Download Guidlelines for the Management of Urological

MERSEYSIDE AND CHESHIRE CANCER
NETWORK: GUIDELINES FOR THE
MANAGEMENT OF UROLOGICAL
CANCER
Testicular Tumour Treatment Guidelines
Authors:
Professor Peter Clark
Dr Judith Carser
Mr Mark Fordham
Review Date:
August 2013
Testicular Guidelines
Review Date: August 2013
CONTENTS
1.
2.
3.
4.
5.
5.1
5.2
5.3
5.4
5.5
5.6
5.7
5.8
5.9
5.10
5.11
5.12
5.13
5.14
5.15
5.16
6.
6.1
6.2
6.3
6.4
6.5
7.
8.
8.1
8.2
9.
10.
10.1
10.2
10.3
10.4
10.5
11.
12.
13.
14.
Introduction
Details of the Testis MDT
GP referral guidelines
Initial management of a suspected testicular tumour and
local MDT referral guidelines
Pathology guidelines
Clinical Information Required on the Specimen Request Form
Preparation of Specimens before Dissection
Specimen Handling and Block Selection
Gross Examination of Orchidectomy Specimens
Primary Lymphadenectomy Specimens
Excision of Residual Masses after Chemotherapy
Block Selection
Orchidectomy Specimens for Clinically Localised Disease
Retroperitoneal Lymph Node Dissections and Postchemotherapy Residual Masses
Classification of Testicular Tumours
Pathological Prognostic Factors in Stage 1 Disease
Metastatic Disease and Post-chemotherapy Residual Masses
Reporting of Biopsy Specimens
Macroscopic Items
Microscopic Items
Reporting of Frozen Sections
Radiology guidelines
Clinical background
Who Should be Managed?
Recommendations for Cross-Sectional Imaging in Cancer
Management August 2006
Staging Objectives
Staging Nodal and Metastatic Disease
Guidelines on Fertility Support Services
Treatment protocols
Seminoma
NSGCT
Pre-chemotherapy preparation of the patient
Follow up protocols
Stage 1 seminoma
Metastatic seminoma
Stage 1 NSGCT
Metastatic NSCGT
Management of residual masses post chemotherapy
Management of Metachronous Contralateral Testis
Tumour
Specialist Palliative Care
Clinical Trials
Patient Information
Page
4
5
5
5-6
6-11
6-7
7
7
7-8
8
8
8
8
8-9
9
9-10
10
10-11
11
11
11
11-12
11
11
11
12
12
13
14-16
14-15
15-16
17
18-22
18-19
19
19-20
20
21-22
22
22
23
24
2
APPENDICES
Appendix A - Pathway
Appendix B - Histology: Handling and Cut-up of Surgical
Specimens
Appendix C - TNM Pathological Staging
Appendix D - Treatment Algorithm
Appendix E – Chemotherapy protocols
25
26-29
REFERENCES
34-38
30
31
32-33
3
1.
INTRODUCTION
The majority of solid neoplasms that develop within the testis are malignant of which
95% are germ cell tumours (GCT). These GCTs are classified by their histological
appearance into seminoma (60% - 70% incidence; age range 20 – 50 years) and nonseminomatous germ cell tumours (NSGCTs), which in the UK are often referred to as
teratomas, (incidence 30% - 40%; age range 15 – 40 years). Those tumours with mixed
elements (15%- 30%) are managed as for NSGCTs. This histological classification
correlates well with the natural history of the tumour types and also their response rates
to modern treatment modalities. Seminoma is radiosensitive but both seminoma and
NSGCT respond well to cisplatin based chemotherapy regimens with 5 year survival
rates of 90% for all GCTs and >95% for all seminomas. Prognosis is most favourable in
low volume disease with a 99% 5 year survival rate for all stage I tumours but less
favourable (~60%) for the rarer cases of advanced tumours with visceral metastases.
Although testicular tumours are rare with an incidence of about 3/100,000 in the UK and
account for only 1% of all male cancers, it is the commonest solid malignancy in men in
the age range 15 – 35 years and incidence is increasing.
In Mersey and Cheshire Cancer Network approximately 80 - 90 new tumours are
diagnosed each year. No specific aetiological factors have been identified but there is
an increased relative risk in first degree relatives (father/brother) (1) in patients with a
history of testicular maldescent (2) and patients with primary infertility (3). In addition,
men who have been successfully treated for testis cancer have a 2% - 5% incidence of
developing a further tumour in the remaining testis, in some cases many years later (4).
The remaining 5% non-germ cell tumours comprise mainly lymphoma presenting in adult
men (age range 50 – 70 years); other tumours include sex cord tumours (sertoli cell
tumours, leydig cell tumours) in adults and paratesticular tumours (rhabdomyosarcoma
in infants and leiomyosarcoma in adults).
A particular feature of some GCTs is the presence of the serum tumour markers beta
Human Chorionic Gonadotrophin (bHCG), alpha feto-protein (AFP), and lactate
dehydrogenase (LDH). Although not uniquely specific for GCT, they provide important
information when they are present about tumour burden, tumour type and response to
treatment and possible relapse. The presence of a raised serum AFP indicates a
teratomatous element within the tumour even if this is not identified on histology.
Although bHCG may be moderately raised in seminoma, high values are associated with
NSGCT and indicate tumour burden and activity. The serum marker LDH is non specific
but can indicate tumour burden and be a sign of tumour relapse. The post-orchidectomy
rate of fall of bHCG (half-life 2-3 days) and AFP (half-life 5-7 days) will indicate if the
tumour has been removed or if metastases are present. Because most patients
presenting with a testicular tumour are young adults often at the stage of considering
starting a family, the potential effects on their fertility of both surgery and chemotherapy
need to inform the planning of any management regime.
These guidelines should be read in conjunction with the European Association of
Urology Guidelines (2011), the European Society of Medical Oncology Clinical
Recommendations (2010) and the National Comprehensive Cancer Network Guidelines
(2011) (5-8).
4
2.
DETAILS OF THE TESTIS MDT
Core members:
Peter Clark
Judith Carser
Doug Errington
Mark Fordham
Vijay Aachi
Jane Belfield
Iwan Lewis-Jones
Nicola Wilson
Carmela Parisi / Claire Richards
Consultant Medical Oncologist
Consultant Medical Oncologist
Consultant Clinical Oncologist
Consultant Urological Surgeon
Consultant Histopathologist
Consultant Radiologist
Consultant Andrologist
Clinical Nurse Specialist
MDT Coordinators
This group meets every Thursday at 8.30am before the testis tumour clinic.
Extended members who are available when needed are:Doug Errington
Iwan Lewis-Jones
Richard Page
Professor J Vora
Consultant Clinical Oncologist
Consultant Andrologist
Consultant Thoracic Surgeon
Consultant Endocrinologist
The Network Pathway for testicular tumours is outlined in Appendix A.
