Testicular Cancer

CS IA and IB

Three options, each with long-term survival approaching 100%:

• Surveillance.
• Primary RPLND.
• Primary chemotherapy (BEP×1–2) — 2019 AUA: 1 cycle for CS IA, 2 cycles for CS IB; 2010 CUA: BEP×2.

Guidelines: 2010 CUA prefers surveillance for all CS I NSGCT; 2019 AUA recommends surveillance for CS IA and all three options for CS IB. RPLND is recommended if the primary contains a secondary somatic malignancy (rhabdomyosarcoma, adenocarcinoma, or PNET).

Surveillance

Orchiectomy alone cures 70–80% of CS I NSGCT. Risk factors for relapse: predominant embryonal carcinoma (definition varies, 45–90%) and lymphovascular invasion; other factors include advanced pT stage, absence of mature teratoma, absence of yolk sac tumour, presence of EC at any percentage, MIB-1 index, tumour size, and patient age.

Protocols vary by institution: H&P and markers (AFP, hCG ± LDH) every 2–3 months (year 1), 2–4 months (year 2), 4–6 months (year 3), then 6–12 months (years 4–5); imaging (CXR + abdomen ± pelvis) every 3–6 months in year 1 (from 3 months), 4–12 months in year 2, then once in year 3 and once in year 4 or 5. Image higher-risk men (e.g. LVI) more frequently. >90% of relapses occur within the first 2 years, with late relapse (>5 years) in ~1% (seminoma, by contrast, relapses later — 10–20% of relapses occur ≥4 years out — and needs longer surveillance). Relapses are fully restaged and treated by TNM-S; early and late relapses have similar prognosis.

Primary RPLND

Performed with curative (not staging) intent in all patients. A full bilateral template dissection gives the lowest abdominopelvic recurrence (<2%) and the highest antegrade ejaculation rate (>90%) with nerve-sparing. A multicentre RCT found chemotherapy had a lower relapse rate than primary RPLND (RPLND relapse 11%, higher than other series), underscoring that RPLND should be done at experienced centres.

Primary Chemotherapy

BEP×1–2. Advantages: highest relapse-free survival of any single modality; deliverable at community centres. Disadvantages: does not treat retroperitoneal teratoma; requires long-term surveillance CT of the retroperitoneum; late-toxicity risk (no clearly safe lower limit even for 2 cycles); and chemoresistant/late-relapse potential. Relapses after primary chemotherapy are less salvageable (chemoresistant), whereas relapses after RPLND or on surveillance are chemo-naïve and cured by chemotherapy in virtually all cases.

CS IS

Elevated markers after orchiectomy without clinical/radiographic metastasis. Treat like CS IIC/III — induction chemotherapy by IGCCCG.

CS IIA and IIB

• CS IIA marker-positive, or CS IIB regardless of markers → primary chemotherapy (both CUA and AUA). CUA notes that elevated AFP/hCG or bulky nodes (>3 cm) are recurrence risks after RPLND, so these patients receive induction chemotherapy. AUA permits RPLND as an alternative for select CS IIB with normal post-orchiectomy AFP/hCG.
• CS IIA without marker elevation — a substantial proportion are over-staged; the minority upstaged to pathologic IIB may get 2 cycles of adjuvant chemotherapy. CUA: RPLND (± adjuvant chemotherapy) or surveillance with surgery for stable/growing lesions (primary chemotherapy if it becomes marker-positive). AUA: RPLND or chemotherapy.

Management after Primary RPLND (2021 NCCN / 2019 AUA)

Pathology	Management
pN0	Surveillance
pN1	Surveillance (preferred) vs chemotherapy (BEP×2 or EP×2)
pN2	Chemotherapy (BEP×2 or EP×2, preferred) vs surveillance
pN3	Chemotherapy (BEP×3 or EP×4)
pN1–3 pure teratoma	Surveillance

Immediate vs deferred chemotherapy after RPLND-proven stage II (Williams, 1987, NEJM): 2-year relapse was 6% with immediate vs 49% with deferred chemotherapy, but with no significant difference in cancer-specific or overall survival.

