What labs are used to monitor testicular cancer?

Laboratory Monitoring for Testicular Cancer

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

Core Tumor Markers (Mandatory)

Alpha-Fetoprotein (AFP)

• Half-life: 5-7 days 1
• Produced by nonseminomatous germ cell tumors, specifically embryonal carcinoma and yolk sac tumor 1
• Elevated AFP definitively excludes pure seminoma and indicates nonseminomatous components even if histology appears pure seminoma 1
• Elevated in approximately 47% of patients with metastatic testicular cancer at diagnosis 2

Beta-Human Chorionic Gonadotropin (β-HCG)

• Half-life: 1-3 days 1
• Elevated in approximately 60% of patients with metastatic disease 2
• Can be mildly elevated in approximately 20% of seminoma patients due to syncytiotrophoblastic giant cells 1
• Quantitative analysis of the beta subunit is required 1

Lactate Dehydrogenase (LDH)

• Less specific marker than AFP and β-HCG, but critical for prognostic stratification 1
• Elevated in approximately 64% of patients with metastatic disease 2
• Essential for International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification 1
• Can be elevated by numerous non-malignant conditions including strenuous exercise, liver disease, myocardial infarction, hemolysis, and pneumonia 1

Timing of Marker Assessment

Pre-Orchiectomy

• Obtain AFP, β-HCG, and LDH before any surgical intervention to establish baseline values for diagnosis and subsequent monitoring 1, 3
• Normal marker levels do not exclude testicular cancer, as markers have low sensitivity especially in seminoma 1

Post-Orchiectomy

• Repeat markers approximately 7 days after orchiectomy to assess half-life kinetics 3
• Follow markers serially until normalization or until they reach a stable plateau 1
• Persistent or rising markers after orchiectomy indicate metastatic disease 1
• Delayed decline beyond expected half-life suggests residual disease and affects staging 3

During Active Treatment

• Measure markers on day 1 of each chemotherapy cycle before the next treatment begins 4
• Transient marker elevation during the first week of chemotherapy may occur due to tumor lysis and does not indicate progression 1
• If markers rise between day 1 of cycle 1 and day 1 of cycle 2, repeat midway through cycle 2 to determine if decline has begun 1

Surveillance Schedules by Clinical Stage

Stage I Disease (Surveillance Only, No Adjuvant Therapy)

• Year 1: AFP, β-HCG, and LDH every 2 months 5
• Year 2: AFP, β-HCG, and LDH every 2 months 5
• Years 3-5: AFP, β-HCG, and LDH every 3-4 months 5
• Beyond 5 years: Annual markers may be considered 5

Stage I Disease (After Adjuvant Chemotherapy)

• Year 1-2: AFP, β-HCG, and LDH every 3 months 5
• Imaging only as clinically indicated, not routine 5

Advanced Disease (Post-Chemotherapy)

• Markers should be obtained before each follow-up visit 1
• Approximately 40-50% of relapses in stage I disease and 30% after chemotherapy are detected by marker elevation alone without imaging findings 4

Critical Interpretation Pitfalls

False Elevations of β-HCG

• Hypogonadism from orchiectomy and chemotherapy can cause low testosterone, leading to increased pituitary production of LH and hCG that cross-reacts with some assays 1
• Supplemental testosterone administration reduces this false elevation by suppressing gonadotropin-releasing hormone 1
• Heterophilic antibodies can cause false-positive hCG results 1

False Elevations of AFP

• Hepatocellular carcinoma and other non-germ cell malignancies can produce AFP 1
• Liver disease can elevate AFP independent of malignancy 1

LDH Specificity Issues

• LDH elevation alone without AFP or β-HCG elevation requires careful clinical correlation due to numerous non-malignant causes 1
• LDH has proven utility primarily for prognosis in chemotherapy-naïve patients with metastatic disease 1

Optional Markers (Not Routinely Recommended)

Placental Alkaline Phosphatase (PLAP)

• May provide additional information for advanced seminoma monitoring 1
• Only reliable in non-smokers, as smoking causes false-positive elevations in approximately 20% of cases 1, 6
• Not recommended for routine use 1, 4

Neuron-Specific Enolase (NSE)

• Optional for seminoma only 1
• Not recommended for routine clinical use 4

Risk Stratification Using Markers

IGCCCG Classification (Serum Marker Thresholds)

• S1 (Good prognosis): LDH <1.5× upper limit of normal (ULN), β-HCG <5,000 IU/L, AFP <1,000 ng/mL 1
• S2 (Intermediate prognosis): LDH 1.5-10× ULN, β-HCG 5,000-50,000 IU/L, AFP 1,000-10,000 ng/mL 1
• S3 (Poor prognosis): LDH >10× ULN, β-HCG >50,000 IU/L, or AFP >10,000 ng/mL 1

When Markers Indicate Recurrence

Immediate Actions Required

• Confirm elevation by repeating markers to establish a rising trend rather than laboratory variation 5
• Obtain staging CT of chest, abdomen, and pelvis with IV contrast immediately 5
• Urgent referral to medical oncology for treatment consideration 5
• Approximately 10% of relapses present with marker elevation only without radiographic evidence of disease 4

Marker-Only Relapse Management

• Rising markers without imaging evidence of metastatic disease still requires treatment 4
• "Desperation surgery" with rising markers is only indicated if no curative chemotherapy options remain, all residual masses are completely resectable, and no hCG elevation is present 4