Download Guidelines for the Management of Prostate Cancer

Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Guidelines for the Management
of Prostate Cancer
(14-1C-113g)
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INTERIM
Updated, Approved and Published: May 2014
Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Title: Guidelines for the Management of Prostate Cancer
Authors: Vivekanandan Kumar and Rob Brierly
Document management
Document ratification and history
Date placed on electronic
library:
Approved by:
Urology NCG Co-Chair s
Review period:
2 years (or earlier in the light of new evidence)
Amended items
Prostate Biopsy update (Feb 2014)
Management of erectile function post radical prostatectomy and radiotherapy (Feb 2014)
Authors:
Vivekanandan Kumar and
Rob Brierly
Version number as approved and published:
2014 v2.2
May 2014
Document Owner:
Anglia Cancer Network
www.angliacancernetwork.nhs.uk
Unique identifier no.:
AngCN-U
EoE SCN Cancer
The process of review, update and approval of this document has been signed-off by Dr Rory Harvey,
the EoE SCN, Clinical Director for Cancer. June 2014
For comments / amendments to these guidelines, please contact:
Name
Vivekanandan
Kumar
Robert Brierly
Hospital
Tel. No
Email
NNUH
[email protected]
Ipswich
[email protected]
For copies of guidelines, please refer to the Anglia Cancer Network website:
www.angliacancernetwork.nhs.uk
Monitoring the effectiveness of the Process
a) Process for Monitoring compliance and Effectiveness - Review of compliance as determined by audit.
Any non compliance to be presented by PQ Manager to the AngCN Business Meeting on an annual basis –
the minutes of this meeting are retained for a minimum of five years.
b) Standards/Key Performance Indicators – This process forms part of a quality system working to, but not
accredited to, International Standard BS EN ISO 9001:2008. The effectiveness of the process will be
monitored in accordance with the methods given in the quality manual, AngCN-QM
Disclaimer
It is your responsibility to check against the electronic library that this printed out copy is the most
recent issue of this document.
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
CONTENTS
Page No
INTRODUCTION ........................................................................................................................... ……… 4
REFERRALS ........................................................................................................................................... 4
PROSTATE BIOPSY ............................................................................................................................... 4
LMDT REVIEW........................................................................................................................................ 5
STAGING ................................................................................................................................................ 5
DEFINING TUMOUR STAGE AND GRADE ........................................................................................... 5
MANAGEMENT OPTIONS FOR EARLY PROSTATE CANCER ........................................................... 5
1. Active Surveillance
6
2. Radical Prostatectomy
6
3. Radioactive seed implantation – Brachytherapy
7
4. External Beam Radiotherapy – EBRT ………………………………………………………… 7
6. Long term androgen deprivation therapy alone
8
MANAGEMENT OPTIONS FOR LOCALLY ADVANCED PROSTATE CANCER (WITHOUT
METASTASES) T3B/T4 N0/1 M0 ........................................................................................................... 8
MANAGEMENT OF ERECTILE DYSFUNCTION POST RADICAL TREATMENTS ............................. 9
SALVAGE THERAPY FOR RECURRENT PROSTATE CANCER POST-RADIOTHERAPY ............... 9
MANAGEMENT OPTIONS FOR METASTATIC DISEASE .................................................................... 10
THERAPY FOR PAINFUL BONE METASTASES ................................................................................. 11
OTHER CONSIDERATIONS ................................................................................................................... 12
SMALL CELL CARCINOMA ................................................................................................................... 12
FOLLOW UP ........................................................................................................................................... 12
APPENDICES ......................................................................................................................................... 15
Appendix 1 – Prostate histology, grading
16
Appendix 2 - Staging
17
Appendix 3 – Osteoporosis Guidelines
18
Appendix 4 - Clinical Trials
19
Appendix 5 – Prostate Cancer Pathway (14-1C-113g)
20
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Introduction
The purpose of this manual is to collate the numerous guidelines that exist, into a working manual
for the management of prostate cancer within the Anglia Cancer Network. It should act as a
summary guide for the management of patients with prostate cancer based on the available
published evidence. Its scope is to aid all health practitioners involved with the patient from
primary care and referral through treatment to follow up. However, as constant modifications are
being made, these guidelines should only be used to give an indication of current management.
They should not be used to treat patients without checking that changes have not been made.
These guidelines have been developed by discussion between clinicians within the Anglia Cancer
Network Urology Network Cancer Group (NCG) but without the establishment of a formal guideline
development group. These guidelines have been endorsed by the Anglia Cancer Network Urology
NCG. They will be reviewed and updated on an annual basis or more frequently as required.
The guidelines are intended as a working document for daily practice. For more detailed sources,
and for educational material, please refer to guidelines produced by e.g. NICE, BAUS, EAU, AUA.
Referrals
For referrals from Primary and Secondary Care, see AngCN prostate cancer pathway Appendix 5
– Prostate Cancer Pathway and DH suspected cancer guidance.
Prostate biopsy
The following can be considered as indications for biopsy:

Any patient with PSA > age adjusted upper limit (ULN)

Any patient with a raised PSA needs a LUTS assessment

Other men who wish to have a biopsy based on their PSA and general level of risk

Any patient with palpably abnormal prostate.
A minimum of ten samples should be taken to reduce the risk of underestimating tumour grade.
In patients with continued suspicion of prostate cancer, after first negative biopsy, either in the
form of rising PSA, change in DRE findings or MRI changes, a TRUS + Trans perineal template,
biopsies should be considered for subsequent biopsy to reduce false negative results, especially
from the anterior part of the prostate gland and reduce underestimating the cancer grade of the
cancer if found. An MRI before repeat biopsies should be considered after discussions with the
local MDT.
See AngCN Pathology guidelines for details of pathology assessment of biopsy material.
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
LMDT review
All positive prostate biopsies should be discussed in the LMDT.
The need for staging investigations can be based on the prostate cancer risk categories devised
by D’Amico.
Low Risk -T1c or T2a, Gleason <6 and PSA <10 ug/l
Intermediate Risk - T2b or Gleason 7 or PSA >10 and < 20 ug/l
High Risk - > T2c or Gleason > 8 or PSA > 20 ug/l
Staging

Bone scintigram in all patients in intermediate and high risk categories, or if bone pain.

MR pelvis should be considered in all patients being considered for radical therapy and in all
patients considered for active surveillance. MRI should be performed at least three weeks after
biopsy (dependent on individual centre) to allow changes due to bleeding from biopsy to
subside.
Defining Tumour Stage and Grade
Pathology and tumour grade
The recommended histological grading system for adenocarcinoma is described by Gleason (see
Appendix 1).
Tumour stage
In the UK the TNM is used (see Appendix 2)
Management options for early prostate cancer
Patients will have been assigned a D’Amico Risk Category – low, intermediate or high.
For most patients with early stage prostate cancer there are will be a number of options available.
These should be discussed with the patient. All patients with prostate cancer being considered for
surgery or brachytherapy should be discussed with the Specialist Multi-disciplinary Team at
Addenbrooke’s or the Norfolk and Norwich University Hospital, and counselled initially by the local
urological and oncological core members of their LMDT.
The main management options include:
1.
2.
3.
4.
5.
6.
Active surveillance
Radical prostatectomy
Radioactive seed implantation - Brachytherapy
External Beam Radiotherapy
Watchful wait
Hormone therapy alone
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
1. Active Surveillance
Type of patient who may be considered:







>10 years life expectancy
Gleason sum 6 or 7(3+4) (well/moderately well differentiated) tumours
T1/T2a and T2b
PSA<10
Asymptomatic
Patient preference
Men with intermediate risk cancer who do not wish to have immediate radical treatment
Baseline MRI should be considered for all patients contemplating active surveillance. The risk of
progression is related to grade and stage. These risks should be explained to the patient. If the
patient opts for active surveillance and he is suitable for radical treatment should his disease
progresses, he should be followed up initially at three monthly intervals with a PSA and also rectal
examination at least every 12 months. At a later stage once stability of the PSA reading has been
established, the appointment interval may be increased to 6 monthly. Monitoring should include a
measure of PSA doubling time (PDAdt). Active surveillance should involve repeat prostate
biopsies every 12 to 18 months.
The patients managed may be informed by the PSAdt, some suggestions are put below but
patient choice remains paramount.



PSAdt <10 months – intervention
PSAdt >4 years – no intervention / continued active surveillance
PDAdt between 10 months and 4 years – consider treatment according to patient
parameters (i.e. Radical or palliative treatment).
 Progression in repeat biopsies (eg. grade shift, increased tumor volume) should trigger
intervention
Patients with less than 10 years of life expectancy, older or serious medical conditions should be
offered watchful wait.
2. Radical Prostatectomy
Usually men undergoing radical prostatectomy would have the following criteria.





Patients with a predicted life expectancy in excess of 10-15 years; usually these men will be
aged under 73 years.
T1/T2N0M0 and PSA < 20 ug/l
Some men with operable cT3 disease may wish for surgery
Patient understands and accepts the risk of impotence and/or incontinence.
Patient preference.

