMH, drugs and any other relevant information.
FAX East & North Herts NHS Trust: 01438 781835
If you have not received acknowledgement within 48hrs (Mon-Fri) please telephone 2/52 Wait Supervisor on
01438 285206.
FAX West Herts Hospitals Trust: 01727 897492
FAX Luton & Dunstable NHS Foundation Trust: 01582 497910 or 497911
FOR HOSPITAL USE ONLY
Date referral received:
1st appt date:
If 1st appt not accepted give reason/s:
2nd appt date reason/s:
MVCN Urology NSSG agreed December 2010
176
Urgent “2 week wait” referral to Hospital
Why have I been referred to the hospital?
Your General Practitioner (GP) or Dentist has
asked for an urgent hospital appointment for
you, because you have symptoms that might
indicate cancer.
Does this mean I have cancer?
After the examination, we find that most
patients who come to us do not have cancer,
but another condition.
hospital for any reason, within two weeks
after you have seen your GP.
The hospital will send you an appointment
letter within a week; if there is not sufficient
time to send you a letter they will contact you
by phone.
Let your GP surgery know if you have not
heard from the hospital a week after you
have seen your GP.
So why has my GP referred me?
GP’s can diagnose and treat most complaints
and illnesses themselves. However, on some
occasions they need to arrange for you to
have a hospital assessment, so that you can
see a specialist hospital doctor. The “two
week wait” appointment system was
introduced so that you can have
investigations done and be seen as quickly
as possible.
There could be several reasons why your
doctor has sent you for a special test, for
instance,




Your symptoms need further investigation
The treatment already prescribed has not
worked
Investigations your GP arranged have shown
some abnormal results
To make sure you don’t have a serious
disease.
Will I need any tests?
You may require specialised tests and these
tests may take place either before your first
appointment with the specialist hospital
doctor, or during it. This will help the doctor to
understand the cause of your symptoms.
What do I need to do now?
Make sure that your GP has your correct
address and telephone number, including
mobile number, if possible.
It is very important that you are available to
attend an appointment within two weeks of
seeing your GP. Please tell your GP if you if
you are likely to be away, or unable to attend
If you are unable to attend the appointment
sent to you, please phone the hospital
immediately. It is important that you arrange
another date and time if you have to cancel
an appointment.
Your Hospital Appointment
At your first appointment, based on the
information from your GP and your
consultation with the hospital doctor, the
clinic staff will give you more information
about what will happen next.
Please feel free to bring someone with you to
your appointment.
If you have any queries regarding the
arrangements for your appointment, please
telephone the hospital you have been referred
to on one of the numbers below Monday to
Friday 8.30am - 5.00pm
East & North Herts NHS Trust:
Two-week-wait office: 01438 285206
West Herts Hospitals Trust:
Two-week-wait office: 01727 897199
Luton & Dunstable Hospital Trust
Outpatient Appointment line: 0845 1270193
Further Information
NHS Choices (Guide to waiting times)
www.nhs.uk/
NICE (Clinical Guidelines, Referral for
Suspected Cancer) www.nice.org.uk
177
Appendix 4
ABBREVIATIONS USED IN THIS DOCUMENT
ARCO
ARCON
accelerated radiotherapy with carbogen
accelerated radiotherapy with carbogen nicotinamide
ASCO
CIS
CISCA
CMV
EAU
EORTC
American Society of Clinical Oncology
carcinoma in situ
cisplatin, cyclophosphamide plus adriamycin
cisplatin, methotrexate plus vinblastine
European Association of Urology
European Organization for Research and Treatment of Cancer
FACT
Functional Assessment of Cancer Therapy
GC
gemcitabine plus cisplatin
HD-MVAC high-dose methotrexate, vinblastine, adriamycin plus cisplatin
HRQL
MRC
MVAC
health-related quality of life
Medical Research Council (UK)
methotrexate, vinblastine, adriamycin plus cisplatin
SCC
SF-36
squamous cell carcinoma
Short Form-36
SWOG
TCC
TNM
TUR
TURB
UICC
WHO
Southwest Oncology Group
transitional cell carcinoma
Tumor, Node, Metastases
transurethral resection
transurethral resection of bladder
tumour
Union International Contre le Cancer
World Health Organization
`London
and South East Sarcoma Network
Shared Care Pathway for Soft Tissue Sarcomas Presenting to Site
Specialised MDTs
Urology
Background
This guidance is to provide direction for the management of patients with sarcomas that may present through
urology cancer services and to define the relationship that should exist with the specialist sarcoma MDT.
