What lab values indicate testicular cancer?

Lab Values Indicating Testicular Cancer

The three critical serum tumor markers for testicular cancer are alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), and lactate dehydrogenase (LDH), which should be measured before orchiectomy, during treatment, and throughout follow-up. 1

Primary Tumor Markers

Alpha-Fetoprotein (AFP)

• AFP is produced exclusively by nonseminomatous germ cell tumors (embryonal carcinoma and yolk sac tumor) and is never elevated in pure seminoma 1
• Half-life is 5-7 days, which is critical for monitoring treatment response 1
• Any elevation of AFP in a histologically "pure" seminoma indicates an undetected focus of nonseminoma, and the patient must be treated as having nonseminomatous disease 1
• Elevated in approximately 47-67% of patients with metastatic nonseminomatous germ cell tumors 2, 3

Beta-Human Chorionic Gonadotropin (β-HCG)

• May be elevated in both seminomas and nonseminomas, making it less specific than AFP 1
• Half-life is 1-3 days 1
• Elevated in approximately 15-20% of advanced seminomas and 40-64% of advanced nonseminomatous tumors 4, 2, 3
• Levels up to 200 IU/L correlate with pure seminoma; extremely high levels suggest nonseminomatous components or choriocarcinoma 5
• Quantitative analysis of the beta subunit should be performed 1

Lactate Dehydrogenase (LDH)

• LDH is the least specific marker but still clinically important 1
• Elevated in approximately 62-64% of patients with metastatic disease 2, 3
• LDH >2.5 times the upper limit of normal (ULN) in seminoma indicates worse prognosis and changes risk stratification 1
• May be elevated in 31% of cases where AFP and β-HCG are normal, making it valuable for detecting disease when other markers are negative 3

Clinical Interpretation Guidelines

Marker Patterns by Histology

• Pure seminoma: β-HCG may be elevated (up to 30% of cases), LDH may be elevated, but AFP must be negative 1, 5
• Nonseminoma: Any combination of AFP, β-HCG, and LDH may be elevated 1
• Choriocarcinoma: Always shows elevated β-HCG 3
• Yolk sac tumor: Always shows elevated AFP 3

Prognostic Stratification (IGCCCG Classification)

Good prognosis nonseminoma requires all of the following 1:

• AFP <1,000 ng/mL
• β-HCG <5,000 IU/L (1,000 ng/mL)
• LDH <1.5 × ULN
• Testis/retroperitoneal primary
• No non-pulmonary visceral metastases

Intermediate prognosis nonseminoma includes any of 1:

• AFP 1,000-10,000 ng/mL, or
• β-HCG 5,000-50,000 IU/L, or
• LDH 1.5-10 × ULN

Poor prognosis nonseminoma includes any of 1:

• AFP >10,000 ng/mL, or
• β-HCG >50,000 IU/L (10,000 ng/mL), or
• LDH >10 × ULN
• Mediastinal primary tumor
• Non-pulmonary visceral metastases

Timing of Marker Assessment

Pre-orchiectomy: Obtain baseline AFP, β-HCG, and LDH before any therapeutic intervention 1

Post-orchiectomy: Repeat markers to assess for normalization based on half-lives (AFP: 5-7 days; β-HCG: 1-3 days) 1

During treatment: Monitor markers before, during, and after chemotherapy or radiation 1

Surveillance: Measure markers at every follow-up visit, as elevated levels are the earliest sign of relapse 1

Critical Pitfalls to Avoid

False positives for β-HCG can occur due to 4:

• Hypogonadism (low testosterone causing increased LH production)
• Marijuana use
• Heterophilic antibodies (especially in women)

Normal marker levels do not exclude testicular cancer: At least one marker is elevated in only 91% of patients with advanced nonseminomatous disease, meaning 9% have normal markers despite metastatic disease 3

Persistent or rising markers after orchiectomy always indicate metastatic disease and require immediate staging with CT imaging 1, 3

Carcinoembryonic antigen (CEA) is not useful as a tumor marker in testicular cancer and should not be routinely measured 2, 3

Additional Marker Considerations

Human placental alkaline phosphatase (hPLAP) shows the highest sensitivity (51.1%) among individual markers and is elevated most frequently in testicular cancer, though it is not included in standard guidelines 6

The combination of AFP, β-HCG, and LDH provides significantly better diagnostic accuracy than any single marker alone 6

Rapidly increasing β-HCG with symptoms of disseminated disease may justify starting chemotherapy immediately without waiting for biopsy confirmation 1, 4