Growing Teratoma Syndrome

Teratoma is chemoresistant, so RPLND is preferred as initial therapy for patients at risk of retroperitoneal teratoma but low systemic risk (normal markers, lymphadenopathy <3 cm) — unresected teratoma can grow rapidly, transform into malignancy, or relapse late. Suspect growing teratoma syndrome when markers decline as expected during chemotherapy but masses (often cystic) enlarge radiologically. Management: complete the full chemotherapy course and resect the growing/residual masses afterward; rarely, rapid progression despite falling markers requires resection before chemotherapy is finished. Complete resection carries a favourable long-term prognosis.

CS IIC and III

Induction cisplatin-based chemotherapy by IGCCCG:

• Good-risk: BEP×3 or EP×4 (5-year OS 91–94%).
• Intermediate/poor-risk: BEP×4 (5-year OS 79% intermediate, 48% poor).
• VIP×4 may replace BEP×4 with compromised pulmonary function or when extensive chest surgery for residual disease is anticipated.

Post-chemotherapy Residual Masses (PC-RPLND)

After first-line chemotherapy, 5–15% have a partial response with positive markers or progression.

• Markers elevated after induction → salvage chemotherapy.
• Markers normal, residual >1 cm → resection (full bilateral template RPLND if retroperitoneal). Residual <1 cm → controversial.

PC-RPLND histology: necrosis/fibrosis ≈40%, teratoma ≈45%, viable malignancy ≈15% (6–8% harbour non-GCT malignancy from teratoma transformation). Necrosis cannot be predicted reliably enough to skip surgery, though pure EC in the primary is the best predictor of fibrosis-only. Long-term survival is ~90% with fibrosis/teratoma only vs 50–70% with viable GCT. Management by PC-RPLND pathology (2021 NCCN): teratoma or necrosis/fibrosis → surveillance; viable disease (EC, yolk sac, choriocarcinoma, seminoma) → 2 cycles of chemotherapy (EP, TIP, VIP, or VeIP).

FDG-PET has no role in assessing NSGCT residual masses. With residual disease at multiple sites (retroperitoneum, chest, left supraclavicular fossa most common) and normal markers, resect all measurable disease — RPLND first, because retroperitoneal disease is most probable and its histology predicts the other sites (if the retroperitoneum is clear, other sites are unlikely involved). If RPLND shows viable malignancy → chemotherapy; fibrosis → surveillance or resection; teratoma → resection.

Relapse & Scrotal Exploration

Relapse management depends on prior treatment and location:

• Chemo-naïve → first-line chemotherapy by IGCCCG (cure >95%). Select CS I surveillance patients relapsing in the retroperitoneum with non-bulky (<3 cm) disease and normal markers may receive induction chemotherapy or RPLND (especially if teratoma was in the primary).
• Relapse after chemotherapy → salvage chemotherapy; resect residual masses after a serologic complete response. Viable malignancy in post-salvage specimens carries a poor prognosis not improved by postoperative chemotherapy. Late relapse is chemoresistant — outcome depends on complete surgical resection.

Scrotal exploration revealing NSGCT requires further treatment: low-stage → wide excision of the scrotal scar and removal of the spermatic cord; high-stage → systemic therapy is given, so hemiscrotectomy is unnecessary.

Self-Test

1. What two pathologic features most predict relapse of CS I NSGCT on surveillance? Predominant embryonal carcinoma and lymphovascular invasion.

2. What does a full bilateral template primary RPLND achieve in CS I NSGCT? Abdominopelvic recurrence <2% and antegrade ejaculation >90% (with nerve-sparing).

3. How is pathologic stage II managed after primary RPLND by node status? pN0 → surveillance; pN1 → surveillance (preferred) or BEP/EP×2; pN2 → chemotherapy preferred; pN3 → BEP×3/EP×4; pure teratoma (any pN) → surveillance.

4. What is the histologic distribution at PC-RPLND, and what does viable disease mandate? ~40% necrosis/fibrosis, ~45% teratoma, ~15% viable; viable disease warrants 2 cycles of chemotherapy (EP/TIP/VIP/VeIP).

5. Why is RPLND preferred over chemotherapy when retroperitoneal teratoma is suspected with low systemic risk? Teratoma is chemoresistant and, if unresected, can grow (growing teratoma syndrome), transform into malignancy, or relapse late.