Prostatectomy may be advantageous if there is a history of marked LUTS.

Patients should be offered open, laparoscopic and robotic radical prostatectomy, depending
on patient preference, after appropriate counseling, supplemented by information sheets.

In the event of an unrecordable PSA post-operatively there is no randomised evidence that
early post-operative RT offers advantage compared to early salvage RT.
Indications for referral to a Clinical Oncologist (outside of clinical trials) to discuss RT
includes a PSA which fails to become unrecordable or a rising PSA post-operatively. Salvage
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RT is most successful when the PSA is <0.2ng/ml (RFS 64%), however early referral for
discussion after one or two PSA rises is advised.

There is no randomized evidence for the use of androgen deprivation post-operatively
outside of clinical trials
3. Radioactive seed implantation – Brachytherapy
Patients may be considered with the following factors:





No greater than half the cores or sites (for TP biopsies) and <50% of biopsy material in
positive cores/sites
PSA <15 ug/l if Gleason 6 (3+3) and 10 ug/l if Gleason 7(3+4)
T1N0M0 or T2N0M0
Minimal lower urinary tract symptoms (LUTS) - IPSS < 12/35 / flow ≥15ml/s or IPSS <10 /
flow >10ml/s ()
Prostate volume ≤65ccm by MRI criteria.
Patient preference
o In patients with significant LUTS de-obstructing surgery prior to brachytherapy can
be considered after review in brachy centre
o Patients after TURP/HoLEP can be considered after review in brachy centre
Patients should be referred to the Specialist Multi-Disciplinary Team at Addenbrookes Hospital
4. External Beam Radiotherapy – EBRT
There are four RT centres in Anglia (Cambridge, Ipswich, Norfolk & Norwich and Peterborough).
All now have access to the advanced RT techniques of Intensity Modulated Radiotherapy (IMRT)
and Image-Guided Radiotherapy (IGRT). The verification protocols and planning target volumes
for radical treatments used are agreed by individual departments.
Criteria for patients undergoing EBRT







T1-3b N0 M0
Any Gleason grade
Life expectancy > 10 years in low/intermediate risk disease
Consider life expectancy > 5 years in high risk disease
No history of radio sensitivity or previous pelvic radiotherapy.
Contraindications to brachytherapy or radical prostatectomy.
Patient preference.
Radiotherapy and androgen deprivation therapy recommendations:
a) Radical radiotherapy without associated androgen deprivation therapy



pT1a/pT1c (10% sample volume) and Gleason <7 and PSA in normal range
Normal potency
Patient preference
b) Neoadjuvant (3-6 months) and concurrent androgen deprivation


pT1b/c-clinical T2a/b/c
Gleason < 8
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Anglia Cancer Network

Guidelines for the Management of Prostate Cancer
PSA < = 20 ug/l
c) Adjuvant androgen deprivation
Consider extending the period of androgen deprivation to 3 years for men with high risk localized
prostate cancer and discuss the benefits and risks of this option with them.
5. Watchful Waiting
This approach aims to avoid treatment or delay as long as possible. Consider in patients with
localized disease who have no symptoms and due to co-morbidities are unsuitable for radical
treatment options.
6. Long term androgen deprivation therapy alone
Patients who may reasonably be considered include:



Life expectancy less than 10 years.
Significant urinary symptoms may increase the advantages of offering androgen
deprivation.
No other significant risk factor for osteoporosis
Patient preference.
The options for androgen deprivation are:



LHRH agonists – goserelin, leuprorelin, triptorelin (intermittent therapy may be considered,
particularly for low volume minimal metastatic disease with a low PSA after 6 to 9 months of
treatment).
LHRH antagonists – degaralix (Limited indication according to local protocol)
Orchidectomy
Anti-androgen monotherapy therapy e.g. Bicalutamide, may be considered for selected
patients in whom active therapy is indicated but potency or the side-effects of LHRH
analogues are important issues.
Patients intending to pursue long term ADT (including adjuvant) should be considered for bone
densitometry at the start of their treatment and then at two yearly intervals. If bone density is < -2
or worse SD below the mean expected value, the patient should receive oral bisphosphonates and
calcium supplements as per the advice of the bone densitometry report. See Appendix 3.
Management options for locally advanced prostate cancer (without
metastases) T3b/T4 N0/1 M0