3.
GP REFERRAL GUIDELINES
A fast track fax referral form is available to GPs for all patients with suspected testicular
tumour and all patients are seen urgently. GPs have the facility to request scrotal
ultrasound scan and tumour marker estimation.
4.
INITIAL MANAGEMENT OF A SUSPECTED TESTICULAR TUMOUR AND
LOCAL MDT REFERRAL GUIDELINES
In the majority of cases, when the intra-testicular mass has been confirmed,
management consists of a radical orchidectomy performed via the groin and dividing and
transfixing the spermatic cord at the deep inguinal ring. The patient is counselled that
the operation is being performed to remove what is suspected to be a malignant tumour
but this will not be confirmed until the testis has been examined histologically (unless the
tumour markers are raised or there is evidence of metastatic disease). As part of the
pre-operative preparation it is essential for serum tumour markers to be measured. If
elevated, then sequential post-operative measurements will indicate whether they fall to
normal, indicating a stage I tumour that has been completely removed, or if they remain
elevated indicating metastatic disease even if the CT scan is normal. Some men will
express anxiety at the change in their body image when an orchidectomy is discussed.
The use of a silicone testicular implant placed at the time of the surgery produces a
satisfactory prosthesis in most patients but some find that there is an unnatural feel or
appearance which they can find difficult to accept. All men should have the option of
having a prosthesis inserted at the time of radical orchidectomy.
In the rare cases where a patient presents with a testicular tumour in a solitary testis, or
if sub fertility is suspected, sperm banking should be offered before any surgery is
5
performed and in the former case, to consider performing a testis sparing excision of the
tumour. Although testis sparing surgery runs the risk of incompletely removing any
tumour, there is evidence to suggest that in some cases chemotherapy may eradicate
any remaining malignant cells within the testis (9, 10). Such patients can be referred to
the specialist MDT for further assessment. In cases where the patient has presented
with advanced GCT and extensive distant metastases, surgery for the primary may be
regarded of secondary importance to commencing urgent chemotherapy treatment (11).
In cases of patients with heavy tumour burden and high tumour markers it is important to
exclude cerebral metastases as neurosurgical treatment may be indicated prior to
starting chemotherapy. These patients should be referred urgently to Professor P. Clark
or Dr J. Carser at Clatterbridge Centre for Oncology.
Following orchidectomy, the patient should be referred directly to Professor P. Clark or
Dr J. Carser where the patient will be seen in the next weekly clinic or on an ad hoc
basis if assessment is urgently required. The Specialist MDT co-ordinator contacts the
local pathologist who will inform Dr Aachi and send the slides or tissue for review. The
histopathology is then discussed in the next Testis MDT. Any radiology will be amended
by Dr Belfield or arranged subsequently at the RLBUHT and reviewed by Dr Belfield.
Patient presents with Testis Tumour
If too ill – Peter Clark/Judith Carser
(PIC/JEC)
IMMEDIATELY
If physically fit – pre-op markers
Radical Orchidectomy
Advice about body image & Testis
Prosthesis
Within 24 hours
Refer directly to PIC/JEC
Post op markers
Key:
Local Urology Team
5.
Histology and radiology reviewed
for SMDT
PATHOLOGY GUIDELINES
Histopathological examination of the radical orchidectomy specimen assesses the
primary for both the type of testicular tumour, evidence of lymphovascular invasion and
the extent of spread of the tumour within the scrotum ie the pT stage. Where a tumour
exhibits both seminoma and teratoma elements the tumour is managed according to the
teratoma element. The presence of differentiated teratoma is also noted.
5.1
Clinical Information Required On The Specimen Request Form
This includes laterality, the type of specimen (biopsy, simple or radical orchidectomy,
lymphadenectomy or post-chemotherapy residual mass), the anatomical origin of lymph
6
nodes and 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.
Pathology specimens should be dissected and reported in accordance with the latest
dataset for testicular tumours and post chemotherapy residual masses reports
published by the Royal College of Pathologists. Standards and datasets can be
found at www.rcpath.org.uk
5.2
Preparation of Specimens before Dissection
Orchidectomy and lymphadenectomy specimens generally require fixation in formalin for
24 hours at least. Fixative can be slow to penetrate the thick testicular coverings, and
therefore careful incision into the capsule can be useful for tumour preservation. It
should be noted that ‘bivalving’ of the fresh specimen can lead to bulging of the cut
surfaces and the distortion can make assessment of the relationship between the tumour
and the rete and tunica difficult. Because germ cell tumours are particularly poorly
cohesive, there may also be artifactual contamination of relevant resection margins. This
spread of tumour can also mimic vascular invasion.
5.3
Specimen Handling and Block Selection
A synoptic reporting proforma has been added as an aide memoire for the main features
of these neoplasms (Appendix B). The proforma extracts the dataset currently used in
diagnosis and staging. This would usually be supplemented by a more detailed written
report. Aspects of best practice in handling testicular tumour specimens have recently
been reviewed (12).
5.4
Gross Examination of Orchidectomy Specimens
Most patients with a clinical diagnosis of testicular tumour undergo a radical
orchidectomy, whereby the testis is removed with the tunica, epididymis and a length of
spermatic cord via an inguinal approach. Organ-sparing surgery, to preserve a degree of
natural hormonal production, is an option in specific cases, for instance in patients with
bilateral testicular tumours (13). Excision margins are inked in these cases. 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 measured 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 midpoint and the base
of cord 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 well represented in tissue sections
as it separates from the testis. The absence of invasion should therefore be recorded at
7
this time for staging purposes. Breaches in the tunica are also noted. The specimen can
then be bivalved through the rete and epididymis.
In summary, the following are noted:
 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 testis, epididymis
and cord
 The presence of abnormalities in the residual normal testis.
5.5
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 the UK.
Any such specimens are measured in three dimensions. Lymph nodes are identified and
described as either macroscopically normal or involved by tumour.
5.6
Excision of Residual Masses after Chemotherapy
A complete retroperitoneal lymph node dissection may be performed in these cases but
often only the involved lymph nodes are removed (‘lumpectomy’). Specimens are
measured in three dimensions. It is useful to ink the surgical resection margins as
completeness of excision is a determinant of outcome. The masses usually consist of
single or multiple lymph nodes but occasionally visceral metastases may be resected.
5.7
Block Selection
Comprehensive sampling is essential for both primary resections and residual masses
as the identification of even small areas of a different subtype can alter patient
management and impact on prognosis. Although the recommendation of one block per
centimetre of tumour is usual, more may be required to adequately represent all the
macroscopically different areas of tumour as well as the interface with surrounding
structures for staging and management purposes. Conversely, large but homogeneous
tumours may require less.
