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
CONTENTS / Page1. / Introduction / 4
2. / Details of the Testis MDT / 5
3. / GP referral guidelines / 5
4. / Initial management of a suspected testicular tumour and local MDT referral guidelines / 5-6
5. / Pathology guidelines / 6-11
5.1 / Clinical Information Required on the Specimen Request Form / 6-7
5.2 / Preparation of Specimens before Dissection / 7
5.3 / Specimen Handling and Block Selection / 7
5.4 / Gross Examination of Orchidectomy Specimens / 7-8
5.5 / Primary Lymphadenectomy Specimens / 8
5.6 / Excision of Residual Masses after Chemotherapy / 8
5.7 / Block Selection / 8
5.8 / Orchidectomy Specimens for Clinically Localised Disease / 8
5.9 / Retroperitoneal Lymph Node Dissections and Post-chemotherapy Residual Masses / 8-9
5.10 / Classification of Testicular Tumours / 9
5.11 / Pathological Prognostic Factors in Stage 1 Disease / 9-10
5.12 / Metastatic Disease and Post-chemotherapy Residual Masses / 10
5.13 / Reporting of Biopsy Specimens / 10-11
5.14 / Macroscopic Items / 11
5.15 / Microscopic Items / 11
5.16 / Reporting of Frozen Sections / 11
6. / Radiology guidelines / 11-12
6.1 / Clinical background / 11
6.2 / Who Should be Managed? / 11
6.3 / Recommendations for Cross-Sectional Imaging in Cancer Management August 2006 / 11
6.4 / Staging Objectives / 12
6.5 / Staging Nodal and Metastatic Disease / 12
7. / Guidelines on Fertility Support Services / 13
8. / Treatment protocols / 14-16
8.1 / Seminoma / 14-15
8.2 / NSGCT / 15-16
9. / Pre-chemotherapy preparation of the patient / 17
10. / Follow up protocols / 18-22
10.1 / Stage 1 seminoma / 18-19
10.2 / Metastatic seminoma / 19
10.3 / Stage 1 NSGCT / 19-20
10.4 / Metastatic NSCGT / 20
10.5 / Management of residual masses post chemotherapy / 21-22
11. / Management of Metachronous Contralateral Testis Tumour / 22
12. / Specialist Palliative Care / 22
13. / Clinical Trials / 23
14. / Patient Information / 24
APPENDICES
Appendix A - Pathway / 25
Appendix B - Histology: Handling and Cut-up of Surgical Specimens / 26-29
Appendix C - TNM Pathological Staging
Appendix D - Treatment Algorithm
Appendix E – Chemotherapy protocols / 30
31
32-33
REFERENCES / 34-38
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 non-seminomatous 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).
2. DETAILS OF THE TESTIS MDT
Core members:
Peter Clark Consultant Medical Oncologist
Judith Carser Consultant Medical Oncologist
Doug Errington Consultant Clinical Oncologist
Mark Fordham Consultant Urological Surgeon
Vijay Aachi Consultant Histopathologist
Jane Belfield Consultant Radiologist
Iwan Lewis-Jones Consultant Andrologist
Nicola Wilson Clinical Nurse Specialist
Carmela Parisi / Claire Richards 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 Consultant Clinical Oncologist
Iwan Lewis-Jones Consultant Andrologist
Richard Page Consultant Thoracic Surgeon
Professor J Vora 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 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
Advice about body image & Testis
Prosthesis Within 24 hours
Key:
5. 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 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 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.