What is the initial treatment recommendation for a patient with testicular germ cell tumor (TGCT) and lung metastasis?

Treatment of Testicular Germ Cell Tumor with Lung Metastasis

Patients with testicular germ cell tumors and lung metastases should receive urgent cisplatin-based combination chemotherapy (BEP regimen) as initial treatment, with the number of cycles determined by IGCCCG risk stratification. 1

Immediate Diagnostic Approach

In patients with extensive lung metastases, chemotherapy may be initiated based on clinical presentation and elevated tumor markers (AFP and β-HCG) alone, without waiting for orchiectomy histology. 1 This approach is critical when disease burden is life-threatening, as delays can worsen outcomes. Orchiectomy can be performed after chemotherapy completion. 2

For patients who are stable enough for orchiectomy first:

• Radical inguinal orchiectomy provides definitive histologic diagnosis and is both diagnostic and therapeutic 3
• Serum tumor markers (AFP, β-HCG, LDH) must be drawn before orchiectomy and repeated at 7 days post-operatively to assess half-life kinetics 2

Mandatory Staging Workup

Before initiating chemotherapy, complete the following:

• CT chest, abdomen, and pelvis to define extent of pulmonary and nodal disease 2
• Brain MRI (or CT if MRI unavailable) if β-HCG >10,000 IU/L or >10 lung metastases present, as these indicate high CNS involvement risk 1, 2
• Bone scan if alkaline phosphatase elevated or bone symptoms present 1, 2
• Complete blood count, renal function (creatinine, BUN), liver function tests, and electrolytes (magnesium, sodium, potassium, calcium) as baseline for chemotherapy dosing and toxicity monitoring 2, 4

IGCCCG Risk Stratification

Establish the IGCCCG prognostic group immediately, as this directly determines chemotherapy intensity: 2, 3

For Non-Seminomatous Germ Cell Tumors:

• Good prognosis: BEP × 3 cycles 3, 5
• Intermediate or poor prognosis: BEP × 4 cycles 3, 5

For Seminoma:

• Good prognosis: normal AFP, any HCG/LDH, no nonpulmonary visceral metastases 2
• Intermediate prognosis: normal AFP, any HCG/LDH, with nonpulmonary visceral metastases 2

The BEP regimen consists of bleomycin, etoposide, and cisplatin (also called PEB). 4, 6, 7 Cisplatin is FDA-approved for metastatic testicular tumors in established combination therapy. 4

Chemotherapy Administration

Cisplatin-based chemotherapy should not be given more frequently than once every 3-4 weeks due to cumulative nephrotoxicity. 4 Monitor serum creatinine, BUN, creatinine clearance, and electrolytes (magnesium, sodium, potassium, calcium) before each cycle. 4

Critical contraindications to cisplatin include:

• Pre-existing renal impairment 4
• Myelosuppression 4
• Hearing impairment (cisplatin causes cumulative ototoxicity) 4

Audiometric testing should be performed before initiating therapy and before each subsequent dose. 4

Post-Chemotherapy Management

After chemotherapy completion, tumor marker measurement and repeat CT scans are mandatory to assess response. 1

For patients with residual masses post-chemotherapy:

• Non-seminomatous GCT: Surgical resection of all residual masses is mandatory when tumor markers normalize, as imaging cannot reliably distinguish necrosis from viable tumor or teratoma 1, 6, 7, 8
• Seminoma: Surgery required only if residual mass is bulky (≥3 cm) or PET-positive 7, 8

Resection should be performed by a specialist surgeon experienced in retroperitoneal and thoracic procedures. 1, 7 For pulmonary metastases, complete surgical resection of all residual lung nodules provides accurate response assessment and removes any viable tumor. 6, 8

Pre-Treatment Counseling

Offer sperm cryopreservation before chemotherapy or radiotherapy, as these treatments impair fertility. 1, 3 This should be done urgently but should not delay life-saving chemotherapy in critically ill patients.

Expected Outcomes

With appropriate treatment, cure rates are excellent:

• Stage I: 99% 5-year survival 3, 9
• Stage II: 92% 5-year survival 3, 9
• Stage III: 85% 5-year survival 3, 9
• Overall cure rate with metastatic disease: 70-90% achieve durable remission 5, 7

Common Pitfalls to Avoid

• Do not delay chemotherapy in patients with extensive lung metastases waiting for orchiectomy—start treatment based on markers and clinical picture 1
• Do not use scrotal approach for orchiectomy—this increases local recurrence rates; always use inguinal approach 3
• Do not skip post-chemotherapy surgical resection of residual masses in NSGCT with normalized markers—imaging cannot determine histology, and viable tumor or teratoma may be present 6, 7, 8
• Do not administer cisplatin in patients with renal impairment—this is an absolute contraindication 4

Multidisciplinary Care

Patients with metastatic testicular GCT should be managed at high-volume centers with experienced multidisciplinary teams including medical oncology, urology, and thoracic surgery. 7, 9 The complexity of treatment decisions, surgical expertise required, and long-term survivorship issues necessitate specialized care.