5.8
Orchidectomy Specimens for Clinically Localised Disease
Blocks are selected to represent:
•
The cord resection margin, midpoint and base of cord at least (prior to
sectioning the tumour to avoid contamination)
•
The relationship of the tumour(s) to the rete testis, 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.
8
5.9
Retroperitoneal Lymph
Residual Masses
Node
Dissections
and
Post-chemotherapy
Blocks are selected to represent:
•
All areas of the positive node(s) with different macroscopic appearances
(solid, cystic, pale or haemorrhagic)
•
The minimum distance of the tumour to the nearest inked resection
margin
•
All macroscopically negative nodes to search for micrometastatic disease.
For post-chemotherapy residual masses, particularly in the absence of a biopsy
diagnosis prior to treatment, it is often useful to include areas of necrosis as ghost
outlines of the tumour often remain and allow the distinction between seminoma and
teratoma.
5.10
Classification of Testicular Tumours
There are two major classifications of germ cell tumours, the British Testicular Tumour
Panel (BTTP) (14-16) and the World Health Organization (WHO) (17) The BTTP
classification was based on a review of over 1000 cases with clinical outcome, prior to
the introduction of platinum based therapy. Whereas the WHO classification lists tumour
subtypes individually, the BTTP tends to group different patterns of differentiation into
categories that were clinically relevant at the time. The BTTP approach led to the early
recognition of the malignant potential of testicular tumours entirely composed of
differentiated, somatic elements in the adult male (16) and the use of teratoma
differentiated rather than mature teratoma to distinguish them from their ovarian
counterparts, which are essentially benign. The malignant nature of these tumours in
adult (18, 19) but not prepubertal males (20, 21) was subsequently confirmed.
Unfortunately, the category of teratoma in the WHO classification contains both benign
and malignant tumours. Dermoid cysts are classified as teratomas, yet are considered
to be benign (17, 22), although only a very small number of malignant cases have been
reported. It is essential for clinical management purposes that it is clear that tumours
composed entirely of differentiated somatic elements can metastasise and the term of
teratoma differentiated appears to convey that understanding. Furthermore, these
tumours are refractory to germ cell type chemotherapy, and can undergo secondary
transformation towards a somatic malignancy. This was only clearly recognised and
characterised relatively recently (23) and was not described in the BTTP classification.
Equally, the BTTP only catalogued trophoblastic tumours with a biphasic pattern
equivalent to choriocarcinoma. The few cases of cystic trophoblastic tumour were
described subsequently, usually in post-chemotherapy residual masses, and they
appear to be associated with good prognosis (24, 25). Placental site trophoblastic
tumours are even rarer (26, 27). Correlations between the major categories of BTTP and
the WHO classifications are easy to draw.
5.11
Pathological Prognostic Factors in Stage I Disease
For classical seminomas, tumour size (up to 40 mm versus over 40 mm), invasion of the
rete testis and vascular invasion (lymphatic and/or venous) have been identified as risk
factors for relapse and are used in some centres to identify patients who may benefit
from adjuvant treatment rather than surveillance (28, 29). Invasion into the rete testis
9
was defined as direct spread into the stroma of the rete testis and not tubular
involvement (pagetoid spread of intratubular germ cell neoplasia or luminal invasion) in
the pooled analysis of large surveillance studies (28). It should be emphasised that the
assessment of vascular invasion can be particularly difficult in seminomas due to the
extremely friable nature of the tumour, hence the need for careful handling as
emphasised earlier.
For teratomas/nonseminomatous germ cell tumours, vascular invasion (lymphatic and/or
venous) has consistently been identified as a risk factor and is used to guide
management (30-33). The presence and extent of undifferentiated teratoma has also
been shown to be predictive, but not always on multivariate analysis (32, 33). In
teratoma differentiated, the presence of immature elements is not a prognostic factor but
the development of secondary malignant transformation, characterised by an invasive
growth pattern, is associated with poor prognosis unless complete surgical excision is
achievable (23).
5.12
Metastatic Disease and Post-chemotherapy Residual Masses
The role of pathology in metastatic disease is to confirm the diagnosis of a germ cell
tumour if there is clinical uncertainty. However, prognosis and treatment decisions are
then based on the International Consensus Classification (9).
Serum markers and imaging are used to assess response to chemotherapy. Residual
masses may persist after completion of treatment. Patients with seminoma do not
generally require resection of a persistent mass, as the presence of residual viable
seminoma and the development of recurrence are rare (34, 35). On the other hand, in
patients with teratoma, over half of resections contain viable disease, and it is not
possible to identify preoperatively those with fibrosis or necrosis only (34, 36). The
presence of malignant germ cell elements (10%) other than teratoma differentiated,
(50% of cases), and incomplete resection are independent risk factors for progression
(36-38). The presence of undifferentiated teratoma has been identified as the single
most significant risk factor for progression in patients with complete resections (38).
Patients with teratoma differentiated in their primary orchidectomy are more likely to
have an incomplete response and are at higher risk of harbouring teratoma differentiated
in residual masses, and therefore viable persistent tumour (39). However the absence of
teratoma differentiated from the primary tumour does not preclude its presence in
metastases (40, 41). The presence of cytologically atypical epithelial or mesenchymal
elements in teratoma differentiated is not uncommon in post-chemotherapy specimens
and does not alter prognosis. However, if the somatic cells show invasive pattern this is
indicative of secondary transformation towards a somatic malignancy, which is
associated with a higher risk than teratoma differentiated alone (42).
5.13
Reporting of Biopsy Specimens
Testicular biopsies are most commonly performed in the context of infertility and
intratubular germ cell neoplasia (TIN) may be an incidental finding. If untreated, invasive
testicular tumour develops in 70% of cases within 7 years (43).
The rationale for performing contralateral biopsies in patients with germ cell tumours is to
consider offering the option of low-dose irradiation to prevent the development of an
invasive germ cell tumour and the need for a second orchidectomy and therefore
complete androgen ablation. However, the value of routine biopsies is controversial as
10
the overall prevalence is low (5%) and up to 25% of patients treated for TIN develop
androgen insufficiency requiring testosterone supplementation (44-46). Nevertheless,
patients with an atrophic contralateral testis and who present before the age of 30
appear to be at higher risk and may be offered biopsy (45). Generally three levels are
taken. It is useful to retain spare sections of immunocytochemistry in case of doubt about
the diagnosis of TIN. A Feulgen stain can be useful for the rapid identification of
spermatozoa as they are bright red in a blue background. Opinions are divided
concerning the value of Bouin's fixation (12, 47). It offers better cytological detail and
allows a better assessment of spermatogenesis but can adversely affect the results of
immunocytochemistry. Formalin fixation can induce artefact with ballooning of the
cytoplasm, mimicking neoplasia, but most cases can be resolved with the use of
markers.
