Management Of Stage 1 Testicular Cancer

Primary testicular tumours and management of Clinical Stage 1 Testicular Cancer

Elsie Ellimah Mensah1, David Nicol2, Erik Mayer1, 2

1 Imperial College London

2 Royal Marsden Hospitals

Introduction

Testicular cancer comprises 1% of cancers in men but is the commonest malignancy in young men aged 15-40 in Western populations.[1] The incidence has risen over the last 40 years globally. Mortality rates in Westernised countries is reducing reflecting improved therapeutic options and multidisciplinary specialist centre management.[2] With excellent cure rates there is an increasing focus on minimising treatment related side effects and morbidity.

Classification of testicular tumours

Testicular cancers are classified as germ cell tumours (GCTs) or sex cord-stromal tumours. Approximately 95% are GCTs [3] which are further classified as seminomatous germ cell tumours (SGCT) or non-seminomatous germ cell tumours (NSGCT) with the latter usually containing a mixture of histological sub-types [4].

Sex cord-stromal tumours comprise <5% of testicular tumours. The most relevant subtypes clinically are leydig cell tumours, which represent 70% of cases, and sertoli cell tumours.[5]

Demographics

The peak incidence for SGCT is 30-40 years and 20-30 years for NSGCT. [6] Leydig cell tumours commonly present between the third and sixth decades of life with an earlier peak in children aged 3-9 years. Sertoli cell tumours are rare and occur most frequently in men in their 40’s. [7]

Wide geographical variation in incidence rates is reported with lowest in Egypt and highest in Northern Europe.[6] These variations are likely to be influenced by both genetic susceptibility and environmental risk factors. Even within Northern Europe incidence varies, for example Denmark has twice the incidence of Finland.[8] Increasing incidence has been documented in specific Eastern European countries (e.g. Slovenia and Slovakia), suggesting environmental risk factor changes.[8]

Risk Factors and Aetiology The aetiology of GCTs is not fully understood. Intra-testicular germ cell neoplasia (ITGCN), also termed carcinoma in situ (CIS) is the accepted precursor. It is hypothesised that early disturbances in the differentiation of immature foetal germ cells initiates a cascade of changes leading to ITGCN which subsequently progresses to tumour formation generally in the post-pubertal period.[9]

Cryptorchidism, hypospadias and low sperm counts are well documented risk factors or associations with GCTs. Collectively grouped under the term testicular dysgenesis syndromes, they may reflect an unfavourable environment during testicular development in the prenatal stage (figure 1).

Figure 1: The testicular dysgenesis pathway. Reproduced with kind permission from [10].

Cryptorchidism is associated with a 4-8 times greater risk of developing testicular cancer. An alternative to the testicular dysgenesis pathway is that the maldescended testicle is exposed to an abnormal environment which subsequently leads to the formation of CIS and testicular cancer. Some studies have reported increased testicular tumour risk in patients who have had delayed orchidopexy compared with those who had it at a younger age. These findings have however not been shown in other studies and thus both theories remain valid albeit unproven. [6]

First degree relatives of patients with GCTs have a 4-8 fold increase in the risk - supporting a genetic contribution to a shared genetic and environmental risk model. Familial factors that have been postulated include an activation mutation in the KIT gene which has been detected in some sporadic and familial tumours, particularly bilateral tumours.[10,11]

A previous testicular tumour is a further risk factor for GCTs with a cumulative rate of approximately 5% reported.[6,12]. This closely reflects the incidence of CIS when biopsy of the contralateral testis is performed at time of initial presentation.