Androgen deprivation plus EBRT (T3/4 N0 M0)
Androgen deprivation alone
Watchful waiting (co-morbidity/patient preference)
Radical prostatectomy or brachytherapy are seldom appropriate for patients with stage cT3b
disease or more advanced disease.
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Management of Erectile Dysfunction Post Radical Treatments
Penile rehabilitation is defined as the use of any drug or device at or after radical
prostatectomy to maximize the recovery of erectile function. The purpose of penile
rehabilitation is the prevention of corpus cavernosum smooth muscle structural alterations, to limit
venous leak development during the period of recovery from neuropraxia, and therefore to
maximize the chances of a man returning to his preoperative level of erectile function.
Recent studies suggest a benefit from early pharmacological rehabilitation after radical
prostatectomy.
Proposed guideline :
a) Pre-op good Erectile function,( IIEF >16/25), Good unilateral / bilateral nerve spare:

Cialis (tadalfil) 5mg Once Daily (preferred treatment)

Review in 3 months if no early response, consider change to MUSE/ Intracavernosal
Injection alprostadil / Vacuum tumescence device.

Consider continuing any PDE5 after 3 months as return of normal erections can be delayed
up to 24 months
Consider use of Vacuum device in combination with PDE5
If at 3 months review there is early response to PDE5 – Cialis or Sildenafil then change over to
PRN dose
b) Pre-op ED or IIEF <16/25 or poor nerve spare:

Direct MUSE/ Intracavernosal Injection alprostadil / Vacuum tumescence device.
There is less evidence for management of ED post radiotherapy. However the above should still
be considered to offer potential benefit and has been recommended by NICE guidance (2014).
Men should be provided with early and ongoing access to specialist erectile dysfunction services
including psychosexual counseling.
Androgen deprivation therapy and erectile dysfunction
NICE guidance (2014) recommends that men should be offered access to specialist erectile
dysfunction services including psychosexual counseling as well as treatment with PDE5 inhibitors
for loss of erectile function on hormone treatments.
Department of Health Guidance
DoH guidance(5) (HSC1999/148) on treatment of erectile dysfunction states:
“the Department advises doctors that one treatment a week will be appropriate for most patients
treated for erectile dysfunction. If the GP in exercising his clinical judgement considers that more than
one treatment a week is appropriate he should prescribe
that amount on the NHS.”
Salvage Therapy for Recurrent Prostate Cancer Post-Radiotherapy
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Guidelines for the Management of Prostate Cancer
In the event of biochemical recurrence after EBRT, salvage therapy may be considered. Local
salvage local therapies (includes prostatectomy, cryotherapy, HIFU & HDR brachytherapy) are
associated with clinically significant toxicity and counseling of the patient is essential. There are no
randomized clinical trials comparing outcomes with observation, but a systematic review showed
similar biochemical recurrences but differing toxicities between options.
There are no formal criteria established to determine who will benefit most from salvage therapy,
however the following parameters may predict poorer outcome




High risk disease at time of original diagnosis
Short time interval to biochemical relapse (< 18 months)
Short PSA Doubling time (<8 months)
A serum PSA > 10 ng/ml at time of salvage consideration
Referral to a centre of expertise in salvage options and use of clinical trials is recommended. Local
imaging to establish no evidence of nodal or bone disease should be performed. Additional
imaging may be undertaken at referral centres (eg whole body MRI, Choline-PET) before
embarking on salvage therapy.
Egs
Mount Vernon Hospital HDR Brachytherapy (Prof Peter Hoskins)
UCL London HIFU (Prof Mark Emberton)
Guildford Cryotherapy (Mr John Davies)
Management Options for Metastatic Disease
Local therapies for the prostate depend on the symptoms, extent of disease (locally and
metastatic) and the performance status of the patient. Assessing the symptomatic response to
hormone therapy is the usual course but palliative TURP or radiotherapy may well be appropriate
(Radical prostatectomy or brachytherapy are not considered).
Treatment of systemic disease depends on the existing therapies at the time of metastatic
development and the individual circumstances of the patient.
Castration Sensitive Metastatic Prostate Cancer
The gold standard (outside of clinical trials) for first line treatment is an LHRH agonist with antiandrogen given initially to prevent disease flare. Although androgen deprivation therapy (ADT) is
palliative, it can normalize serum levels of prostate specific antigen (PSA) in over 90% of patients
and can produce objective tumor responses in 80-90%. This antitumor activity can improve quality
of life (QOL) by reducing bone pain as well as the rates of complications (eg, pathologic fracture,
spinal cord compression, ureteral obstruction).
The duration of response to ADT for patients with metastatic disease is highly variable, and most
prostate cancer patients eventually experience disease progression despite treatment. Patients
who have progressed while on ADT are said to have castration resistant disease, although such
tumors may remain responsive to additional therapies directed against androgenic stimulation of
the prostate cancer.
Castration Resistant Metastatic Prostate Cancer (CRPC)
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Patients should remain on ADT despite rising PSA. The use of additional treatments should be
considered on the basis of symptoms, DT PSA, and an individual patients co-morbidities rather
than asymptomatic PSA change alone. Referral/discussion with Oncologists (if followed up in
Urology Clinics until this point) should be considered.
At the time of writing there is no evidence/consensus regarding the sequencing of both older and
newer therapies in the CRPC setting. The availability of funding (CDF/NICE approval) for newer
therapies remains under review.
‘Older Endocrine Options’
Maximum androgen blockage Bicalutamide 50mg od
Antiandrogen withdrawal (~20% men progressing on MAB will have PSA/symptomatic response to
withdrawal of antiandrogen)
Glucocorticoids eg prednisolone 10mg od, Dexamethasone 0.5mg od
Diethylstilboestrol 1mg od (+aspirin)
‘Newer Endocrine and Chemotherapy Options’
Table from NHS England draft document
An algorithm for possible sequencing is listed in Appendix 6
Therapy for painful bone metastases
External beam radiotherapy remains treatment of choice for painful bone metastases. A
single 8Gy fraction is recommended unless considering scenarios of re-treatment/spinal
cord compression.
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
Radium 223 is now available (Sept 2014) via CDF application and administered via Nuclear
Medicine Dept. It is indicated in CRPC post-docetaxol for symptomatic bone metastases
with no visceral metastases.