5.14
Macroscopic Items
Biopsies are measured and completely embedded.
5.15
Microscopic Items
•
Approximate number of tubular cross-sections present.
•
Assessment of spermatogenesis.
•
Presence or absence of TIN.
5.16
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 tumours 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, non-squamous somatic
elements or TIN. Urologists and their patients must be made aware of the inherent
difficulties of the technique and these potential pitfalls.
TNM Staging – see Appendix C.
6.
RADIOLOGY GUIDELINES
6.1
Clinical Background
The patterns of spread of testicular tumours are predictable. NSGCT typically spreads
initially to the retroperitoneal lymph nodes, but pulmonary metastatic disease may be
seen at first presentation. Seminoma metastasises to lymph nodes in the
retroperitoneum, and eventually mediastinum, rarely involving lung and other organs.
6.2
Imaging
Following orchidectomy and an established diagnosis of a testicular germ cell tumour, all
patients should be staged with CT. For NSGCT, this should include chest, abdomen and
11
pelvis. Follow-up depends on disease stage at presentation, and some patients may be
suitable for surveillance programmes.
6.3
Recommendations for Cross-Sectional Imaging in Cancer Management
August 2006
All patients with seminoma should be staged with CT of abdomen and pelvis at
presentation. It is an option to include thoracic CT in the initial assessment, as the
discovery of retroperitoneal nodal enlargement would necessitate thoracic CT.
6.4
Staging objectives
•
•
•
•
To detect lymph node metastases in abdomen, thorax and supraclavicular
fossa.
To identify lung metastases.
To identify disseminated blood-borne metastatic disease, e.g., liver.
To identify brain metastases in selected patients.
Note that the primary tumour is not assessed by CT or MRI.
6.5
Staging Nodal and Metastatic disease
6.5.1
CT
CT is the preferred investigation, as it remains the most sensitive modality for identifying
small (less than 1 cm) pulmonary metastases. For NSGCT, because of the relatively
high incidence of chest deposits, CT scanning of whole body is preferred. At initial
staging of all germ cell tumours contrast-enhanced CT of the thorax, abdomen and
pelvis should be obtained although subsequently the pelvis may be omitted particularly
in patients who have no prior history of inguinal-scrotal surgery. However, in patients
who have had a scrotal incision, inguinal hernia repair, or developed testis cancer in an
ectopic / undescended testis, the pelvis should be imaged on follow-up examinations.
•
•
•
•
•
•
Oral administration of 1 litre of water or iodinated contrast medium.
100-150 ml of intravenous iodinated contrast medium injected at 3-4
ml/sec.
MDCT is commenced at 25-30 seconds post-injection to assess the
thorax and 70-80 seconds post-injection to assess the abdomen and
pelvis.
Alternative protocol for 16-slice MDCT: commence scanning at 50
seconds post-injection to include chest, abdomen and pelvis.
A maximum slice thickness of 5 mm is required using spiral technique.
Using MDCT, slice thickness will depend on scanner capability. In
general, sections are acquired at 1.25-2.5 mm and reformatted at 5 mm
for viewing.
Values of CTDIvol should normally be below the relevant national reference dose for the
region of scan and patient group.
6.5.2
MRI
12
MRI has similar sensitivity to CT for detection of nodes in the retroperitoneum but in
general is not used for this purpose. MRI is the technique of choice for detecting brain
metastases. If a patient presents with more than 20 pulmonary metastases or HCG level
greater than 100,000 or other IGCCCG poor prognostic features brain deposits are
sufficiently likely that MRI is indicated. The trophoblastic subtype of NSGCT is also
associated with a high incidence of brain deposits. The brain may act as a “sanctuary
site” for NSGCT deposits during treatment with chemotherapy.
7.
GUIDELINES ON FERTILITY SUPPORT SERVICES
All patients are referred for sperm banking if they are to undergo chemotherapy. Any
patients with suspected infertility or solitary testes will also be invited to carry out sperm
banking pre-orchidectomy.
13
8.
TREATMENT PROTOCOLS
8.1
Seminoma
Stage I
Approximately 75% of patients have stage 1 disease and survival rates are >99%
regardless of the management strategy chosen.
Surveillance
In surveillance following radical orchidectomy recurrences can occur late (up to 2 - 5
years) necessitating long term CT based follow up. The main advantage to surveillance
is that most patients do not require any further treatment. The disadvantages to
surveillance are the need for longer follow-up, the requirement for a greater number of
CT scans (and thus the increased amount of irradiation) and the psychological morbidity
of living with a significant chance of relapse (15%) which requires relatively tough
chemotherapy. (48, 49)
Adjuvant chemotherapy
A single cycle of carboplatin AUC 7 reduces the risk of relapse to <5% if an EDTA
creatinine clearance is used to direct the dosing of carboplatin and also reduces the risk
of a contralateral GCT at least in the medium term with 6.5 years of study follow up
reported (50, 51)
Adjuvant radiotherapy
This is as effective as adjuvant carboplatin but has more side effects, a worse quality of
life after treatment and has a small, but significant chance of inducing a second
malignancy in the long term and therefore is rarely used (50, 52).
All options for the management of stage I seminoma of the testis result in a very high
cure rate as salvage chemotherapy is effective for relapse. Patients are offered the
choice of surveillance or adjuvant chemotherapy and the advantages and disadvantages
of both discussed.
14
Stage II
Although abdominal radiotherapy remains an option (especially for stage IIA disease)
combination cisplatin-based combination chemotherapy is commonly used (BEP for 3
cycles or EP for 4 cycles if contraindications to bleomycin).
Stage III - IV
Standard 3-day BEP chemotherapy for 3 cycles (good prognosis) or EP for 4 cycles if
contraindications to bleomycin. Intermediate prognosis patients receive 4 cycles of BEP
on a 5-day schedule (see Table 1).
Table 1: IGCCCG International prognostic classification for Seminoma (9)
Good prognosis group
Proportion of patients 90%
5-year survival 86%
Intermediate prognosis group
Proportion of patients 10%
Seminoma
Any primary site
No non-pulmonary visceral metastases
Normal AFP, any bHCG or LDH
Seminoma
Testis or retro-peritoneal primary site
Non-pulmonary visceral metastases
Normal AFP, any bHCG or LDH
5-year survival 72%
8.2
NSGCT
Stage I
Serum tumour markers should be monitored weekly until normal. Markers which fail to
normalise are treated as per metastatic NSCGT.