Testicular microlithiasis is frequently present in patients with GCTs although also common in the general population. In the absence of other risk factors, such as personal/family history of GCTs or cryptorchidism, microlithiasis is not an independent risk factor. [13] Increased oestrogen exposure during prenatal development has been postulated as an underlying factor in the genesis of GCTs and a possible explanation for the changing variation in incidence.[14]

Potential causes include plastics common in western environments and increased output of urinary oestrogens secondary to oral contraceptive pill use in women. It has been suggested that Bisphenol A (BPA), a known oestrogenic compound used in plastic manufacture and present in the resin lining of canned food and some dental sealants, may via hormonal effects, disrupt endocrine pathways during foetal development.[15] The finding of free BPA in human cord blood supports this hypothesis by confirming maternal absorption and placental transfer.[16] Current research is exploring pathways by which increased oestrogen exposure may have a carcinogenic effect. Transmembrane G protein receptor (GPER) is a promotor of oestrogen activity in germ cells[9] with potential roles in spermatogenesis and testicular development. In vitro BPA accelerates seminoma cell proliferation. This effect is obliterated by the addition of a specific GPER antagonist suggesting that BPA may have an effect on germ cell proliferation via GPER.[15]

As with all cancers GCTs are likely to have both initiators and promoters. Foetal events are likely to underpin the former. The fact that the vast majority of GCT present after puberty suggest that hormonal changes associated with this event may promote progression from CIS. Xenograft models of human GCTs have demonstrated that manipulation of the gonadotropin axis including FSH and LH significantly influences tumour growth supporting this hypothesis.[17]

Clinical Assessment

Testicular cancer usually manifests as a painless testicular lump although patients may uncommonly present with testicular pain, minor trauma or even epididymo-orchitis. The initial history should include identification of risk factors encompassing cryptorchidism as well as personal or family history of testicular tumours. Clinical examination must include the scrotum and a general assessment for signs of metastatic disease. These may include lymphadenopathy or a palpable abdominal mass. Respiratory tract signs may indicate pulmonary metastasis which necessitates urgent intervention.

Serum tumour markers (alpha-fetoprotein (AFP), lactate dehydrogenase (LDH) and human chorionic gonadotrophin (b-HCG)) should be routinely measured. Whilst negative results do not exclude GCT these are useful adjuncts for diagnosis and when raised pre-operatively, are critical to assessing response to treatment. Tumour markers can also be normal at presentation but rise with subsequent systemic relapse or the development of contralateral tumour.

AFP is produced by yolk sac cells and has a serum half-life of 3-5 days. It is produced in early development of the liver and not specific to testicular tumours with elevations in hepatocellular carcinoma, hepatic dysfunction and substance abuse misuse. Elevated levels with GCTs indicating a non-seminomatous component. It is raised in up to 70% of NSGCT.

B-HCG is a glycoprotein expressed by syncytiotrophoblasts and is raised in germ cell tumours particularly choriocarcinoma. The normal value is <5ng/ml (there may be local laboratory variability) with a half-life of 24-36 hours. Both SGCT and NSGCT can produce b-HCG with very high levels (>300ng/ml) restricted to NSGCT[4]. B-HCG is present in urine forming the basis of urine pregnancy tests; which may be utilised in emergency departments as a tool to help make a GCT diagnosis. This tool has also been used in austere medical environments such as in the military.[18] It has been suggested that cannabis or marijuana use spuriously elevates HCG; this is not supported by current literature. [19,20]

LDH is a less specific marker merely reflecting tumour burden as its concentration is proportional to tumour volume. It is raised in up to 80% of SGCT and 60% of NSGCT.

It is useful to assess serum testosterone levels at baseline. This may assist counselling patients if androgen supplementation is a possibility post-orchidectomy, e.g. atrophic contralateral testis. Stromal tumours typically present similarly to GCT although may also produce symptoms such as gynaecomastia reflecting endocrine dysfunction. When these signs are present luteinising hormone (LH) and follicle stimulating hormone (FSH) should also be assessed.

Testicular ultrasonography is an import adjunct to scrotal examination. It can differentiate intra- testicular from extra-testicular masses, determine the presence multiple testicular lesions and evaluate the contralateral testicle. A 7-10MHz high frequency transducer is used and the assessment should be done in at least 2 planes. SGCT are usually homogenous hypo-echoic lesion(s) occasionally replacing the entire testicle. NSGCT are often heterogeneous with poorly defined margins reflecting their mixed histology with cystic components suggesting teratomatous elements. [21]

When testicular cancer is clinically diagnosed, CT imaging of the chest/abdomen and pelvis will be required for staging purposes. This may be delayed until after surgery although chest x-ray is required prior to orchidectomy to exclude significant pulmonary metastasis.