Strontium 89
Surgical decompression
Internal fixation
Bisphosphonates
Other Considerations


Consider bilateral breast bud irradiation in patients with CRPC prior to commencement of
diethystilboestrol to minimize development of tender gynaecomastia. It is not effective for
established gynaecomastia.
Cyproterone acetate 50–100 mg od is useful to treat the hot flushes associated with LHRH
analogue. As monotherapy there is a risk of liver damage and it is less effective than LHRH
analogue.
Small cell carcinoma
If patient has pure small cell carcinoma of the prostate serum levels of PSA do not correlate with
disease activity. Some patients may have combination of small cell and adenocarcinoma where
ADT may also be required. Exclude a small cell tumour of the bladder with prostatic infiltration.
Localised disease – initial treatment is with ‘small cell’ chemotherapy eg Carboplatin/Etoposide EP
or Cyclophosphamide, Doxorubicin, Vincristine (CAV) followed by radiotherapy to a dose of
55Gy/20 fractions over four weeks.
Metastatic disease at presentation chemotherapy alone is more appropriate unless there is
concern regarding the risk of uncontrolled local progression when a palliative radiotherapy
treatment schedule to the prostate can be offered.
.
Follow up
Follow up arrangements have been determined at each hospital in conjunction with primary care
trusts.
If the condition is stable, consider referral back to Primary Care.
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PSA Guidance for General Practitioners
Nk Two Week referral for suspected prostate cancer
1.
2.
An elevated age specific PSA* in men with a 10 year life expectancy
A high PSA (>20ng/mL) in men with a clinically malignant prostate or bone pain
(*if the PSA is marginally elevated, a second PSA, two weeks later, may be helpful before referral)
*Age Specific PSA (NICE Guidelines 2005)
Age 50 to 59 years
PSA ≤ 3 ng/mL
Age 60 to 69 years
PSA ≤ 4 ng/mL
Age 70 years or older
PSA ≤ 5 ng/mL
Risk Stratification of Prostate Cancer (at diagnosis)
Level of risk
PSA (ng/mL)
Gleason score
Stage
Low risk
<10
and
≤6
and
T1-T2a
Intermediate risk
10-20
or
7
or
T2b
High risk
>20
or
8-10
or
≥T2c or N+ or M+
T1: not palpable; T2a: organ confined, < 50% of 1 lobe; T2b: organ confined, >50% of 1 lobe; T2c: organ confined, both lobes; T3a/b: through capsule/ into seminal vesicles;
PSA follow up during Active Surveillance (for patients who are candidates for treatment with curative intent if disease progresses)
Criteria for Discharge
Primary Care follow up
Trigger for Re-referral
• Secondary care follow-up
• Not applicable
• Not applicable
PSA follow up after Radical Prostatectomy
Criteria for Discharge
Primary Care follow up
Trigger for Re-referral
• PSA <0.1ng/mL
• Low risk: six monthly PSA for five years
then annually for five years
• PSA ≥ 0.2ng/mL
• Intermediate/High risk: six monthly PSA
for ten years
• 2 consecutive rises above 0.02ng/mL
• Asymptomatic
(for patients managed with
1
standard PSA test)
1
(for patients managed with super-sensitive PSA
test)
• Symptomatic
1
Costs: standard PSA = £6.29; super-sensitive PSA = £28.02. Source: NNUH Feb 2015
PSA follow up after Radical Radiotherapy/Brachytherapy
Criteria for Discharge
Primary Care follow up
Trigger for Re-referral
• PSA < 2ng/mL or stable PSA
• Six monthly PSA for five years
• Asymptomatic
• Annual PSA year 6 onwards
• PSA > 2ng/mL above nadir (the “nadir” is
the lowest recorded PSA since diagnosis)
Intermediate and high risk patients may
remain under secondary care follow-up until
off hormones
Intermediate and high risk patients may need
extended adjuvant hormone treatment for up to
three years as recommended on letter to GP
• Symptomatic (LUTS or rectal symptoms)
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PSA follow up for patients on Hormone Treatment
Criteria for Discharge
Primary Care follow up
Trigger for Re-referral
• PSA <10ng/mL or stable PSA
• Six monthly PSA
• *PSA >10ng/mL
• Asymptomatic
• Symptomatic
*Unless PSA threshold for re-referral has been
stated by the urologist
If PSA rising, consider starting bicalutamide 50mg
once daily in addition to LHRH analogues