The majority of relapses occur within the first 12 months and patients are divided into low
(15-20% risk) and high risk groups (40-50% risk) for recurrence according to whether or
not lympho-vascular invasion is present. It is especially important that all cases have
detailed histological review at the MDT. For the high risk group, 2 cycles of adjuvant
BEP chemotherapy are recommended (unless patients agree to enter the III study which
is examining the role of a single cycle of adjuvant chemotherapy) (53)
Patients in the low risk group are offered surveillance after radical orchidectomy. The
follow up is intense and it is important that they have a high level of compliance (see
10.3.1) (32). Some patients with low risk disease however still opt for adjuvant
chemotherapy, mainly for the knowledge that after such treatment risk of relapse is
remote.
15
Stages IM - IV
Combination cisplatin based chemotherapy for 3-4 cycles, depending on the prognostic
group (table 2).
Treatment algorithm - see Appendix D.
Table 2: IGCCCG International prognostic classification for NSGCT (9)
Good prognosis group
Proportion of patients 56%
5-year survival 90%
Intermediate prognosis group
Proportion of patients 28%
5-year survival 80%
Poor prognosis group
Proportion of patients 16%
5-year survival 50%
NSGCT – ALL of:
Testis or retroperitoneal primary site
No nonpulmonary visceral metastases
AFP < 1000 ng/ml, beta HCG < 5000IU/L, LDH < 1.5 x ULN
NSGCT – ALL of:
Testis or retroperitoneal primary site
No non-pulmonary visceral metastases
Any of: AFP ≥ 1000 and ≤ 10,000 ng/ml
bHCG ≥ 5000 and ≤ 50,000 IU/L
LDH ≥ 1.5 ≤ 10 x ULN
NSGCT – ANY of:
Mediastinal primary site
Non-pulmonary visceral metastases
AFP > 10,000 ng/ml; bHCG > 50,000 IU/L; or LDH >10 x
ULN.
For management purposes the extent of tumour spread is divided into four stages based
on the Royal Marsden Hospital staging system (table 3).
Table 3
STAGE
I
IM
II
III
IV
ANATOMICAL EXTENT
Tumour confined to the testis. No evidence
of distant spread
As above but persistently elevated markers
Infradiaphragmatic lymph node
involvement:
IIA - diameter < 2 cm
IIB - diameter 2 – 5 cm
IIC - diameter > 5 cm
Supra and Infra-diaphragmatic lymph node
involvement
A,B,C categories: as above
Extralymphatic (nonpulmonary) visceral
metastases
16
9.
PRE-CHEMOTHERAPY WORK UP
For all patients who are to have chemotherapy the specialist nurse will be available to
explain the process and to provide them with written information. This will be reiterated
when the patient attends Clatterbridge Centre for Oncology. The timing of chemotherapy
cycles is important, as are arrangements and expectations for time off work, support
from social services and arrangement for transport to and from the hospital.
Cisplatin is nephrotoxic and adequate baseline renal function is required for
administration, with the dose based on the patient’s weight and height. The drug is given
intravenously with a crystalloid infusion to maintain good renal perfusion. It can induce
significant nausea and vomiting. In addition cisplatin is neuro-toxic and can result both
in peripheral neuropathy affecting the fingers and toes and ototoxicity causing loss of
high frequency hearing. Although often reversible, the process can take up to 2 years to
recover. Bleomycin has the rare but fatal complication of progressive pulmonary fibrosis
causing irreversible damage to the lung resulting in progressive and ultimately fatal
hypoxia. Etoposide can induce marrow suppression resulting in a fall in white cells and
platelets. Cases of secondary leukaemia have been described. Any sign of infection or
abnormal bruising requires prompt attendance at the hospital. Hair loss (alopecia) is
universal as is tiredness. Other common side effects include taste change, a sore
mouth, acne, skin pigmentation and runny eyes.
Of particular importance is the effect of the chemotherapeutic agents on the germinal
epithelium of the remaining testis. Spermatogenesis is eradicated by the chemotherapy
but frequently returns to normal after about 12 months. For this reason all patients are
offered sperm banking before starting chemotherapy. If for some reason
spermatogenesis did not return, in vitro fertilisation would be an option for the couple.
There is no evidence to suggest that a pregnancy may be abnormal if it occurs while
spermatogenesis is undergoing recovery, and so contraception is not required (54).
Long term late complications remain an area of investigation but secondary
malignancies and cardiovascular disease have both been associated with GCT
chemotherapy (55, 56). Patients should be counselled regarding long term toxicity at the
time of consent and every effort made to provide smoking cessation advice and support
where required.
For those teratoma patients with abdominal or thoracic metastases, chemotherapy may
eradicate them completely. However where residual masses remain it is usually
appropriate to excise them surgically, and informing the patient at an early stage that
treatment is a combination of chemotherapy and surgery allows the patient to
understand the treatment plan.
17
10.
FOLLOW-UP
The follow up schedule takes into account the site and likely timing of relapse.
10.1 Stage 1 seminoma
Surveillance
In over 90% of patients with stage 1 seminoma the first site of relapse is the infradiaphragmatic (para-aortic) nodes (57).
Adjuvant carboplatin
Following chemotherapy relapse is rare but most likely to occur in the infradiaphragmatic
nodes (usually para-aortic nodes) (57)
Adjuvant radiotherapy
Following para-aortic radiotherapy, relapse is most likely in the pelvic lymph nodes. With
‘dog-leg’ radiotherapy, the first detected site of relapse is more likely in the chest, or
palpable neck or inguinal lymph nodes) (57)
Table 4: Suggested surveillance for stage 1 seminoma post orchidectomy
Intervention
Examination &
Markers*
CXR and CT
abdomen†
Year 1
3 monthly
Year 2
3 monthly
Year 3
6 monthly
Year 4
6 monthly
6 monthly
6 monthly
End of
year 3
End of
year 4
Year 5
6 monthly
Year 6+
Discharge at
end of year 5
Table 5: Suggested follow up for stage 1 seminoma following adjuvant carboplatin
Intervention
Examination &
Markers*
CXR and CT
abdomen†
Year 1
3 monthly
Year 2
3 monthly
End of
year 1
End of
year 2
Year 3
6 monthly
Year 4
6 monthly
Year 5
6 monthly
Year 6+
Discharge at
end of year 5
Table 6: Suggested follow up for stage 1 seminoma following adjuvant radiotherapy
Intervention
Examination &
Markers*
CXR +CT
pelvis
(paraaortic
radiotherapy)
* AFP and bHCG
Year 1
3 monthly
Year 2
3 monthly
Year 3
6 monthly
End of
year 1
End of
year 2
End of
year 3
Year 4
6 monthly
Year 5
6 monthly
Year 6+
Discharge at
end of year 5
† CT to include pelvis if prior inguino-scrotal surgery
18
10.2
Metastatic seminoma
Table 9: Suggested follow up for metastatic seminoma (radiotherapy or chemotherapy)
Intervention
Examination
& Markers*
CXR + CT
abdomen†
10.3
Year 1
Year 2
Year 3
Year 4
Year 5
Year 6+
Consider
3 monthly 3 monthly 6 monthly 6 monthly 6 monthly discharge
at end of
year 5
If post treatment CT abdomen/pelvis is normal, no further routine CT
scans. If post treatment scan abnormal, repeat at 4-6month intervals, but
stop as soon as normal / stable
Stage 1 NSCGT
Surveillance
Following orchidectomy for NSGCT, patients may be assigned Stage 1, if there is no
distant spread on CT and can enter a surveillance programme which involves serum
tumour marker estimations and regular CT follow-up. Of those patients with Stage I
tumours who will relapse (15-20%), 80% will do so within 1 year, and >95% within 2
years.
