When to repeat Alpha-Fetoprotein (AFP), Lactate Dehydrogenase (LDH), and Human Chorionic Gonadotropin (HCG) tests after radical orchidectomy?

Timing of Tumor Marker Measurement After Radical Orchiectomy

Serum tumor markers (AFP, hCG, and LDH) should be measured at appropriate half-life intervals after orchiectomy—specifically, AFP should be checked at 5-7 days post-operatively and hCG at 24-36 hours post-operatively to establish nadir levels for accurate staging and risk stratification. 1

Understanding Marker Half-Lives

The timing of post-orchiectomy marker measurement is dictated by the biological half-lives of each marker:

• hCG half-life: 24-36 hours 1
• AFP half-life: 5-7 days 1
• LDH half-life: approximately 1 day 2

Serial measurements may be necessary to confirm whether levels are declining appropriately according to these half-lives or whether they are rising or plateauing, which would indicate residual disease. 1

Immediate Post-Orchiectomy Protocol

Measure AFP, hCG, and LDH shortly after orchiectomy and before any subsequent treatment to establish baseline nadir levels that will guide all future management decisions. 1 The magnitude of these post-orchiectomy elevations directly influences risk stratification according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification and determines whether patients require surveillance, chemotherapy, or other interventions. 1

Critical Timing Considerations:

• For hCG: Recheck at 3-5 days post-orchiectomy (allowing 2-3 half-lives) to confirm normalization or establish declining trend 1, 3
• For AFP: Recheck at 2-3 weeks post-orchiectomy (allowing 2-3 half-lives) to confirm normalization or establish declining trend 1, 4
• For LDH: Recheck at 3-5 days post-orchiectomy 2, 5

When Markers Remain Elevated

If markers remain elevated or are rising after appropriate half-life intervals, this indicates metastatic disease requiring systemic therapy. 1 Do not wait indefinitely for marker normalization when persistent elevation clearly indicates metastatic disease. 6

Borderline Elevations (Within 3× Upper Limit of Normal):

Confirm a rising trend before making treatment decisions, as false-positive elevations can occur. 1 This requires serial measurements over 1-2 weeks to establish trajectory. 1

Clearly Elevated Markers:

• Obtain staging CT chest, abdomen, and pelvis immediately 1, 7
• Classify according to IGCCCG risk categories based on nadir marker levels 1, 6
• Initiate appropriate chemotherapy without further delay 6

Common Pitfalls to Avoid

Do not check markers too early post-orchiectomy (e.g., immediately or within 24 hours), as this does not allow sufficient time for marker decline and may lead to misinterpretation of persistent disease when markers are simply still declining normally. 1

Do not assume a single normal post-operative value is sufficient—serial measurements are often needed to establish whether markers are truly normalizing or simply in the process of declining from very high pre-operative levels. 1

Be aware of false-positive causes:

• AFP: Liver disease, hepatitis, hereditary disorders 4
• hCG: Hypogonadism (cross-reaction with LH), marijuana use, heterophilic antibodies 1
• LDH: Hemolysis, liver disease, myocardial infarction, strenuous exercise, infections 1, 8

Surveillance Schedule After Marker Normalization

Once markers normalize post-orchiectomy, the surveillance schedule depends on stage and treatment:

For Stage I patients on surveillance (no adjuvant therapy):

• Tumor markers every 1-2 months in year 1 1
• Every 2 months in year 2 1, 7
• Every 2-4 months in year 2 (alternative schedule) 1
• Every 3-6 months in years 3-4 1
• Every 6 months in year 5 1
• Annually thereafter 1

For patients who received adjuvant chemotherapy:

• Tumor markers every 3 months during year 2 7
• Less frequent monitoring compared to surveillance-only patients 7