Seminoma

Seminoma is a germ cell tumour made of uniform cells resembling primordial germ cells, and it is the commonest pure testicular germ cell tumour, making up about 50% of germ cell tumours. It arises from germ cell neoplasia in situ.

Peak age is 30 to 45 years, about 10 years later than for nonseminomatous tumours. About 80% present with disease confined to the testis, and cure rates exceed 95% overall because it is highly sensitive to platinum chemotherapy and to radiotherapy.

Pathophysiology. Risk factors: cryptorchidism (relative risk 2 to 8), previous germ cell tumour (about 2% risk in the other testis), a brother or father with testicular cancer (risk 8 to 10 times and 4 to 6 times higher), infertility, Klinefelter syndrome (mainly extragonadal) and testicular atrophy.

All germ cell tumours carry the isochromosome 12p. Seminoma cells are positive for OCT3/4, placental alkaline phosphatase, CD117 and D2-40, and negative for CD30 and AFP.

Spread is mainly by lymphatics to retroperitoneal nodes, then mediastinal and supraclavicular nodes, and later to lung, liver, bone and brain.

Stage:

• Stage I: confined to the testis.
• Stage IIA, IIB, IIC: retroperitoneal nodes of 2 cm or less, over 2 to 5 cm, and over 5 cm.
• Stage III: supradiaphragmatic nodes or distant metastases.

Spermatocytic tumour is a separate entity in older men with no germ cell neoplasia in situ and a benign course.

A painless testicular lump or heaviness, found by the patient or partner, and sometimes a dull ache. About 10% present with acute pain. Metastatic disease causes back pain from nodes, cough, dyspnoea, a neck mass, leg swelling or gynaecomastia (from hCG). Raised beta-hCG occurs in about 10 to 20%.

A scrotal mass is cancer until proven otherwise. Do not do a scrotal biopsy or scrotal incision.

• Scrotal ultrasound of both testes: a homogeneous, hypoechoic, well circumscribed mass, with microlithiasis in some.
• Serum AFP, beta-hCG and lactate dehydrogenase before orchidectomy. AFP is normal in pure seminoma, and a raised AFP means a nonseminomatous component and is managed as such. Repeat after orchidectomy (AFP half life 5 to 7 days, beta-hCG about 24 to 36 hours).
• CT of chest, abdomen and pelvis with contrast after orchidectomy for staging. MRI of the brain and bone scan only for symptoms.
• Pathology: histology with immunostaining, tumour size, rete testis involvement, lymphovascular invasion, germ cell neoplasia in situ and pT stage.
• Risk groups in advanced disease: good (any site, no non-pulmonary visceral metastases) and intermediate (non-pulmonary visceral metastases). There is no poor risk group. Five year survival is about 90% (good) and about 80% (intermediate).
• Before treatment: semen analysis and testosterone, HIV and hepatitis tests, creatinine clearance, audiometry and lung function when chemotherapy is planned.

Differential diagnosis.

• Nonseminomatous germ cell tumour
• Testicular lymphoma
• Leydig cell tumour or Sertoli cell tumour
• Epididymo orchitis or abscess
• Haematoma or infarct
• Testicular adrenal rest tumour
• Spermatocytic tumour

• Offer sperm banking before orchidectomy or any treatment.
• Radical inguinal orchidectomy with high ligation of the cord at the internal ring. Testis sparing surgery for a small mass in selected men (solitary testis or bilateral tumours). Offer a testicular prosthesis.
• Stage I (surveillance, carboplatin or radiotherapy):
  • Surveillance is preferred when reliable, with relapse in about 15 to 20% (risk factors: size over 4 cm and rete testis invasion), almost all curable.
  • Single dose carboplatin at AUC 7 (dose in mg equals AUC multiplied by GFR plus 25, with measured GFR) lowers relapse to about 5%.
  • Radiotherapy 20 Gy to the para aortic nodes lowers relapse to about 4% but carries a risk of secondary cancer, so it is used less often.
• Stage IIA: radiotherapy 30 Gy to the para aortic and ipsilateral iliac nodes, or BEP for 3 cycles. Stage IIB: radiotherapy 36 Gy, or BEP for 3 cycles or EP for 4 cycles.
• Stage IIC and III, and good risk: BEP for 3 cycles or EP for 4 cycles. Intermediate risk: BEP for 4 cycles (or VIP for 4 cycles when bleomycin is contraindicated).
  • BEP is repeated every 21 days: bleomycin 30 units intravenously on days 1, 8 and 15, etoposide 100 mg/m2 intravenously on days 1 to 5, and cisplatin 20 mg/m2 intravenously on days 1 to 5 with hydration (1 to 2 L of saline before and after, with magnesium and potassium replacement).
  • EP is the same without bleomycin.
  • Antiemetics for high emetic risk: a 5-HT3 antagonist (ondansetron 8 mg), dexamethasone 12 mg, and aprepitant 125 mg on day 1, then aprepitant 80 mg on days 2 and 3 with dexamethasone 8 mg on days 2 to 4.
  • Check full blood count, creatinine clearance (cisplatin needs over 60 mL/min), magnesium and liver tests before each cycle. Do not reduce doses for neutropenia. Neutropenic fever is an emergency, needing intravenous antibiotics within 60 minutes.
  • Bleomycin cautions: lung toxicity (stop for cough, dyspnoea or falling carbon monoxide transfer factor), age over 40, smoking, and eGFR under 60. Limit inspired oxygen during anaesthesia.
• Residual mass over 3 cm after chemotherapy: PET-CT at least 6 weeks after the last cycle. A positive scan leads to biopsy or resection, and a negative scan to observation.
• Relapse after first line treatment: salvage chemotherapy with TIP or VeIP, or high dose carboplatin and etoposide with autologous stem cell rescue, at a specialist centre.
• Late effects: hearing loss, neuropathy, kidney injury, Raynaud, secondary leukaemia and solid cancers, cardiovascular disease, hypogonadism and infertility. Recovery of sperm production occurs in many men within 2 to 5 years.

Monitoring. Stage I surveillance: clinical review and CT abdomen and pelvis at 6 and 12 months, then yearly to 3 to 5 years. After treatment: markers, clinical review and imaging every 3 to 6 months for 2 years, then yearly for 5 years. Testosterone and lipids yearly. Testicular self-examination for the remaining testis.

Referral and escalation. Refer to urology for any suspected mass, and to oncology for staging and chemotherapy. Urgent referral for metastatic symptoms, very high hCG or neutropenic fever.