Initial Management

Following assessment of patients with a diagnosis of clinical stage 1 an inguinal orchidectomy should be performed. This confirms the diagnosis, including local staging information and provides histological prognostic features.

Orchidectomy is a confronting prospect psychologically for the patient [22] and thus standard practice is to offer a testicular prosthesis. This can be performed concurrently at time of orchidectomy or as an interval procedure. An important caveat is for those patients known to need, or at high-risk of needing, adjuvant chemotherapy i.e. clinical stage II to IV or very high tumour markers. The risk of prosthesis-related infection is in the order of 1-2% and if it occurs, the need for its removal and antibiotics, will delay chemotherapy. Insertion of testicular prosthesis at the time of radical orchidectomy (synchronous prosthesis insertion) has been shown to be safe. [23] Dissatisfaction related to the cosmetic outcome may occur and hence more realistic expectations may be achieved if the patient is able to see samples of available prostheses.[24] Other risks associated with prosthesis insertion are extrusion (although rare when inserted through a groin incision), migration, haematoma formation and chronic pain. Concerns have been raised regarding the long-term safety of silicone based testicular implants and this has led to the development of saline filled implants. The long term safety and efficacy data on these is still unknown.[25] Organ-sparing surgery may be considered in selected patients. Currently accepted oncological indications are synchronous bilateral tumours and metachronous contralateral tumours.[26] Current EAU testicular tumour guidelines recommend that this may be considered in cases where the tumour represents <30% of the testicle. Adjuvant treatment in the form of radiotherapy delivered to the remnant testicular tissue (18-20 Gy) is used to address residual ITGCN and reduce the risk of local recurrence. [7] Irradiation at this dose affects fertility whilst preserving leydig cell function to allow normal testosterone production. [27] Testosterone replacement will be required in patients who do suffer impaired leydig cell function. Likewise, patients with an atrophic contralateral testicle may also require testosterone supplementation and it is in this sub-group of patients that organ- sparing surgery can be considered in order to try and preserve endogenous endocrine function. Irradiation following organ-sparing surgery has been shown to be effective at treating ITGCN and preventing disease relapse. [28]

Fertility is of concern to patients and must therefore be addressed. Patients with GCTs, even prior to treatment are more likely to have abnormal semen parameters.[29] Sperm banking prior to orchidectomy is not an absolute requirement but is preferable if the contralateral testis is atrophic. This should not delay oncological treatment unduly and thus these discussions should start early in the patient pathway when possible. None of the chemotherapeutic agents routinely used in the management of testicular germ cell tumours (carboplatin, bleomycin, etoposide and cisplatin) cause long term infertility when used in the first line setting. [30] Recovery usually occurs within 1-5 years although may take longer if patients have low pre-treatment sperm counts. Recovery may not occur, however, if patients have subsequent courses of chemotherapy.[30] Sperm banking should be done before chemotherapy [30] but may still be feasible up to 14 days after initiation of the first cycle. [31]

The human fertilisation and embryology authority (HFEA) is the independent body regulating human embryology and fertilisation treatment and research in the United Kingdom. Under the Human Fertilisation and Embryology Act HFEA licences and regulates clinics with a strict code of conduct to which they must adhere.[34]

Prior to sperm storage, patients should have the opportunity to discuss the process including costs and storage time limits. Currently, sperm storage for people who are about to undergo treatment likely to impair fertility is funded by the NHS based on local Clinical Commissioning Group (CCG) acceptance criteria. Patients who do not meet their local CCG criteria may self-fund as NHS patients and the currently quoted price for sperm freezing and storage for the first year is about £300. [33] The standard storage time limit is 10 years in the United Kingdom. Patients must undergo screening for infectious disease including HIV, Hepatitis B and C. They will need to provide written consent for sperm storage and will have the opportunity to detail wishes on issues such as the fate of sperm if they die or are unable to make decisions including whether partners can use the samples at a later date. Patients must understand that there is no guarantee of sperm quality after thawing and sperm may be damaged in the freezing process. There are also options for cryopreservation of testicular tissue in specialised centres as well as opportunities for sperm retrieval at the time of surgery in cases of obstructive azoospermia.