Table 7: Suggested follow up for low risk Stage 1 NSCGT post orchidectomy
Intervention
Year 1
Year 2
Year 3
Year 4
Year 5
Examination &
Markers*
monthly
2 monthly
3 monthly
4 monthly
6 monthly
CXR + CT
abdomen†
3 and 12
months
Year 6+
Consider
discharge
at end of
year 5
No further routine scans
For high risk stage 1 NSCGT who do not elect to receive adjuvant chemotherapy and
enter surveillance, it is suggested that CT thorax and abdomen is performed at 3, 6, 12
and 24 months
19
Adjuvant chemotherapy
Table 8: Suggested follow up following chemotherapy for high risk stage 1 NSCGT post
orchidectomy
Intervention
Year 1
Year 2
Year 3
Year 4
Year 5
Examination
& Markers*
2 monthly
3 monthly
6 monthly
6 monthly
6 monthly
CXR + CT
abdomen†
10.4
Year 6+
Consider
discharge
at end of
year 5
No routine scans required
Metastatic NSCGT
Table10: Suggested follow up for patients following treatment for metastatic NSGCT
Intervention
Examination
& Markers*
CXR + CT
abdomen†
Year 1
Year 2
Year 3
Year 4
Year 5
Year 6+
Consider
2 monthly 3 monthly 6 monthly 6 monthly 6 monthly discharge
at end of
year 5**
If post treatment CT thorax/abdomen is normal, no further routine CT
scans. If post treatment scan abnormal, repeat at 4-6 month intervals, but
stop as soon as normal / stable
** Long term follow up required annually if TD in resection specimen.
Further notes



Brain metastases are haemorrhagic and are frequently clearly identified on precontrast scans using CT or MRI.
Nodal metastases in NSGCT may become cystic on treatment.
PET CT is indicated for residual masses in seminoma >3cm and >1cm in
NSCGT, also detection of relapse in NSCGT and seminoma where standard CT
scans are normal / indeterminate
20
10.5 Management of Post-Chemotherapy Residual Masses
Following successful treatment with chemotherapy a further CT scan is required about 4
weeks later to assess the metastatic disease. The post-treatment CT scan is reviewed in
the MDT. In patients with teratoma where residual masses remain (usually >1 cm)
surgical excision is required.
For patients with seminoma, residual masses have been shown to be nearly always
necrotic and due to the intense fibrosis that occurs adjacent to them surgical excision is
not regarded as necessary or wise. In the case of residual tumour >3cm a PET scan at
least 6 weeks after chemotherapy may be indicated. If the mass is PET positive then this
is strong evidence for active tumour and resection should be considered (58). In the
absence of a PET scan lesions >3cm should be followed only until regression or
progression.
Surgery for retro-peritoneal para-aortic masses requires the patient to be prepared with
considerable care. The surgery is usually performed through a long midline abdominal
incision or via a thoraco-abdominal incision. Residual masses usually lie adjacent to the
aorta and often close to the renal artery. To perform complete excision of these masses
it is sometimes necessary to include a nephrectomy to remove the masses en bloc. For
this reason, the patient requires a pre-operative intravenous urogram to confirm both
kidneys function normally and to help define the location of the para-aortic masses.
During the dissection within the standard template along the aorta the sympathetic
nerves may be divided which can lead to retrograde ejaculation. The patient needs to be
informed of this risk.
Although pulmonary function tests, including the transfer factor, can be normal in
patients following bleomycin chemotherapy, there is evidence that these patients are at
a higher risk of developing reduced gas transfer intra-operatively either due to oxygen
sensitivity or relative pulmonary oedema if over-transfused with crystalloid (59).
All tissue following such surgery is examined histologically. About 40% of cases show
necrotic tissue resulting from tumour death following the chemotherapy. About 40% 50% show mature or differentiated teratoma. This tissue has responded to the
chemotherapy by differentiating, but has the potential to de-differentiate at a later time.
Such tissue may develop back into teratoma or squamous or sarcomatoid differentiation
can be seen. It is for this reason that complete excision of residual masses is important.
In 10%, there is residual malignant teratoma present within the excised mass (60).
Depending on the extent of the disease and the patient’s tumour marker status further
chemotherapy or surveillance may be recommended (61).
Follow up after resection of residual masses
A post-operative follow up appointment at 4 to 6 weeks is made for assessment of
wound healing and any complications.
The histology of the resected masses is reviewed in the testis MDT.
The intensity of post treatment follow up is determined by the prognostic group the
patient was in at presentation and how well they have responded to treatment.
21
Teratoma patients who have required post chemotherapy node dissection will require
long term follow up and CT scanning if the histology showed differentiated teratoma or
active tumour was found.
For patients who develop post treatment relapse the outcome is less good. Second line
chemotherapy ha a 40% complete remission rate, probably because of the development
of multiple drug resistant tumour differentiation. Response to chemotherapy however is
not always durable and the surgical resection of any residual masses remains an integral
part of the patient’s management.
Management of Post-treatment Relapse Patients
(i) Tumour marker relapse.
Rising tumour marker levels will usually precipitate further imaging to identify metastatic
disease or a new primary tumour; this usually requires CT of chest, abdomen and pelvis
together with ultrasound of the remaining testicle. If no new disease is seen, an MRI of
the brain is also indicated as this may be a site of occult metastatic disease. 18FDG
PET-CT should also be considered.
(ii) recurrence of distant metastases.
Salvage chemotherapy is available for patients with relapsed disease with bone marrow
transplant support available if required (Professor Richard Clarke, Royal Liverpool
Hospital).
11.
MANAGEMENT
TUMOUR
OF
METACHRONOUS
CONTRALATERAL
TESTIS
Should this occur, the patient will be managed in exactly the same way as a patient with
a new diagnosis of a testicular tumour, although matters of fertility and subsequently
hormone replacement therapy will be discussed if orchidectomy and therefore complete
castration is anticipated. Professor Vora, Consultant Endocrinologist at the Royal
Liverpool Hospital kindly supplies a clinical service for hormone replacement therapy.
12.
