What is the work-up for metastatic testicular germ cell tumor?

Work-up of Metastatic Testicular Germ Cell Tumor

For metastatic testicular germ cell tumors, obtain serum tumor markers (AFP, β-HCG, LDH) before any intervention, perform CT imaging of chest/abdomen/pelvis, complete baseline laboratory assessment, and establish IGCCCG prognostic classification to guide treatment intensity. 1, 2

Mandatory Serum Tumor Markers

• AFP (alpha-fetoprotein), β-HCG (beta-human chorionic gonadotropin), and LDH (lactate dehydrogenase) must be obtained before orchiectomy as these are essential for diagnosis, staging, and establishing the IGCCCG prognostic classification that directly determines chemotherapy intensity 1, 2
• LDH is particularly critical in metastatic disease as it serves as an important prognostic factor in the IGCCCG classification system 1
• Post-orchiectomy markers should be repeated at 7 days to assess half-life kinetics: AFP half-life should be <7 days and β-HCG half-life should be <3 days 2
• Delayed decline or rising marker levels indicate residual disease and affect staging 2

Critical pitfall: Normal tumor markers do not exclude metastatic disease—only 40-50% of relapses are associated with marker elevation, with the remainder diagnosed by imaging 3. Never delay obtaining baseline markers before orchiectomy as these values are irreplaceable for monitoring treatment response 2.

Mandatory Imaging Studies

• CT scan of chest, abdomen, and pelvis is required for all patients with metastatic disease to define extent of disease and nodal involvement 1, 2
• Chest X-ray is part of standard staging workup 1
• Brain imaging (MRI preferred, or CT) is mandatory if β-HCG >10,000 IU/L or if >10 lung metastases are present, as these indicate high risk for CNS involvement 1
• Bone scan should be performed if alkaline phosphatase is elevated or if bone-related symptoms are present 1

Baseline Laboratory Assessment

• Complete blood count, renal function (urea, creatinine, electrolytes), and liver function tests are required before initiating treatment 1, 2
• These baseline values are essential for chemotherapy dosing and monitoring treatment toxicity 1

IGCCCG Prognostic Classification

Establishing the IGCCCG prognostic group is mandatory as it directly determines chemotherapy intensity 1:

For Seminoma:

• Good prognosis: Normal AFP, any HCG, any LDH, no nonpulmonary visceral metastases 1
• Intermediate prognosis: Normal AFP, any HCG, any LDH, with nonpulmonary visceral metastases present 1

For Non-Seminomatous Germ Cell Tumors:

• Risk stratification is more complex and includes marker levels, primary tumor site, and presence of nonpulmonary visceral metastases 1
• Good prognosis patients receive BEP × 3 cycles, while intermediate or poor prognosis patients receive BEP × 4 cycles 4

Optional but Recommended Assessments

• Fertility evaluation (total testosterone, LH, FSH, semen analysis) should be considered, with sperm cryopreservation offered before chemotherapy or radiotherapy 1, 4
• Contralateral testis biopsy is recommended in patients with testicular atrophy (<12-16 ml volume) and young age (<30 years) to detect carcinoma in situ 1
• For seminoma specifically, optional markers include hPLAP (placental alkaline phosphatase) and NSE (neurone-specific enolase), though PLAP is only reliable in non-smokers 1

Histological Confirmation

• Diagnosis should be based on histology from radical inguinal orchiectomy whenever possible 1
• In life-threatening metastatic disease with unequivocally elevated AFP or HCG, chemotherapy may be initiated based on clinical picture and markers alone, with orchiectomy postponed until after chemotherapy completion 1
• For retroperitoneal or mediastinal primary presentations, trucut biopsy or mediastinoscopy is needed for tissue diagnosis 1

Critical pitfall: Approximately one-third of patients presenting with retroperitoneal or mediastinal masses will have intratubular germ cell neoplasia in the testis, another third will have "burned out" testicular tumors (scar tissue), and only one-third have true primary extragonadal tumors 1. Therefore, testicular ultrasound is mandatory even when the primary presentation appears extragonadal 1.

Risk Factor Assessment

Document the following risk factors in the clinical history 1, 2:

• Cryptorchidism (relative risk 3.18) 2
• Family history of testicular cancer in first-degree relatives 1
• Testicular atrophy (<12-16 ml volume) 2
• Contralateral testicular tumor 1
• Infertility 2