‘ Cancer patients’ are more likely than ‘infertility patients’ to use or continue storage of banked samples, [34] but even in this group utilisation of the cryopreserved sperm is low (<10%). [35] Staging

Local staging of testicular tumours is completed with histological assessment of the orchidectomy specimen. Clinical staging is determined by confirming the presence or absence of metastatic disease by cross-sectional imaging (CT chest, abdomen and pelvis) as well as post orchidectomy serum tumour markers levels. Additional imaging, including bone and/or brain is undertaken if clinically indicated based on symptoms.

GCTs metastasise in a predictable and systematic manner from the primary site to retroperitoneal lymph nodes to distant sites, most commonly lungs and posterior mediastinum. The lymphatic drainage is such that right-sided testicular tumours drain first to the inter-aortocaval region, followed by precaval and paracaval nodes. Left-sided tumours on the other hand drain to the preaortic and para-aortic lymph nodes and then to the inter-aortocaval nodes.[36] Contralateral spread (cross-over) is commonly seen for right-sided tumours but is rare for left-sided tumours. Sex cord-stromal tumours metastasise in a similar pattern. Involvement of the pelvic lymph nodes can occur either because of scrotal invasion by the primary tumour, a high-burden of retroperitoneal lymph node disease which is postulated to cause retrograde spread to the iliac node chain or in cases where the anatomical normal lymphatic drainage has been disrupted as a consequence of previous inguino-scrotal surgery such as orchidopexy for maldesceded testicle.

Staging systems commonly in clinical use include the TNM system for staging malignant disease and the Royal Marsden Hospital testicular cancer staging system which is widely used in the United Kingdom.[37] For the TNM system, “T” relates to the primary tumour after orchidectomy, “N” to the lymph node status which is determined either on clinical imaging or following pathological assessment of lymph nodes (suffix p used), and “M” relates to metastasis. For the Royal Marsden system, a stage I – IV classification is described as shown. (Table 1)

Stage 1 testicular cancers can be further classified as 1A or 1B.

 Stage 1A: Primary tumour limited to testis and epididymis. No lymphatic or vascular invasion, no metastasis. Tumour markers return to normal post orchidectomy.

 Stage 1B: Locally invasive, not metastatic

“Stage 1” disease more accurately refers to clinical stage 1 (CS1) disease based on the orchidectomy specimen, normalisation tumour markers after surgery and absence of metastatic disease on imaging. Pathological stage 1(PS1) refers to CS1 patients who undergo retroperitoneal lymph node dissection (RPLND) following orchidectomy with no histological node involvement.

Approximately 80% of SGCT and 55% of NSGCT patients present with CS1 disease.[38] These tumours are highly curable thus the need to determine which treatment options preserve the high cure rate whilst minimising harm to the patient. Table 1: Royal Marsden Staging System for Testicular Cancer

STAGE DESCRIPTION

I Confined to the testis and peritesticular tissue

IM Rising concentrations of serum tumour markers without evidence of metastatic disease

II Abdominal nodal metastasis

A <2cm

B 2-5cm

C >5cm

III Supradiaphragmatic nodal metastasis

M Mediastinal

N Supraclavicular, cervical or axillary

O No abdominal node metastasis

(Node stage as decribed for stage II above)

IV Disseminated disease

 L1 <3 metastasis

 L2 ≥3 metastasis, <2cm diameter

 L3 ≥3 metastasis, one or more >2cm diameter

H+ Liver metastasis

Br+ Brian metastasis

Bo+ Bone metastasis

Management of CS1 disease post orchidectomy

Observational studies looking at the patterns of disease relapse in CS1 disease have demonstrated high survival rates with active surveillance alone (99% 5-year disease specific survival). [39] Although surveillance, therefore, is a popular management option it is important to identify the sub-group of patients who are at increased risk of distant disease relapse and would therefore benefit from adjuvant therapy. The majority of relapses occur within 2 years for NSGCT and 3 years for SGCT.