PSA follow up for patients on Watchful Waiting (in men >80 years of age or with a life expectancy of less than 10 years)
Criteria for Discharge
• PSA <20ng/mL or stable PSA
• Asymptomatic
Primary Care Follow Up
• Six monthly PSA for five years then
annually if deemed appropriate
Trigger for Referral to Urology
• *PSA >20ng/mL
• Symptomatic
*Unless PSA threshold for re-referral has been
stated by the urologist
Persistently raised PSA after normal biopsies (incl HGPIN) or with stable serial PSA
Men with a life expectancy of greater than 10 years
Criteria for Discharge
Primary Care follow up
Trigger for Re-referral
• Normal biopsy with a stable PSA
• Six monthly PSA
• Increase in PSA of 25% in 6 months or
50% in 12 months (i.e. a PSA doubling
time of <2 years)
• Asymptomatic
• 2 consecutive rises
• the PSA threshold for re-referral may
be stated by the urologist
Men with a life expectancy of less than 10 years
Criteria for Discharge
Primary Care follow up
Trigger for Re-referral
• Normal biopsy with a stable PSA
• Six monthly PSA for five years
• PSA >20ng/mL
• Asymptomatic
• Annual PSA year 6 onwards
• Symptomatic
If PSA > 20ng/ml at referral to GP, the PSA
threshold for re-referral should be stated by the
urologist
THIS IS A GUIDELINE ONLY
INDIVIDUALISE YOUR FOLLOW-UP SCHEDULES ACCORDING TO EACH PATIENT’S CIRCUMSTANCES
As a patient ages or their co-morbidities change, their treatment group should be adjusted accordingly. For example, a patient
who underwent a radical prostatectomy at the age of 69 years, who is found to have a PSA recurrence at age 81 years, would
probably be best managed with watchful waiting.
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Appendices
Appendix 1
Prostate Histology, grading
Appendix 2
Staging
Appendix 3
Osteoporosis Guidelines
Appendix 4
Clinical Trials supported by the network
Appendix 5
Prostate Cancer Pathway (14-1C-113g)
Appendix 6
Draft National Chemotherapy Algorithm
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Appendix 1 – Prostate histology, grading
 Gleason Score
Grading systems have been shown to correlate with tumour stage, incidence of seminal vesicle
and lymph node involvement, occurrence of distant metastases and survival. However, the
reproducibility of such systems is not perfect and there is considerable intra- and inter-pathologist
variability (Gallee et al, 1990)
The histological grading system most commonly used is that described by Gleason (Gleason et al,
1974) and is given on adenocarcinoma and its variants.
Unlike other grading systems, emphasis is placed on the assessment of the architectural growth
pattern and degree of glandular differentiation, rather than cytological features, thus enabling
grading to be performed at low or medium power magnification. Five tumour grades 1-5 are
recognised (with sub-divisions to form 9 originally described patterns), forming a continuous
spectrum of appearances from grade 1 being the well differentiated to grade 5, the most poorly
differentiated. A simplified description of the histological appearances is given here:
Gleason Grading of Prostate Cancer – summary of histological appearances:
 Grade 1 Uniform closely packed separate glands forming a circumscribed nodule
 Grade 2 Slightly less uniform, separate glands, more loosely packed, with a partially
circumscribed margin
 Grade 3 Single separate infiltrating often angulated glands (3A), very small infiltrating glands
(3B) or circumscribed cribriform or papillary masses (3C)
 Grade 4 Fused raggedly infiltrating glands (4A), which may also consist of large pale cells
‘hypernephroid’ cells (4B)
 Grade 5 Solid rounded masses with necrosis (5A) or ragged infiltrating tumour (5B)
The majority of tumours do not have a uniform appearance, therefore the primary grade is
assigned to the pattern which is predominant, and the secondary grade to the next most frequent.
The Gleason score is the sum of the primary and secondary grades, unless only one tumour grade
is represented, when the score is then simply the grade doubled. This gives a Gleason score
range of 2-10. If a third less frequent grade is present, this is the tertiary grade and should be
