21st June 2023

Testicular cancer

Testicular cancer presents with a bimodal age distribution with peaks aged between 15-35 for tumours arising from germ-cell origins including teratoma, whereas seminoma, which arises from the germinal epithelium of the seminiferous tubules, typically presents over the age of 35. Patients typically present with a testicular mass, pain or features of distant disease including back pain, fevers, and weight loss. The incidence of testicular cancer has been increasing since the 1990s, however, the aetiology of this is unclear.

Tumour markers in germ-cell tumours include beta-HCG, alpha-fetoprotein and LDH and are useful in their diagnosis and prognostication. Importantly, AFP is never raised in seminoma. (Please note in the exam, to be wary of answers that include the key phrases ‘never’ and ‘always’ as they are usually incorrect; little in Medicine is black and white). If AFP is elevated in the context of a known seminoma, consider whether there is dual pathology or a misdiagnosis. Other causes of a raised AFP can include hepatocellular carcinoma, cirrhosis, and hepatitis. If no alternative cause for the AFP rise is found, there is likely incomplete/incorrect histological diagnosis and so this malignancy should be treated as a non-seminomatous germ-cell tumour (NSGCT), where mixed pathology is likely to be present. The treatment differs depending on whether the germ-cell tumour is seminomatous or non-seminomatous.

Management of the primary cancer is typically with a radical orchidectomy, and further adjuvant treatment is based on tumour markers and histological features. Surveillance versus adjuvant chemotherapy is considered for early disease. Lymph-node positive and metastatic disease is typically treated with chemotherapy initially, prior to orchidectomy (unless distant disease is identified after the initial surgery). Chemotherapy regimens for advanced disease typically involve bleomycin, epirubicin and cisplatin (shortened to BEP). Even in patients with metastatic disease, cure rates remain >90%.

Although it is unfair to expect a working understanding of the practicalities and side effects of chemotherapy, these questions do arise. There are common tropes with certain chemotherapy agents. Some of these are listed below, please note not all of these agents will be employed in germ-cell tumours:

• Platinums (e.g. cisplatin, carboplatin and oxaliplatin): Notable side effects include neutropenia, nausea, ototoxicity, nephrotoxicity, peripheral neuropathy, and venous thrombo-embolic disease.
• Bleomycin: Notably causes ‘bleomycin lung’ which can manifest as profound pulmonary fibrosis, which can be devastating in such a young population. The risk of pneumonitis is increased in those older than 40, with pre-existing pulmonary disease, renal impairment or undergoing high-flow oxygen therapy.
• Alkylating agents (e.g. cyclophosphamide, ifosfamide, temozolomide): Notable side effects include alopecia, neutropenia (+/- pancytopenia) & diarrhoea.
• Antimetabolite agents – this is a diverse group of agents, targeting metabolites of DNA/RNA synthesis
  • Capecitabine or 5-fluorouracil: Notable risks include profound, life-threatening diarrhoea, palmar-plantar erythrodysesthesia (PPE) and coronary artery vasospasm, particularly in the presence of pre-existing dihydropyrimidine dehydrogenase deficiency (DPD).
  • Methotrexate: Associated with pancytopenia, pulmonary fibrosis, hepatotoxicity, nephropathy