SPECIALIST PALLIATIVE CARE
There are some patients who are particularly likely to require specialist palliative care.
Referral is made as early in the patient’s disease course as is possible. These include:
• Patients with pre-existing psychological problems.
• Patients with young children.
• Patients with complex or multiple symptom control problems.
• Patients with disfiguring illness.
• Patients with personality change
Issues of hydration and nutrition are often problematic for patients, carers and health
care professionals. Where no improvement can be achieved by further treatment of the
tumour, time must be given to gentle and through explanation of the situation, and what
22
can realistically be achieved. Specialist palliative care input may be required to assist
with these discussions.
It is inappropriate to try to stimulate appetite (e.g. with steroids) when ingestion is painful,
limited or difficult. Patients are usually able to take sufficient, often in the form of
nutritional liquid supplements, to satisfy thirst and appetite.
Meticulous attention must be paid to:
 Mouthcare – seek specialist nurse advice.
 Pain control – use of regular non-oral medication.
 Anti-emesis – delivered via subcutaneous infusion where necessary.
 Relief of constipation – regular non-bulk forming laxative plus rectal measures as
necessary.
 Haematuria
 Continence problems
 Catheter problems
Intravenous or subcutaneous hydration and PEG /jejunostomy for enteral feeding are
rarely indicated or required and should only be used with specialist advice.
How to Obtain Urgent Symptom Control Advice
District General Hospital Input
-
Primary Care
Contact Specialist Community Team
-
Contact Specialist Hospital Team
Each team will have individual arrangements or out of hours access to advice and
review.
The Liverpool Care Pathway for the Dying Patient (LCP) has been developed in the U.K
to transfer the hospice model of care into other care settings. It is a multi-professional
document that provides an evidence- based framework for end of life care.
The LCP provides guidance on the different aspects of care required, including comfort
measures, anticipatory prescribing of medicines and discontinuation of inappropriate
interventions.
Additional, psychological and spiritual care and family support are
included.
13.
CLINICAL TRIALS
All patients that are suitable for any current National Clinical Trials are considered at the
time of the Specialist MDT and would be seen by the Research Practitioner Nurses, who
co-ordinate clinical trials.
23
14.
PATIENT INFORMATION
All patients will be offered clear and comprehensive information in a format which is
suitable to their needs and their stage of treatment in the cancer journey.
This should include











Nature of the disease
Diagnostic procedures being undertaken
Treatment options available
Likely outcomes of treatment in terms of benefits, risks and side effects
Management of side effects of treatment, and who would be most appropriate to
contact for advice
Details of future appointments/contacts
Contact details of clinical nurse specialist/key worker for urological cancers
Contact details of clinical nurse specialist for other individual issues (stoma
care/continence advice/sexual issues/body image issues) as appropriate
Cancer information services such as Cancer BACKUP
Where appropriate patients should receive a copy of any medical/clinical
communications.
Details of MDT
Hard copies of the information, available within the Merseyside and Cheshire Cancer
Network for patients with urological cancer and their carers, can be obtained from the
clinical nurse. This information will meet agreed MCCN / National Patient Information
Guidelines, as per mapping
Access will be made available for all patients/carers to a named nurse whose specialist
knowledge is in urological cancers.
Patients in the 16 – 24 year age group will be notified to the Teenage and Young Adult
MDT to ensure that appropriate psycho-social support is available from the dedicated
TYA specialists within the team eg CLIC Sargent social worker.
24
Appendix A - Pathway
Patient presents with Testis Tumour
Acutely ill – Peter Clark/Judith
Carser
IMMEDIATELY
Otherwise – Pre-op markers
Radical Orchidectomy
Advice about body image & Testis
Prosthesis
Within 24 hours
Refer directly to Peter Clark/Judith
Carser
postop markers
Key:
Histology and radiology reviewed
for SMDT
Local Urology Team
Specialist Testis Team
Patient staged: CT scan at
RLBUHT if not already done
Within 2 weeks
Long term
follow-up
Surveillance & repeat
CT scans
Patient seen – results &
treatment plan agreed
Advice about Sperm banking
Relapse
Follow-up
Clear CT
Chemotherapy
Repeat CT
Decision about RPLND Surgery or
resection of other residual masses
Follow-up
Within 2 months of decision re surgery
Relapse
Histology and Followup
Surgery
Post Surgery CT
Consider salvage options:
Surgery Chemo
High dose
chemotherapy
transplant
25
APPENDIX B
DEPARTMENT OF PATHOLOGY
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITAL TRUST
STANDARD OPERATING
PROCEDURE
HT78000: 1(4)
AUTHORISED BY: PAS
REVISION: 8
CHECKED BY: VIA
REVISION DATE: 23/09/09
PREPARED BY: VIA
DATE: 23/09/08
AREA: HISTOLOGY: HANDLING AND CUT-UP OF SURGICAL SPECIMENS
TESTIS
PURPOSE
Adequate examination, sampling, description and diagnosis of specimen.
PERSONNEL
Medical and Technical Staff.
1.
Handling at cut-up:
a)
Weigh: y
b)
Ink margins: n
Tumour:
Open the tunica vaginalis, weigh and measure the testis.
Cut the testis sagitally, while it is in a fresh state and fix in formalin.
Cut serial slices, about 3mm thick, of each testicular half, perpendicular to the
original section, stopping just at the level of the tunica albugenea and examine
each surface.
Cut the epididymis longitudinally throughout its length.
2.
3.
Special features for description:
Size of testis in 3 dimensions
Length of spermatic cord
Tumour – size in 3 dimensions, colour, consistency, homogeneity or lack of it,
presence of cysts, necrosis, haemorrhage, bone or cartilage-, tumour extension
to tunica albugenea, epididymis, cord and other structures.
Features of non-neoplastic testis-, atrophy, fibrosis or nodules.
Blocks - from where and how many:
Tumour: at least three blocks or one section for each centimetre of tumour,
whichever is greater; at least one of which should include some uninvolved
testis.
Uninvolved testis: two blocks.
Epididymis.
Spermatic cord and surrounding soft tissue at point 1cm from testicle -, one
cross section block.
26
Spermatic cord and surrounding soft tissue at line of resection; one cross
Copyright 9 Department of Pathology, RLBUH NHS Trust
HT78000: 2(4)
section block.
4.
Routine special stains: None.
Ziehl-Neelsen staining may be required if tuberculosis is suspected, but note
that this is often spuriously positive in the testis anyway because the sperm
heads contain a ZN-positive protein.
5.
Processing - special instructions: None.
6.
