Testicular Cancer

General Principles

• Any post-pubertal male, regardless of age, is treated by adult guidelines.
• Manage in a multidisciplinary setting (urology, medical oncology, radiation oncology, pathology, radiology). Expert pathology review is recommended and changes the subtype in 1–4% of cases.
• Base decisions on imaging within the preceding 4 weeks and serum markers (hCG, AFP) within 10 days. Because GCTs (especially NSGCT) grow rapidly, risk-adapted decisions (e.g. RPLND for stage IIA) must use recent studies to avoid undertreatment.
• With normal markers and equivocal imaging, repeat imaging in 6–8 weeks before recommending treatment.

Pre-treatment Counselling

Before definitive treatment, counsel on three risks:

• Hypogonadism — over long-term follow-up, 10–15% develop low serum testosterone or require replacement. (In long-term survivors, testosterone is similar to controls but age-adjusted LH is higher — Nord, 2003.)
• Infertility — at diagnosis up to 50% have impaired semen parameters and 10% are azoospermic. Offer sperm cryopreservation: pre-orchiectomy if there is no normal contralateral testis or known subfertility; post-orchiectomy before any further (non-orchiectomy) treatment in those undecided or planning paternity. Nearly all men become azoospermic after chemotherapy, and 50–80% recover baseline parameters within 2 and 5 years respectively; recovery after seminoma radiotherapy may take 2–3 years or longer.
• Contralateral tumour — the risk of a second primary in the contralateral testis, though rare, is significantly increased.

Orchiectomy & Testis-Sparing Surgery

Radical inguinal orchiectomy is the standard — remove the testicle and spermatic cord to the internal inguinal ring; discuss a testicular prosthesis beforehand. (See the radical orchiectomy procedure page for operative detail.)

• Trans-scrotal orchiectomy is contraindicated (scrotal violation). If it has been performed for malignancy, counsel on the increased local-recurrence risk; adjunctive scar excision or radiotherapy is rarely needed, and after systemic therapy local relapse is rare and no adjuvant is required.
• In the rare case of a possibly benign tumour, perform excisional biopsy with frozen section before definitive orchiectomy to permit organ-sparing partial orchiectomy.
• Timing: orchiectomy precedes other treatment — except with life-threatening metastatic disease and unequivocally elevated AFP/hCG, where chemotherapy starts first and orchiectomy is deferred.

Testis-sparing surgery (TSS) is not recommended for a suspicious lesion with a normal contralateral testis (do radical orchiectomy). Indications: a patient wishing to preserve gonadal function with a mass <2 cm and one of — equivocal US/exam with negative markers; a congenital, acquired, or functionally solitary testis; or bilateral synchronous tumours. Counsel on higher local recurrence, the need for exam/US monitoring, the role and gonadal toxicity of adjuvant testicular radiotherapy, and risks of atrophy/TRT/subfertility. Take multiple biopsies of normal ipsilateral parenchyma to exclude GCNIS — 50–80% of TSS patients have concomitant GCNIS.

GCNIS Management

Treatment is justified by the high risk of progression to invasive GCT (≈50% at 5 years). GCNIS is diagnosed on biopsy (infertility workup, contralateral biopsy in a GCT patient, or within the affected testis during TSS).

Options: orchiectomy; low-dose radiotherapy (18–20 Gy); or close observation.

• If the patient prioritizes fertility/androgen production → surveillance (periodic US, deferring therapy until pregnancy is achieved and/or GCT develops; reasonable when semen is adequate for ART).
• If the patient prioritizes cancer-risk reduction → testicular radiotherapy (18–20 Gy) or orchiectomy.
• Radiation spares endocrine function more than orchiectomy (Leydig cells are radioresistant relative to germinal epithelium), but Leydig function declines over time and 40% later need supplemental testosterone; it causes permanent sterility of the treated testis (can be delayed for men wanting children). For a normal contralateral testis with a desire for paternity, radical orchiectomy is preferred because radiation scatter can impair contralateral spermatogenesis.
• If GCNIS is not found on biopsy, it is likely present in unsampled tissue — follow with self-exam, US, and markers; any ipsilateral local recurrence warrants completion radical orchiectomy. An open inguinal contralateral biopsy may be considered with risk factors or suspicious US.

