Key Tumor Markers for Testicular Cancer
The three essential tumor markers for testicular cancer are alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), which must be measured before orchiectomy and serially thereafter for diagnosis, risk stratification, and monitoring. 1, 2
Primary Tumor Markers
Alpha-Fetoprotein (AFP)
- AFP is the definitive marker to distinguish nonseminoma from seminoma - pure seminoma NEVER produces AFP 3, 1
- Elevated in approximately 67% of embryonal carcinomas with or without teratoma 4, 5
- Any AFP elevation above normal indicates nonseminomatous elements, even if histology shows "pure seminoma" - these patients must be managed as nonseminoma 1, 3
- Half-life is 5-7 days, allowing reliable monitoring of treatment response 1, 3
- Always elevated in tumors containing yolk-sac elements 4, 5
Beta-Human Chorionic Gonadotropin (β-hCG)
- Elevated in 65% of embryonal carcinomas, 100% of pure choriocarcinomas, and 7.7-30% of seminomas 4, 6
- Cannot distinguish between seminoma and nonseminoma since both tumor types can produce it 3, 7
- Half-life is 24-36 hours (1-3 days), requiring more frequent monitoring 1, 2
- Levels up to 200 IU/L are consistent with pure seminoma, but markedly elevated levels (>100-200 IU/L) suggest choriocarcinoma elements 6, 8
- False positives occur with marijuana use, hypogonadism, and heterophilic antibodies - interpret cautiously 2, 7
Lactate Dehydrogenase (LDH)
- Elevated in approximately 62% of advanced nonseminomatous tumors 5
- Nonspecific marker that can be elevated in both seminoma and nonseminoma 3, 1
- Serves primarily as a prognostic marker rather than diagnostic discriminator 3
- May be the only elevated marker in 3 of 6 patients with otherwise normal AFP and hCG 5
Clinical Application Algorithm
Timing of Marker Measurement
- Obtain all three markers BEFORE any treatment, including orchiectomy - this establishes critical baseline values 1, 2, 1
- Repeat markers minimum 7 days after orchiectomy to determine half-life kinetics and assess for residual disease 1, 2
- Continue monitoring until normalization, even if initially normal post-surgery 1
Diagnostic Interpretation
- At least one marker elevated in approximately 90-91% of patients with clinically demonstrable nonseminomatous disease 4, 5
- Normal markers do NOT exclude testicular cancer - sensitivity is limited, especially in seminoma 1, 2
- Persistent or rising markers after orchiectomy indicate metastatic disease requiring systemic therapy 1, 2
Histology-Marker Correlation
- AFP elevated + any histology = treat as nonseminoma 1, 3, 8
- hCG elevated + AFP normal = consistent with either seminoma or nonseminoma - requires histologic confirmation 3
- Histologic diagnosis of seminoma with elevated AFP = misdiagnosis - there are nonseminomatous elements present 8
- Histologic diagnosis of seminoma with hCG >100-200 IU/L = likely choriocarcinoma elements 6, 8
Risk Stratification and Prognosis
- Post-orchiectomy marker levels are essential for International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic classification 1, 2
- The magnitude of marker elevations directly influences risk classification and treatment intensity 2
- Serial measurements determine appropriate decay rates: AFP should halve every 5-7 days, hCG every 24-36 hours 1, 2
Critical Pitfalls to Avoid
- Failing to obtain pre-orchiectomy markers makes baseline establishment and post-surgical interpretation difficult 2
- Not waiting minimum 7 days post-orchiectomy before repeat testing prevents accurate half-life determination 1, 2
- Treating elevated AFP as seminoma based solely on histology - AFP elevation mandates nonseminoma management regardless of pathology 1, 3
- Over-interpreting mildly elevated hCG without considering false positive causes (marijuana, hypogonadism) 2, 7
- Assuming normal markers exclude cancer - markers have limited sensitivity, particularly in early-stage seminoma 1, 2