What is the recommended management for an adult male with an intra‑abdominal (undescended) testicular germ‑cell tumor and an unresectable para‑aortic mass?

Management of Intra-Abdominal Testicular Cancer with Unresectable Para-Aortic Mass

Primary cisplatin-based chemotherapy is the definitive treatment for intra-abdominal (undescended) testicular germ cell tumors with unresectable para-aortic masses, with the specific regimen and number of cycles determined by tumor histology (seminoma vs. nonseminoma), serum tumor markers (AFP, β-hCG, LDH), and IGCCCG risk stratification. 1

Immediate Pre-Treatment Steps

Diagnostic Confirmation and Staging

• Obtain serum tumor markers (AFP, β-hCG, LDH) immediately to establish baseline values for risk stratification and to differentiate seminoma from nonseminoma (AFP must be normal for pure seminoma diagnosis) 1
• Perform CT chest, abdomen, and pelvis to fully stage disease and assess extent of retroperitoneal involvement 1
• Consider fine needle aspiration cytology of the abdominal testicular mass if tissue diagnosis is needed before initiating chemotherapy, particularly when clinical presentation is atypical 2
• Offer sperm cryopreservation before chemotherapy as cisplatin-based regimens cause permanent infertility in many patients 1, 3

Risk Stratification Using IGCCCG Classification

Apply the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification using nadir post-orchiectomy marker levels (or pre-chemotherapy levels if orchiectomy is deferred), primary tumor site, presence of nonpulmonary visceral metastases, and histology 1, 4

For nonseminomatous germ cell tumors (NSGCT):

• Good risk: AFP <1,000 ng/mL, β-hCG <5,000 IU/L, LDH <1.5× ULN, no nonpulmonary visceral metastases, testis/retroperitoneal primary (5-year survival 92%) 1
• Intermediate risk: AFP 1,000-10,000 ng/mL OR β-hCG 5,000-50,000 IU/L OR LDH 1.5-10× ULN, no nonpulmonary visceral metastases (5-year survival 80%) 1
• Poor risk: AFP ≥10,000 ng/mL OR β-hCG ≥50,000 IU/L OR LDH ≥10× ULN OR mediastinal primary OR nonpulmonary visceral metastases (5-year survival 48%) 1

For seminomas:

• Good risk: Any marker levels, no nonpulmonary visceral metastases (5-year survival 86%) 1
• Intermediate risk: Any marker levels, nonpulmonary visceral metastases present (5-year survival 72%) 1

Primary Chemotherapy Regimens

For Good-Risk Disease (Seminoma or NSGCT)

Administer 3 cycles of BEP (bleomycin, etoposide, cisplatin) as the standard regimen 1, 4:

• Bleomycin 30,000 IU on days 1,8, and 15
• Etoposide 100 mg/m² on days 1-5
• Cisplatin 20 mg/m² on days 1-5 (or 50 mg/m² on days 1-2) 1

Alternative: 4 cycles of EP (etoposide, cisplatin) if bleomycin is contraindicated due to poor lung function or older age (risk of pneumonitis) 1, 4

For Intermediate-Risk Disease

Administer 4 cycles of BEP as the standard approach 1, 4

For Poor-Risk Disease

Administer 4 cycles of BEP at 21-day intervals without dose reduction or delay 1, 4

Critical Chemotherapy Management Points

• Monitor serum tumor markers before each cycle to assess response; insufficient marker decline between cycles indicates poor prognosis and may require treatment modification 1, 4
• If markers rise between day 1 of cycle 1 and day 1 of cycle 2, repeat markers midway through cycle 2 to determine if decline has begun 1
• Assess renal function (creatinine, BUN, creatinine clearance) and electrolytes (magnesium, sodium, potassium, calcium) before each cycle due to cumulative cisplatin nephrotoxicity 3, 5
• Administer chemotherapy at 21-day intervals without delays or dose reductions whenever possible, as this significantly impacts cure rates 3, 4

Timing of Orchiectomy

Defer orchiectomy until after completion of induction chemotherapy in patients with bulky unresectable retroperitoneal disease 2. This approach:

• Avoids difficult surgical removal of the primary tumor when bulky metastases are present
• Allows for one-stage surgical removal of both the primary tumor and residual metastases after chemotherapy
• Improves compliance and decreases loss to follow-up 2

Perform abdominal orchiectomy via inguinal approach after chemotherapy completion along with assessment of residual masses 2

Post-Chemotherapy Management

For Seminomas with Residual Masses

• If residual mass >3 cm with normal markers: Consider surveillance or radiotherapy (category 2B) 1
• If residual mass ≤3 cm with normal markers: Surveillance is appropriate 1
• If progressive disease (growing mass or rising markers): Treat with second-line chemotherapy 1

For NSGCT with Residual Masses

• If residual mass present after chemotherapy and markers are normal: Perform retroperitoneal lymph node dissection (RPLND) if technically feasible 1, 6
• Complete surgical resection is critical as 8.5% of elective post-chemotherapy RPLND specimens contain undifferentiated malignant teratoma, 66% contain differentiated teratoma, and only 25% show necrosis/fibrosis 6
• Incomplete resection significantly worsens survival, particularly in the salvage setting 6

Important Anatomic Consideration

Be aware that 41% of patients with intra-abdominal undescended testis have atypically altered ilioinguinal metastases requiring modification of radiotherapy ports and/or RPLND boundaries 2

Salvage Treatment for Refractory or Relapsed Disease

For patients with progressive disease after first-line chemotherapy or incomplete response:

• Favorable prognostic factors (testicular primary, prior complete response, low markers, low-volume disease): Consider conventional-dose second-line chemotherapy with TIP (paclitaxel, ifosfamide, cisplatin) or VeIP (vinblastine, ifosfamide, cisplatin) 1, 4
• Unfavorable prognostic factors (incomplete response, high markers, high-volume disease, extragonadal primary): Consider high-dose chemotherapy with autologous stem cell transplant 1, 4

Prognosis Considerations

Survival outcomes differ significantly by histology in intra-abdominal testicular tumors with bulky metastases:

• Seminomas: 86% actuarial survival with primary chemotherapy followed by orchiectomy ± radiotherapy for partial responders 2
• NSGCT: 39% actuarial survival, with tumor histology (not initial stage) being the most significant prognostic parameter on multivariate analysis 2

Post-chemotherapy orchiectomy specimens show viable tumor in 61.5% of cases, emphasizing the importance of surgical removal even after chemotherapy 2