Delayed orchiectomy: in widespread/symptomatic disease diagnosed by metastatic biopsy or empirically, systemic chemotherapy supersedes diagnostic orchiectomy; because of discordant intratesticular response, delayed orchiectomy is recommended for all NSGCT after induction chemotherapy — even with a complete retroperitoneal response. Its role is more controversial in presumed extra-gonadal GCT (favoured when retroperitoneal disease lateralizes to the expected testicular drainage).

Post-orchiectomy Principles

Subsequent management depends on histology (seminoma vs NSGCT) and clinical stage. Newly elevated or rising markers after orchiectomy indicate metastatic disease → induction chemotherapy. With a negative metastatic workup and slowly declining markers (not by half-life), monitor closely and recheck until levels normalize or begin to rise.

Treatment Modalities

Surveillance (Clinical Stage I)

Orchiectomy alone cures 80–85% of CS I seminoma and 70–80% of CS I NSGCT, and relapses are salvaged with excellent outcomes — so surveillance minimizes treatment-related toxicity by restricting therapy to those with proven need. Trade-offs: the highest relapse rate (vs adjuvant therapy), the need for long-term (>5 years) surveillance, second-malignancy risk from intensive CT imaging, and more intensive therapy if relapse occurs.

Radiotherapy

Seminoma is radiosensitive. Radiotherapy has no role in NSGCT, except for brain metastases.

Chemotherapy & IGCCCG Risk Classification

The IGCCCG risk classification (good / intermediate / poor) — not TNM — selects the chemotherapy regimen and number of cycles in advanced disease. It was developed for metastatic-at-diagnosis patients and does not apply to relapsed disease. NSGCT is classified by non-pulmonary visceral metastasis, primary mediastinal site, and marker levels at the start of chemotherapy (not pre-orchiectomy). Seminoma is classified by non-pulmonary visceral metastasis only and has no poor-prognosis category.

Histology	Good	Intermediate	Poor
Non-seminoma	Testis/retroperitoneal primary, no non-pulmonary visceral mets, and good markers (AFP <1,000 ng/mL, hCG <5,000 IU/L, LDH <1.5× ULN)	Testis/retroperitoneal primary, no non-pulmonary visceral mets, and intermediate markers (AFP 1,000–10,000, or hCG 5,000–50,000 IU/L, or LDH 1.5–10× ULN)	Mediastinal primary, or non-pulmonary visceral mets, or poor markers (AFP >10,000 ng/mL, or hCG >50,000 IU/L, or LDH >10× ULN)
Seminoma	Any primary site, no non-pulmonary visceral mets, normal AFP (any hCG/LDH)	Any primary site, with non-pulmonary visceral mets, normal AFP (any hCG/LDH)	— (none)

During chemotherapy, monitor with serial markers; afterward, radiologically restage all patients. If markers decline as expected, treat any residual mass appropriately; if they plateau at a low level, follow closely. Markedly elevated pre-treatment hCG may take longer to normalize or plateau.

Self-Test

1. How current must imaging and markers be for management decisions? Imaging within 4 weeks and serum hCG/AFP within 10 days — GCTs grow fast, so stale studies risk undertreatment.

2. What are the cure rates of orchiectomy alone in CS I disease? 80–85% for CS I seminoma and 70–80% for CS I NSGCT; relapses on surveillance are salvageable.

3. What are the indications for testis-sparing surgery? A wish to preserve gonadal function with a mass <2 cm plus one of: equivocal US/exam with negative markers, a solitary testis, or bilateral synchronous tumours — not for a suspicious lesion with a normal contralateral testis.

4. Why is delayed orchiectomy recommended for all NSGCT after induction chemotherapy? Intratesticular response is discordant from the retroperitoneum, so viable tumour or teratoma may persist in the testis even after a complete retroperitoneal response.

5. What factors define the IGCCCG groups, and which histology has no poor-prognosis category? Primary site, non-pulmonary visceral metastasis, and marker levels at chemotherapy initiation; seminoma has no poor-prognosis category.