Treatment-related Sequelae
Early toxicity:
- Chemotherapy — cisplatin: fatigue, myelosuppression, infection, peripheral neuropathy, hearing loss, diminished renal function, and death; etoposide: myelosuppression.
- Radiation — fatigue, nausea/vomiting, leukopenia, dyspepsia.
Late toxicity:
- Hypogonadism — occurs in 10–20% after orchiectomy alone, 15–40% after radiation, and 20–25% after first-line chemotherapy. Measure AM testosterone and LH if symptomatic.
- Infertility — most men can father children, but paternity rates are lower after radiation and/or chemotherapy.
- Cardiovascular disease and secondary malignancy — both increased by subdiaphragmatic radiation or platinum-based chemotherapy; ensure primary-care follow-up for modifiable risk factors and appropriate cancer screening.
Chemotherapy-specific:
- Bleomycin — pulmonary complications (including pulmonary fibrosis), Raynaud phenomenon, mild myelosuppression at high doses.
- Cisplatin — nephrotoxicity, neurotoxicity, peripheral neuropathy, hearing loss.
Brain Metastases
Associated with choriocarcinoma — suspect in any patient with a very high serum hCG. Choriocarcinomas are highly vascular and tend to hemorrhage during chemotherapy, with death rates of 4–10% from intracranial hemorrhage.
- At diagnosis: BEP×4, then resection of residual masses.
- Brain relapse after first-line chemotherapy: second-line chemotherapy, then resection and/or radiotherapy.
- Brain relapse after a complete response carries a worse prognosis than brain involvement present at diagnosis.
Primary Extra-gonadal GCT
95% of GCTs are gonadal and 5% extra-gonadal, arising in midline locations — in descending frequency: mediastinum, retroperitoneum, sacrococcygeal region, and pineal gland.
- Primary mediastinal NSGCT (vs testicular/retroperitoneal NSGCT) more often has yolk sac components with elevated AFP, is associated with Klinefelter syndrome, is less chemosensitive, and carries a poor prognosis.
- Primary mediastinal seminoma has a prognosis similar to testicular seminoma.
- Primary retroperitoneal GCT behaves like, and carries the same prognosis as, testicular GCT.
Of patients with metastatic GCT and no testis mass, one-third each have: a true extra-gonadal primary, ITGCN in the testis, or sonographic evidence of a "burned-out" primary.
Diagnosis: consider GCT for any midline mass in a male <40. With elevated AFP and/or hCG, the diagnosis is established even if the testis is normal — no biopsy is needed before treatment; with normal markers, biopsy the midline mass to confirm first.
Inguinal orchiectomy is indicated in suspected extra-gonadal GCT when the metastatic pattern matches a right- or left-sided testicular primary, or there is a sonographic burned-out primary.
Small Impalpable Testicular Lesions
Small (<10 mm), impalpable intratesticular lesions without disseminated GCT or elevated markers are a diagnostic dilemma — most are benign (testicular cysts, small infarcts, small Leydig or Sertoli cell tumours), but 20–50% are small GCTs (usually seminoma), with malignancy risk rising with lesion size. Three options:
- Inguinal orchiectomy.
- Testis-sparing surgery — inguinal exploration and excision with frozen section to exclude GCT (intraoperative ultrasonography helps localize the lesion).
- Close observation with serial ultrasound, exploring any growing lesion.
Self-Test
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Which subtypes comprise non-seminoma germ cell tumours? Embryonal carcinoma, choriocarcinoma, yolk sac tumour, and teratoma — alone or mixed. Any tumour containing these elements (even alongside seminoma) is classified as NSGCT.
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What percentage of patients have metastatic disease at diagnosis? ~33% of NSGCT and ~15% of pure seminoma.
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Which tumours secrete AFP and hCG, and what are their half-lives? AFP — yolk sac, EC, teratoma (half-life 5–7 days). hCG — seminoma (~15%), EC, choriocarcinoma (half-life 24–36 hours).
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What is the primary landing zone for a left vs right testicular tumour? Left → para-aortic nodes (then inter-aortocaval). Right → inter-aortocaval nodes (then paracaval/para-aortic).
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How is a post-chemotherapy retroperitoneal mass managed? Elevated markers → salvage chemotherapy. Normal markers: in NSGCT, resect a mass >1 cm by full bilateral template RPLND; in seminoma, use FDG-PET for masses >3 cm (positive → surgery) and observe masses <3 cm.