What is the next step if Human Chorionic Gonadotropin (HCG) and Alpha-Fetoprotein (AFP) levels remain elevated after orchiectomy?

Management of Elevated HCG and AFP After Orchiectomy

For patients with persistently elevated HCG and AFP after orchiectomy, chemotherapy should be initiated rather than waiting for repeat testing, as these markers indicate the presence of metastatic disease requiring systemic treatment. 1

Understanding Tumor Marker Significance

• Serum tumor markers (STMs) including AFP and hCG are essential for diagnosis, staging, prognosis, and treatment planning in testicular cancer 2
• The half-life for hCG is 24-36 hours and 5-7 days for AFP; persistent elevation beyond these expected decay rates indicates residual disease 1
• Elevated markers post-orchiectomy without visible radiological metastases (stage IS) indicate the need for systemic treatment 1

Evaluation Algorithm

1. Confirm true elevation:

   • Rule out false positives (marijuana use, hypogonadism for hCG; liver disease for AFP) 2
   • For borderline elevations (within 3x upper limit of normal), confirm a rising trend before making management decisions 1

2. Staging workup:

   • Obtain CT scan of chest, abdomen, and pelvis with IV contrast to evaluate for metastatic disease 1
   • In the presence of elevated markers, a CT chest is strongly recommended over chest X-ray 1

3. Risk stratification:

   • Classify according to International Germ Cell Cancer Collaborative Group (IGCCCG) risk categories based on marker levels 1
   • AFP >1,000 μg/L and hCG >5,000 U/L indicate at least intermediate risk disease 1

Treatment Decision

• Persistently elevated AFP: Patients with elevated AFP after orchiectomy have a very high risk of relapse (83%) and should receive immediate chemotherapy rather than repeat testing 3
• Persistently elevated hCG: Although the relapse risk is lower (25%), systemic chemotherapy is still indicated rather than observation 3
• Both markers elevated: This represents metastatic disease requiring immediate chemotherapy based on IGCCCG risk classification 1

Chemotherapy Regimen Selection

• Chemotherapy regimen and number of cycles must be based on IGCCCG risk stratification 1
• Good-risk disease: BEP (bleomycin, etoposide, cisplatin) x3 cycles or EP (etoposide, cisplatin) x4 cycles 1
• Intermediate or poor-risk disease: BEP x4 cycles 1

Common Pitfalls

• Waiting too long for marker normalization when persistent elevation clearly indicates metastatic disease 1, 2
• Not obtaining adequate imaging studies (CT chest, abdomen, pelvis) before initiating treatment 1
• Failing to classify patients according to IGCCCG risk categories, which determines the appropriate chemotherapy regimen 1
• Not considering rare causes of persistent marker elevation such as Hereditary Persistence of AFP (HPAFP) in patients with otherwise negative workup 4