This guidance refers to the care of patients in the London and South East Sarcoma Network and therefore
recognises that specialist services for soft tissue sarcomas are provided by the Sarcoma Unit at The London
Sarcoma Service provided through joint working of UCLH and RNOH.
Principals
This guidance is being developed in accordance with the relevant measures in the Manual for Cancer
Services: Sarcoma Measures and the Manual for Cancer Services: Urology Measures. They are also written
in accordance with the LSESN referral guidelines (see www.lsesn.nhs.uk) and the LSESN Patient
Management Policy.
1) Notification
All sarcoma patients presenting to a local or specialist Urology MDT should be notified to the sarcoma MDT
nominated in the local network urology cancer operational policy.
2) Review by Sarcoma MDT
a) Pathology
All urology sarcomas will have pathology review undertaken by the nominated specialist sarcoma
pathology service (for details see MDT operational policies).
b) Management
Management of all new soft tissue sarcomas sarcomas will referred to the sarcoma MDT. Early
referral from the time of suspicion or biopsy is recommended.
3) Site of Definitive Treatment
Discussion between MDT’s will take place to determine the appropriate hospital for definitive excision. Initial
surgical treatment may be undertaken by the local or specialist urology team. It is preferred that complex
surgery, i.e. multivisceral resection or operations requiring complex reconstructive procedures, and second
operations take place at a sarcoma centre.
Chemotherapy and radiotherapy will be undertaken by designated practitioners as agreed by the SAG.
4) Recurrence
All recurrent urology sarcomas will be discussed and reviewed by the sarcoma MDT.
Presentation
Diagnosis
Treatment
Follow up
Role and Responsibility
Specialist/Local Urology
Sarcoma MDT/Clinic
MDT/Clinic
Assess new cases of suspected
urology cancer
Notify Sarcoma MDT of all new cases
of urology sarcoma
Refer all cases of urology sarcoma for Review pathology of all new cases
pathology review
of urology sarcoma
Refer all new cases of urology
Clinical review of all new cases
sarcoma for review by sarcoma MDT
Initial surgery
Complex surgery and second
operations
All chemotherapy
All radiotherapy
Follow up according to agreed
Follow up in accordance with
Urology MDT guidelines
sarcoma follow up guidelines of all
patients treated by the sarcoma
MDT
Pathway Summary:
Secondary Care
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MDT Coordinator Contact details:
LondonSarcomaService:nhs.net
20 3447 4821
GP (less likely)
A&E
Suspected urological (kidney, bladder, prostate and testis) sarcoma
Signs/symptoms
Imaging (CT/MRI)
Post-operative diagnosis
Refer to London Sarcoma Service
Refer to local Urological team
or
Notify sarcoma MDT of
all sarcoma patients
All histology
reviewed by
Specialist
Sarcoma
Pathologist
Sarcoma MDT
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Patient age under 18 or 18-21 solid tumour
peads MDT or TYAC MDT
Urology MDT
Register patient
Review diagnosis
Plan management
Discussion between MDTs - invite Urology
team to attend Sarcoma MDT
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Register patient
Review diagnosis
Plan management
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Register patient
Review diagnosis
Plan management
MDT Plan:
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Refer to GP/local trust
as appropriate
Palliative Care
Diagnostics/Biopsies
Radiology
Identification of treatment centre
OPD
Results, Treatment plan, CNS Contact
Follow Up*
Recurrence
Surgery
Complex surgery and
second operations to be
done at sarcoma centre
Chemotherapy +/- Radiotherapy
* Follow Up according to
agreed urology MDT guidelines
and LSESN sarcoma follow-up
guidelines (for those patients
treated by sarcoma MDT)