clearly reported if this is of higher grade than the primary and secondary grades. Modifications to
the scoring system to incorporate higher grades into the Gleason score have been proposed for
needle biopsy reports (e.g. Pan et al, 2000) because of the worse prognosis conferred by the
presence of poorly differentiated elements. If a ‘modified’ method of Gleason score is used (i.e.
including the tertiary higher grade element in the score), this should be clear from the text of the
report. ‘Modified’ scores are not used in reporting radical prostatectomy specimens.
A Gleason grade should be assigned, even for small tumour foci. However, Gleason grading of
tumours showing therapy related changes is not possible, unless sufficient areas can be identified
within the tumour which do not show these artefacts.
Gleason scores of less than 5 are not usually made in assessing needle core biopsies, since
entire tumour nodules are not represented in the fine cores. For biopsies from different sites, the
Gleason scores at those sites should be stated.
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Appendix 2 - Staging
TNM Classification of Prostate Cancer (TNM 2002 edition)
TO
TX
No evidence of primary tumour
Primary tumour cannot be assessed
T1
Clinically unapparent tumour, impalpable and not visible by imaging
T1a Tumour an incidental finding in <5% of resected tissue
T1b Tumour an incidental finding in > 5% of resected tissue
T1c Tumour identified by needle biopsy (e.g. because of raised PSA)
T2
Tumour confined within prostate
T2a Tumour involves < half one lobe
T2b Tumour involves > half a lobe but not both lobes
T2c Tumour involves both lobes
T3
Tumour extends through the prostate capsule
T3a Unilateral or bilateral extracapsular extension
T3b Tumour invades seminal vesicle(s)
T4
Tumour is fixed or invades adjacent structures – i.e. bladder neck, external sphincter or
rectum, levator muscles or fixed to pelvic side wall
Regional Lymph Nodes
NX
Nodes cannot be assessed
N0
No regional lymph node metastases
N1
Regional lymph node metastasis
Distant Metastases
MX Distant metastasis cannot be assessed
M0
No distant metastasis
M1
Metastasis
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Appendix 3 – Osteoporosis Guidelines
GUIDELINES FOR THE PREVENTION AND MANAGEMENT OF OSTEOPOROSIS IN
PATIENTS WITH PROSTATE CANCER EXPECTED TO RECEIVE PROLONGED ANDROGEN
DEPRIVATION. Dr Helen Patterson, Professor Juliet Compston.
This recommendation relates to patients on:
1. Indefinite LHRH analogue therapy or
2. Three years of adjuvant androgen deprivation following radical radiotherapy.
Bone densitometry (hip and lumbar spine) should be requested at the time the decision to initiate
LHRH analogue therapy is made and at 2 yearly intervals if androgen deprivation therapy is
continued if initial densitometry satisfactory.
If the T score is -2 or worse at initiation of LHRH analogues then patients should commence
treatment with oral bisphosphonates e.g. Alendronate 70mg po once weekly or Risedronate 35mg
po once weekly with calcium and vitamin D supplementation eg Adcal-D3 one tablet b.d.,
Calcichew D3 forte one b.d. or Calcit D3 one b.d. A repeat DEXA scan should be repeated at 5
years to reassess the need for continued bisphosphonate and supplement treatment.
If the T score is -2 or worse perform lateral thoracic and lateral lumbar spine films to exclude a
pre-existing crush vertebral fracture as 2/3 do not come to medical attention, and patients who
experience a vertebral fracture have a 20% incidence of a further fracture over the ensuing 12
months. If a fracture is identified, commence treatment as above with oral bisphosphonates,
calcium and vitamin D.
If the T score is between -1 and -2 patients should have repeat densitometry at 2 years and
thereafter every 2 years and if higher than -1 repeat at 3 years to monitor progress.
In addition, any patient considered to be at increased risk (see below) of osteoporosis, prior to the
commencement of LHRH analogue therapy, should also be considered for bisphosphonate
therapy.
Past history of fragility fracture.
Concurrent corticosteroid therapy.
