What are the key lab markers for testis cancer?

Key Lab Markers for Testicular Cancer

The three essential serum 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, after surgery, and throughout follow-up for staging, risk stratification, treatment monitoring, and relapse detection. 1

The Three Core Markers

Alpha-Fetoprotein (AFP)

• AFP is the definitive marker to distinguish nonseminoma from seminoma because pure seminomas never produce AFP 2, 3
• Any elevation of AFP above normal indicates nonseminomatous elements, even when histology appears to show "pure seminoma" 2, 3
• AFP has a half-life of 5-7 days, allowing reliable monitoring of treatment response 1, 3
• Critical clinical rule: If AFP is elevated, treat as nonseminoma regardless of what the pathology report says 2, 3

Beta-Human Chorionic Gonadotropin (β-hCG)

• β-hCG can be elevated in both seminomas (15-20% of advanced cases) and nonseminomas (40% of advanced cases), making it useless for distinguishing between tumor types 4, 2, 3
• β-hCG has a shorter half-life of 1-3 days 1, 3
• Particularly elevated in choriocarcinoma components 4
• Common pitfall: False positives can occur with hypogonadism, marijuana use, or heterophilic antibodies 3

Lactate Dehydrogenase (LDH)

• LDH is the least specific marker but remains clinically important for prognosis 3
• Can be elevated in both seminomas and nonseminomas 1, 2
• Serves primarily as a prognostic marker rather than diagnostic discriminator 2

Risk Stratification Using Markers

The International Germ Cell Cancer Collaborative Group (IGCCCG) classification uses these markers for prognostic stratification: 1

Good Prognosis Nonseminoma Requires:

• AFP <1,000 ng/mL 1, 3
• β-hCG <5,000 IU/L 1, 3
• LDH <1.5 × upper limit of normal (ULN) 1, 3

Marker Stage Classification for Nonseminoma:

• S0: Normal markers 1
• S1: LDH <1.5 × ULN and β-hCG <1,000 IU/L and AFP <1,000 ng/mL 1
• S2: LDH 1.5-10 × ULN or β-hCG 1,000-10,000 IU/L or AFP 1,000-10,000 ng/mL 1
• S3: LDH >10 × ULN or β-hCG >10,000 IU/L or AFP >10,000 ng/mL 1

Timing of Marker Assessment

Pre-Treatment

• Obtain baseline AFP, β-hCG, and LDH before any therapeutic intervention 1, 3
• Markers should be drawn before orchiectomy whenever possible 1

Post-Orchiectomy

• Repeat markers minimum 7 days after orchiectomy to assess normalization based on half-lives 1, 3
• Follow markers until complete normalization or plateau 1
• Critical decision point: Persistent or rising markers after orchiectomy indicate metastatic disease requiring immediate CT staging 3

During Treatment and Follow-Up

• Monitor markers before, during, and after chemotherapy or radiation 3
• Measure at every follow-up visit to detect early relapse 3
• Important caveat: In patients requiring urgent chemotherapy due to life-threatening disease with typical clinical picture and elevated markers, treatment can begin without waiting for biopsy 1

Clinical Application Algorithm

When Evaluating a Testicular Mass:

1. Measure all three markers (AFP, β-hCG, LDH) immediately 1, 3
2. If AFP is elevated → Diagnose and treat as nonseminoma, regardless of histology 2, 3
3. If AFP is normal with elevated β-hCG and/or LDH → Could be either seminoma or nonseminoma; histologic confirmation required 2
4. If all markers are normal → Does not exclude testicular cancer; approximately 40-50% of patients have normal markers 5

Important Limitations and Pitfalls

• Only about 60% of testicular cancer patients have elevated markers at presentation 6, 5
• In pure seminomas, only 30.3% have any marker elevation (primarily β-hCG or LDH) 5
• In nonseminomas, 73.8% have elevated β-hCG or AFP 5
• Marker patterns may change upon relapse, requiring reassessment of all three markers 5
• LDH remains elevated in 30-35% of patients after successful treatment, limiting its utility for surveillance 5