Seminomatous germ cell tumours (SGCT) Contemporary data shows that 14% of patients with SGCT have occult metastatic disease and will relapse on surveillance.[40] For SGCT, tumour size and rete testis invasion are prognostic risk factors for identifying patients at greatest risk of relapsing. [41,42] Tumour size is a continuous variable and thus the larger the tumour size, the greater the risk of relapse. For the purposes of risk stratifying patients, a tumour size >4cm is generally accepted as the cut off for high-risk of relapse. Patients without either of the two risk factors have <3% relapse rate on surveillance as compared with 21% if risk factors are present (overall relapse rate of 14% in a non-risk stratified group). [40]

Seminoma cells are very radio-sensitive and CS1 SGCT patients have historically been treated with adjuvant retroperitoneal radiotherapy [40]. The low risk of occult metastatic disease however means that this approach is unnecessary in the vast majority of patients and yet exposes them to treatment related side effects. The risk of radiation induced secondary malignancies is an important concern. [43] Adjuvant radiotherapy is not currently recommended in the management of CS1 SGCT by the European Association of Urologists (EAU) and certainly not in patients under 40 years.[44]

For patients at high-risk of relapse, the current recommendation for adjuvant treatment is one cycle of carboplatin chemotherapy at AUC 7 based on evidence from the joint Medical Research Council (MRC) and the European Organisation for Research and Treatment of Cancer (EORTC) randomised trial of carboplatin versus radiotherapy for stage 1 seminoma.[45] The results confirmed the non- inferiority of this single dose carboplatin regimen when assessing relapse-free survival rates. There was also a significant reduction in the medium term risk of second germ cell tumours in the carboplatin arm. This approach has been confirmed by the SWENOTECA trial.[40]

Occasionally patients at low risk of recurrence may have adjuvant chemotherapy recommended. This may be prompted by concerns about compliance with, or practicality undertaking, follow-up or where if relapse occurred, standard treatment may be problematic due to comorbidities. In these circumstances it is therefore considered advantageous to reduce the risk of relapsing disease as much as possible.

Non Seminomatous Germ Cell Tumours (NSGCT)

Post orchidectomy management options for CS1 NSGCT are surveillance, adjuvant chemotherapy and RPLND. The presence of lymphovascular invasion (LVI) in the testicular tumour is the most widely accepted adverse prognostic risk factor in NSGCT. Risk of relapse with LVI is 25-50% compared to 12-15% without and thus adjuvant treatment should be considered if present. [40,46]

Standard adjuvant chemotherapy comprised two cycles of bleomycin, etoposide and cisplatin (BEP). Specific toxicity risks are associated with this regimen; Bleomycin can cause interstitial pneumonitis with subsequent pulmonary fibrosis. [47] This occurs in 10% of patients with risk factors including age (over 40), increasing dose, renal insufficiency and smoking .[48] Etoposide is associated with an increased risk of developing secondary malignancies (leukaemia) and Cisplatin is associated with hearing impairment. To minimise toxicity risks without compromising efficacy there is some evidence to support one cycle of BEP instead of two. The SWENOTECA trial reported excellent results for BEP X 1 cycle in their CS1 NSGCT cohort. They reported a relapse rate of 3.2% for high-risk patients (patients with LVI) and 1.6% for low risk patients (without LVI). [40] This new evidence has thus led to a change in EAU recommendations from 2 cycles of BEP chemotherapy to 1 cycle in the latest guideline update. [44]

