What tumor markers are used to diagnose testicular cancer?

Testicular Tumor Markers

The three essential tumor markers for diagnosing testicular cancer are alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), which should be measured in all patients with suspected testicular cancer before orchiectomy. 1

Primary Tumor Markers and Their Significance

Essential Markers

• Alpha-fetoprotein (AFP)

  • Produced by nonseminomatous cells (embryonal carcinoma, yolk-sac tumor)
  • Half-life: 5-7 days
  • Never elevated in pure seminoma (if elevated in a patient with histologically "pure" seminoma, an undetected focus of nonseminoma should be suspected) 1
  • Elevated in 60-67% of nonseminomas 2, 3

• Beta-human chorionic gonadotropin (β-hCG)

  • Can be elevated in both seminoma and nonseminoma
  • Half-life: 1-3 days
  • Elevated in 28% of pure seminomas and 53% of nonseminomas 3
  • Always elevated in choriocarcinoma 2

• Lactate dehydrogenase (LDH)

  • Less specific than AFP and β-hCG but important for prognostic stratification
  • Elevated in approximately 29% of seminomas and 39% of nonseminomas 3
  • May remain elevated in 30-34% of patients after treatment 3

Clinical Utility of Tumor Markers

Diagnostic Value

• At least one marker (AFP, β-hCG, or LDH) is elevated in 91% of patients with nonseminomatous germ cell tumors 2
• Overall, serum tumor markers have low sensitivity, especially in seminoma, so normal marker levels do not exclude germ cell tumors 1
• LDH has lower specificity as it may be elevated due to various reasons 1

Timing of Marker Measurements

1. Before orchiectomy:

   • Essential for baseline values and supporting diagnosis 1
   • Helps distinguish between seminoma and nonseminoma

2. After orchiectomy:

   • Important for prognostic stratification 1
   • Should be followed in patients with initially elevated markers until normalization
   • Persistent or increasing markers after orchiectomy usually indicate metastatic disease 1

3. During treatment and follow-up:

   • Should be measured at the start of each chemotherapy cycle for nonseminoma 1
   • Periodically monitored to detect relapse in nonseminoma and advanced seminoma 1
   • Not recommended for detecting relapse in patients treated for stage I seminoma 1

Special Considerations

Marker Patterns and Histology

• AFP is always elevated in tumors containing yolk-sac elements 2
• β-hCG is always elevated in choriocarcinoma 2
• However, absence of these histologic types does not preclude elevations of the respective markers 2

Relapse Monitoring

• In relapsing patients, marker patterns may change compared to initial presentation 3
• Sustained or rising levels of AFP or β-hCG always indicate persistent or recurrent tumor 2

Optional Additional Markers

• For seminoma only: human placental alkaline phosphatase (hPLAP) and neuron-specific enolase (NSE) may provide additional information but are not mandatory 1
• PLAP is reliable only in non-smokers as smoking interferes with measurement 1

Pitfalls and Caveats

1. False negatives: Normal marker levels do not exclude testicular cancer, particularly in seminoma where marker sensitivity is low 1

2. Marker half-life: Failure of AFP (half-life 5-7 days) or β-hCG (half-life 1-3 days) to decline according to their half-lives suggests residual disease 1

3. Seminoma with elevated AFP: Pure seminoma does not produce AFP; any elevation indicates the presence of nonseminomatous elements, even if not detected histologically 1

4. LDH limitations: Less specific than other markers and may remain elevated after treatment for reasons unrelated to cancer 1, 3

5. Marker changes in relapse: Thirteen out of 27 relapsing patients in one study showed different marker patterns compared to initial presentation 3

In conclusion, while AFP, β-hCG, and LDH are the cornerstone tumor markers for testicular cancer diagnosis and management, their interpretation must be done in conjunction with clinical findings, imaging, and histopathology for optimal patient outcomes.