What are the diagnostic markers and treatment options for testicular cancer?

Testicular Cancer Markers

The mandatory serum tumor markers for testicular cancer are alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), and lactate dehydrogenase (LDH), which must be obtained before orchiectomy and repeated post-operatively to guide staging, risk stratification, and treatment decisions. 1, 2

Mandatory Diagnostic Markers

Pre-Orchiectomy Assessment

• AFP and β-HCG are essential for all testicular germ cell tumors (both seminoma and non-seminoma), as they provide diagnostic confirmation and establish baseline values for subsequent monitoring 1, 2
• LDH must be measured in addition to AFP and β-HCG in advanced disease, as it serves as a critical prognostic factor in the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system 1, 2
• These markers should be drawn immediately when testicular cancer is suspected, even before surgical intervention 1, 3, 2

Post-Orchiectomy Monitoring

• Nadir markers must be repeated at appropriate half-life intervals after orchiectomy: AFP should be checked at 5-7 days (half-life 5-7 days) and β-HCG at 24-36 hours to 3 days (half-life 24-36 hours) 1, 2
• Markers must be followed until complete normalization, as delayed decline or rising levels indicate residual disease and affect staging 1, 2
• Failure of markers to normalize at expected intervals suggests persistent metastatic disease requiring immediate staging workup 2

Optional but Informative Markers

Seminoma-Specific Markers

• Placental alkaline phosphatase (PLAP) and neurone-specific enolase (NSE) can provide additional information for treatment monitoring and follow-up in advanced seminoma, but are not mandatory 1
• PLAP is only reliable in non-smokers, as smoking interferes with accurate measurement 1

Critical Diagnostic Principles

Marker-Histology Correlation

• Pure seminoma never secretes AFP—if AFP is elevated with a histologic diagnosis of seminoma, there is an element of non-seminomatous components (typically embryonal carcinoma) and the patient must be treated as having non-seminoma 3, 4
• Highly elevated β-HCG (>100 ng/mL or >5000 IU/L) in seminoma usually indicates an element of choriocarcinoma 4
• Elevated AFP with histologic choriocarcinoma indicates an embryonal carcinoma component 4

Prognostic Risk Stratification

The IGCCCG classification uses marker levels to determine treatment intensity 1, 2:

Good Prognosis Non-Seminoma:

• AFP <1000 ng/mL AND
• β-HCG <5000 IU/L AND
• LDH <1.5× upper limit of normal
• 5-year survival: 92% 1

Intermediate Prognosis Non-Seminoma:

• AFP 1000-10,000 ng/mL OR
• β-HCG 5000-50,000 IU/L OR
• LDH 1.5-10× upper limit of normal
• 5-year survival: 80% 1

Poor Prognosis Non-Seminoma:

• AFP >10,000 ng/mL OR
• β-HCG >50,000 IU/L OR
• LDH >10× upper limit of normal OR
• Mediastinal primary OR
• Non-pulmonary visceral metastases
• 5-year survival: 48% 1

Seminoma Classification:

• Good prognosis: Normal AFP, any β-HCG, any LDH, no non-pulmonary visceral metastases (90% of cases, 86% 5-year survival) 1, 2
• Intermediate prognosis: Normal AFP, any β-HCG, any LDH, with non-pulmonary visceral metastases (10% of cases, 72% 5-year survival) 1, 2
• No seminoma patients are classified as poor prognosis 1

Essential Imaging for Staging

Primary Evaluation

• Scrotal ultrasound with Doppler (7.5 MHz transducer minimum) is mandatory for any suspected testicular mass, with nearly 100% sensitivity for detecting intrascrotal masses 1, 3
• MRI should NOT be used as initial evaluation for testicular lesions suspicious for neoplasm 1

Metastatic Workup

• CT scan of chest, abdomen, and pelvis is required for all patients with confirmed testicular cancer to assess for metastatic disease 1, 2
• Brain MRI is mandatory if β-HCG >10,000 IU/L or >10 lung metastases are present, as these indicate high risk for CNS involvement 2
• Bone scan only if alkaline phosphatase is elevated or bone symptoms present 1, 2

Treatment Implications Based on Markers

Stage I Disease with Elevated Markers

• Pathologic stage I non-seminoma with persistently elevated markers after orchiectomy is actually stage II or III disease, requiring systemic therapy rather than surveillance 4
• This represents occult metastatic disease not detected on imaging 4

Chemotherapy Selection

• Good-risk disease: BEP (bleomycin, etoposide, cisplatin) ×3 cycles or EP (etoposide, cisplatin) ×4 cycles 3
• Intermediate or poor-risk disease: BEP ×4 cycles 3
• Marker normalization after chemotherapy indicates effective therapeutic response, though residual masses still require evaluation 4

Critical Pitfalls to Avoid

• Never delay obtaining tumor markers before orchiectomy—this information is essential for accurate staging and cannot be reliably obtained afterward 3, 2
• Never dismiss normal markers in the presence of a solid testicular mass—up to 30% of non-seminomas may have normal markers at presentation 5
• Never treat based on histology alone if markers contradict the pathology—markers take precedence in determining treatment approach 3, 4
• Never assume marker normalization means no residual disease—21-30% of patients with normalized markers after chemotherapy still have residual teratoma or viable carcinoma requiring surgical resection 4

Fertility and Hormonal Assessment

• Total testosterone, LH, FSH, and semen analysis should be obtained before treatment, particularly in patients considering fertility preservation 1, 2
• Sperm banking must be offered before orchiectomy in post-pubertal patients, especially those without a normal contralateral testis or with known subfertility 1, 3, 2