Primary RPLND has been explored as an option for CS1 NSGCT with the premise of selecting out patients who are truly PS1 and also reducing the burden, cumulative radiation exposure and financial impact of imaging during follow-up. RPLND allows accurate pathological staging and thus ensures more appropriate subsequent treatment in patients found to have PS2 disease and has a potentially curative role in this cohort. The retroperitoneum is the initial and sometimes solitary site of metastatic spread and relapses in the retro-peritoneum are rare following a well performed RPLND.[36] Improvements in surgical techniques and better understanding of the patterns of lymphatic drainage in testicular tumours has meant that the morbidity associated with RPLND has greatly improved.[49] 20 - 30% of patients who have undergone RPLND are found to have retroperitoneal metastasis, upstaging them to PS2. [50] These CS1, but occult PS2 have the potential to be under-treated if surveillance is used based on a CS1 profile. Lymphovascular invasion is, however, a robust predictor of the likelihood of occult PS2 and therefore developing a ‘relapse’. [50,51] Randomised trials have additionally demonstrated that RPLND is inferior to chemotherapy at preventing recurrence in a non-risk stratified patient cohort. [52] In those patients that recurred after RPLND alone, a proportion relapsed in the retroperitonem alone, probably resulting from the use of a unilateral template only at RPLND. A significant proportion also relapsed outside of the retroperitoneum.

Based on the available evidence, surveillance is a recommended option for CS1 patients without lymphovascular invasion in the primary tumour, and where there are no concerns with compliance with follow-up. For patients at high risk of recurrence, adjuvant BEP chemotherapy is recommended. A well-defined role for RPLND in CS1 patients remains unclear.

Sex cord-stromal tumours

Approximately 10% of sex cord-stromal testicular tumours are malignant and can metastasise. [5,53] The prognostic factors associated with malignancy are size greater than 5cm, necrosis, moderate/severe nuclear atypia, angiolymphatic invasion, infiltrating margins and >3 mitotic features per 10 high power fields. [5,7] When faced with small hypo-echoic masses and where stromal tumours are suspected, an organ sparing approach should be considered if possible due to the high likelihood that these tumours are benign. Stromal tumours are relatively non responsive to chemotherapy or radiotherapy and the prognosis for patients with distant metastasis is poor. [7] RPLND, therefore, has an important role in CS1 disease when histological features associated with malignancy are present. Follow Up

Ideally follow up should identify relapse at an early stage minimising harm and burden to patients. There is currently no universal protocol for follow up of testicular cancer patients. Follow up protocols depend on the initial, and any adjuvant treatment option used and will thus differ for patients managed on surveillance, chemotherapy or primary RPLND. As follow up is risk stratified based, this can be less intense if adjuvant therapy has been employed.

There is a need for strict adherence to follow up protocols over several years and this requires significant motivation from patients. In patients with LVI, the relapse rate can be as high as 50%.

 Surveillance

90% of relapses occur within the first 2 years[7] and these occur preferentially in the retroperitoneum followed by mediastinum and the lung. The protocol recommended by the EAU guidelines is shown in table 2.[44]

Table 2: Recommended minimum follow-up schedule in a surveillance policy: stage I non- seminoma. (Reproduced with kind permission from [44])

Procedure Year

1 2 3 4-5

Physical 4 times 4 times 4 times Once/yr examination

Tumour markers 4 times 4 times 4 times Once/yr

Plain radiography of Twice chest  RPLND Abdominopelvic CT Twice Once Once (3mths, 12 mths) (24 mths) (36 mths)

The relapse rate after a well performed RPLND is rare. The recommended protocol by the EAU is similar to the surveillance policy above but CT is recommended yearly for 5 years.