Report: Specific features to include:
Neoplasms
Reporting should be according to the British Classification and, in the case of
teratoma, should mention the presence of venous or lymphatic invasion,
undifferentiated elements, amount and type of differentiated tissue, and the
presence or absence of trophoblastic and yolk sac differentiation. The report
should include all the data required by the "Minimum dataset for testicular
tumour histopathology reports" issued by the Royal College of Pathologists,
April 2000 (see below).
BRITISH CLASSIFICATION
Classification of tumours of testis, epididymis and related structures.
1.
TUMOURS OF THE TESTIS
Seminoma (S):
Teratoma:
Classical
Spermatocytic
Anaplastic
Teratoma Differentiated (TD)
Malignant Teratoma Intermediate (MTI) with
differentiated or organoid components, but also
containing undifferentiated elements.
Malignant Teratoma Undifferentiated (MTU) with no
mature tissues or organoid structures.
Malignant Teratoma Trophoblastic (MTT)-existing
cyto and syncytotrophoblastic differentiation arranged
in a papillary growth pattern.
Yolk-sac Tumours (YST)
Combined Tumour:
Seminoma and teratoma in the same testis (CT)
Sertoli-cell/ Mesenchyme Tumours (SMT)
Interstitial-cell Tumours (ICT)
Malignant Lymphomas
Miscellaneous Tumours
Metastases
Tumours of Uncertain Diagnosis
27
Copyright Q Department of Pathology, RLBUH NHS Trust
HT78000: 3(4)
2.
TUMOURS OF EPIDIDYMIS AND CORD
Adenomatoid Tumour
Tumours of Connective Tissue and Muscle
Subdivided into:
Benign:
Fibroma, leiomyoma, lipoma, etc.
Malignant:
Embryonic sarcoma, fibrosarcoma, leiomyosarcoma, etc.
Miscellaneous Tumours
Metastases
Tumours of Uncertain Diagnosis
TESTICULAR BIOPSIES - JOHNSEN COUNTS
Tubular cross-sections in one histological section of each testicular biopsy a re
evaluated systematically and each cross-section is given a score from 1 -10 according
to the following criteria:
Score
10
9
8
7
6
5
4
3
2
1
Complete spermatogenesis with many spermatozoa; germinal epithelium
organised in a regular thickness leaving an open lumen.
Many spermatozoa present but germinal epithelium shows marked sloughing or
obliteration of the lumen.
Only few spermatozoa (<5-10) present in section.
No spermatozoa, but many spermatids present.
No spermatozoa and only a few spermatids (>5-10> present.
No spermatozoa, no spermatids but several or many spermatocytes present.
Only few spermatocytes (<5) ad no spermatids or spermatozoa present.
Spermatogonia are the only germ cells present.
No germ cells but Sertoli cells are present.
No cells in tubular section.
A mean score for each testis is calculated as in the following example:
(1)
Score
10
9
8
7
6
5
4
3
2
1
Total
(2)
No. of tubules with score
63
14
8
14
0
1
1
0
0
0
101 (3)
(1) x (2)
630
126
64
98
0
5
4
0
0
0
927 (4)
Copyright Q Department of Pathology, RLBUH NHS Trust
28
HT78000: 4(4)
Mean score = (4) / (3) = 927 / 101 = 9.2
Notes:
1.
2.
3.
4.
Bouin's fluid should be used for fixation of the biopsy.
This testicular biopsy score system devised by Johnsen provided an accurate
method of registering the degree of spermatogenesis, and gives a
mathematical index of the functional state of the testicular tissue.
The mean score in normal testes is 9.38 0.48 (Mean 2 S.D.).
Analysis of results suggests that pregnancy is unlikely with a score count of less
than 6.0 which represents the point at which spermatids appear in the tubules
in the biopsy material.
Risk Assessment
See SOP No. HT00100 for risk assessment guidelines.
29
Copyright Q Department of Pathology, RLBUH NHS Trust
APPENDIX C - TNM PATHOLOGICAL STAGING (7th EDITION) (62)
The classification applies only to germ cell tumours of the testis. The assessment of the
serum tumour markers alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG)
and lactate dehydrogenase (LDH) contributes to the staging.
30
Appendix D
Treatment algorithm
Pre-operation:
Tumour marker estimation
Operation:
Radical orchidectomy
Post-operation:
Tumour marker estimation: Staging CT scan
Histological assessment:
Seminoma, NSGCT, other
Seminoma
Stage I
adjuvant chemotherapy or surveillance,
consider (para-aortic radiotherapy only if contraindication to the above)
Stage II
stage IIA abdominal radiotherapy is an option
stage IIa-c – chemotherapy BEP x 3
Stage III and IV
Good prognosis: BEP x 3 (3 day regimen)
Intermediate prognosis: BEP x4 (5 day
regimen)
NSGCT
Low risk
surveillance
Stage I
High risk
Stage II, III, IV
2 cycles BEP
Good prognostic group: BEP x 3 (3 day regimen)
Intermediate /poor prognostic group: BEP x 4 (5
day regimen).
Secondary prophylaxis with pegfilgrastim is indicated following any episode
which may compromise dose intensity (eg neutropenic sepsis, uncomplicated
neutropenia resulting in treatment delays)
31
Appendix E
Chemotherapy protocols
Adjuvant
Stage 1 pure seminoma
Carboplatin AUC 7 for one cycle (based on EDTA creatinine clearance)
Stage 1 NSCGT
High risk tumours LVI +
BEP3 Bleomycin
Etoposide
Cisplatin
30000iu iv days 1,8,15
165mg/m2 iv days 1-3
50mg/ m2 iv days 1,2
21 day intervals for 2 cycle
Metastatic
Good prognosis –all GCT
BEP3 Bleomycin
Etoposide
Cisplatin
30000iu iv days 1,8,15
165mg/m2 iv days 1-3
50mg/ m2 iv days 1,2
21 day intervals for 3 cycles
AFP, bHCG day 1 each cycle
CXR day 1 each cycle review by radiologist
CT CAP one month post treatment
32
Intermediate – poor prognosis all GCT
BEP5 Bleomycin
Etoposide
Cisplatin
30000iu iv days 1,8,15
100mg/m2 iv days 1-3
20mg/m2 iv days 1,2
21 day intervals for 3 cycles, then EP5 for cycle 4 (ie omit bleomycin)
AFP, bHCG day 1 each cycle
CXR day 1 each cycle review by radiologist
CT CAP one month post treatment
Initial organ failure / poor performance status
Etoposide
Cisplatin
100mg/m2 iv days 1-3
20mg/m2 iv days 1-3
Repeat daily x 2-3 depending on clinical scenario. Aim to revert to full dose BEP
one week later
Relapsed GCT
TIP
Paclitaxel 175mg/m2 day 1 iv
Ifosfamide 1000 mg/m2 days 1-5 iv
Cisplatin 20mg/m2 days 1-5 iv
Repeat at 21 days x 4 cycles
33
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