Low body mass index <19kg/m2.
Heavy smoking.
High alcohol intake.
There are national guidelines which state that anyone over the age of 65 years started on any
dose of oral corticosteroid expected to be continued for more than 3 months should be offered oral
prophylaxis against osteoporosis with a bisphosphonate, either Alendronate 70mg once weekly or
Risedronate 35mg once weekly together with calcium and vitamin D supplementation as above.
Patients expected to undergo short-term LHRH analogue therapy (neo-adjuvant and concurrent
with radical radiotherapy alone) do not need to undergo routine bone densitometry.
For patients who are on treatment for known osteoporosis, LHRH analogue therapy should still be
considered the treatment of choice to accompany their radical radiotherapy treatment unless other
issues indicate the use of bicalutamide.
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Appendix 4 - Clinical Trials
The Manual for Cancer Services 2004 (updated 2011/12) states that one of the responsibilities of
the MDT Lead Clinician is ‘To ensure mechanisms are in place to support entry of eligible patients
into clinical trials…’. The infrastructure to support clinical trials activity within the Anglia is the
responsibility of the newly formed Clinical Research Network: Eastern (1st April 2014). Division 1
of this network will focus on Cancer and replaces the previous West Anglia Cancer Research
Network (WACRN) and Anglia East Cancer Research Network (AECRN). In addition, the footprint
of the new CRN Eastern also includes Colchester in Essex and East/North Herts Trusts in Herts &
Beds.
For further details, please contact:
Kath Jones (Research & Development), Clinical Research Network: Eastern.
Norfolk and Norwich University Hospital, ([email protected])
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Anglia Cancer Network
Guidelines for the Management of Prostate Cancer
Appendix 5 – Prostate Cancer Pathway (14-1C-113g)
PROSTATE CANCER PATHWAY (E&W) Final
Other Referrals
i.e. non urgent 18ww
referral
Tertiary Referrals
Active
Monitoring
SPECIALIST
MULTIDISCIPLINARY
(SMDT) MEETING
OPA
Decision to
treat (DTT)
Recurrence detected
Brachytherapy
Cryotherapy
Urgent GP
suspected
cancer referral
(2WW)
Prostate Clinic
with biopsy
LOCAL
MULTIDISCIPLINARY
TEAM (LMDT) MEETING
Histology discussed.
Staging investigations
requested, if appropriate.
RRP
Patient informed of
diagnosis
(OPA / telephone)
- Decision to treat (DTT)
- Patient referred to SMDT if
appropriate (i.e. if patient
chooses brachytherapy/
surgery)
L/SMDT /
OPA
to assess
fitness for
subsequent
treatment
Radiotherapy
+/- Androgen
Deprivation
Therapy (ADT)
Staging
MRI / Bone/CT
LMDT
MEETING
Earliest
clinically
appropriate
date, decision to
treat (DTT)
ADT
Adjuvant
Radiotherapy
Palliative Care
Androgen
Deprivation
Therapy (ADT)
Active
Monitoring
Consultant upgrade points
e.g. referral meets NICE criteria; at first seen,
during or after diagnostic tests; on or before
MDT date & decision to treat date +62 days
from these upgrade point dates
Palliative Care
Consider Clinical Trial and Follow Up
Referral to extended MDT services at any point in pathway e.g. Palliative care specialists, Specialist Nurses and AHPs, education about adverse effects of treatment; access to help and advice from all specialists; staff alert to psychosocial needs;
therapists/local healthcare teams, Community Matron, Pharmacists (medicines usage review), Social Services, Mental Health Services, Housing benefits (Social Care and other agencies), GPs, Expert Patient Programme, Smoking Cessation, Alcohol
Service (NORCAS), Voluntary organisations, information on prescription, Homeshield (over 60s)
Day 0
(Referral)
Key:
By Day 14
(1st seen)
Unit /
Centre
Centre
Access to specialist
services
By Day 28
(LMDT meeting)
GFOCW
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INTERIM
By Day 42
(DTT)
Day 0
(DTT)
By Day 62
(treatment)
Elapsed time for follow up or presentation of recurrence,
mets or predetermined gap between treatments
Updated, Approved and Published: May 2014
By Day 31
(2nd treatment)
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