 Adjuvant chemotherapy

As previously discussed, the relapse risk in these patients is very low and similar to the RPLND cohort in trials. As such the recommended follow up protocol is as per RPLND patients above.[44] The Royal Marsden Hospital’s follow up protocol is similar to that described above. There is a greater intensity of investigations in the first year with more frequent chest x-rays and serum tumour marker assessments as 80% of relapses will occur in the first year. With regards to CT imaging, only abdominal scanning is recommended unless the pelvis is deemed to be high risk (scrotal breech or previous inguinoscrotal surgery). [54]

Relapse rates depend on whether any adjuvant treatment is used. Seminoma tumours are very sensitive to chemotherapy and radiotherapy and thus relapse following adjuvant treatment is uncommon. Secondly, measurements of serum tumour markers are a less reliable means of monitoring for relapse as only 30% of seminoma patients will have elevated HCG levels at diagnosis or during treatment. [7] The EAU follow up recommendation is shown in table 3.[44]

Table 3: Recommended minimum follow-up schedule for post-orchidectomy surveillance, radiotherapy or chemotherapy: stage I seminoma. Reproduced with kind permission from [44].

Procedure Year

1 2 3-5

Physical examination 3 times 3 times Once/yr

Tumour markers 3 times 3 times Once/yr

Plain Twice Twice

Chest radiography

Abdominopelvic CT Twice Twice 36 and 60 mths

Stromal Tumours

There is little data on optimal follow up regimes for these tumours due to low numbers and the lack of follow up data in the literature.

Conclusions

Despite being an uncommon male cancer, testicular cancer remains very important in the 15-40 ages and the cure rate remains excellent irrespective of adjuvant treatment used. This therefore permits the “luxury” of controversies in what, if any, adjuvant treatment should be used, bearing in mind the need not to over-treat or overburden this group of young men with treatments that will be mostly unnecessary albeit potentially harmful.

CME Questions

1. Accepted independent risk factors for testicular GCT include the following except;

a) Cryptorchidism

b) Testicular microlithiasis

c) Affected first degree relative

d) Hypospadias

e) Low sperm counts

Answer: b. In the absence of other risk factors, testicular microlithiasis is not an independent risk factor for testicular GCT.

2. Regarding organ-sparing surgery, which of the following is untrue?

a) Adjuvant radiotherapy is used post-operatively to address ITGCN in the remnant testicular tissue.

b) Can be considered for tumours involving up to 50% of the testicle

c) May be considered in synchronous bilateral tumours.

d) Testosterone replacement may sometimes be required.

e) Patients with an atrophic contralateral testicle may require testosterone supplementation.

Answer: b; Organ sparing surgery may be considered for tumours involving <30% of the testicle.

3. Regarding Seminomatous GCT, which of the following is untrue?

a) Seminoma cells are highly radiosensitive

b) Adjuvant radiotherapy is recommended for most patients.

c) The adjuvant chemotherapy regime currently recommended is a single cycle of carboplatin. d) Tumour size and rete testis invasion are known prognostic risk factors.

e) Low risk patients with clinical stage 1 have <3% risk of recurrence with surveillance.

Answer: b. Radiotherapy is not recommended as adjuvant treatment.

4. Regarding non seminomatous germ cell tumours, which of the following is true?

a) The recommended adjuvant chemotherapy regime is 1 cycle of carboplatin.

b) Rete testis invasion is the most predictive adverse risk factor

c) NSGCT’s seldom metastasize to the retroperitoneum.

d) Adjuvant BEP (Bleomycin, etoposide and cisplatin) chemotherapy is recommended for high risk patients.

e) Low dose chemotherapy is recommended for patients without adverse risk factors.

Answer: d. The latest EAU recommendation is 1 cycle of BEP as adjuvant chemotherapy in patients with vascular invasion.

5. Regarding testicular GCT, which of the following is untrue?

a) The incidence is rising globally

b) They may contain a mixture of histological subtypes.

c) Sperm banking prior to orchidectomy is not an absolute requirement.

d) The peak incidence for seminomatous GCT is 30-40 years.

e) Cure rates overall are relatively poor.

Answer: e. Cure rates for testicular cancer are excellent.

6. In the clinical assessment of testicular tumours which of the following is true?

a) Tumour markers are rarely normal at presentation

b) Elevated LDH levels are diagnostic for non-seminomatous GCT.

c) Elevated AFP levels indicate a non-seminomatous component.

d) Chest CT is essential prior to orchidectomy.

e) Negative tumour marker results exclude a diagnosis of testicular GCT. Answer: c. Bibliography

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