What is the prognosis and first-line treatment for a patient with stage II seminoma, and what surveillance follow-up schedule is recommended?

Stage II Seminoma: Prognosis and Management

Prognosis

Stage II seminoma has an excellent prognosis with overall survival ≥98% and cause-specific survival of 94-100%, regardless of treatment modality chosen. 1, 2

• 5-year and 10-year relapse-free survival rates are 85-95% across all stage II disease when treated appropriately 2, 3
• Stage IIA patients achieve 91-97% relapse-free survival at 5 years 2, 4
• Stage IIB patients achieve 89-93% relapse-free survival at 5 years 2, 3
• The excellent survival outcomes are maintained because salvage therapy is highly effective for the minority who relapse 2

Prognostic Factors by Lymph Node Size

• Lymph nodes ≤3 cm (stage IIA/IIB): Excellent prognosis with >95% cure rates 1
• Lymph nodes >3 cm but ≤5 cm (stage IIB): Very good prognosis with 89-93% relapse-free survival 2, 5
• Lymph nodes >5 cm (stage IIC): Reduced prognosis with 64-75% relapse-free survival, requiring chemotherapy 5, 3

First-Line Treatment Algorithm

For Stage IIA/IIB with Lymph Nodes ≤3 cm

The standard treatment is para-aortic and ipsilateral iliac radiotherapy to 30 Gy (stage IIA) or 36 Gy (stage IIB) in 2 Gy fractions. 1

• Radiotherapy fields: Upper border at T11, lower border at ipsilateral acetabulum, with lateral extensions modified according to lymph node location 1
• Alternative option: Multi-agent cisplatin-based chemotherapy (3 cycles BEP or 4 cycles EP if bleomycin contraindicated) is equally effective with different toxicity profiles 1
• Chemotherapy may have lower risk of secondary malignancy but more acute toxicities compared to radiotherapy 1
• Emerging option: Primary RPLND may be offered for patients wishing to avoid long-term toxicities of chemotherapy or radiotherapy, though data remain limited 1

For Stage IIB with Lymph Nodes >3 cm

Chemotherapy is the recommended first-line treatment. 1

• Standard regimen: 3 cycles of BEP (bleomycin, etoposide, cisplatin) using either 3-day or 5-day schedule for good prognosis patients 1
• Alternative if bleomycin contraindicated: 4 cycles of EP (etoposide, cisplatin) 1

For Stage IIC/III (Advanced Disease)

Chemotherapy with PEB is standard treatment: 3 cycles for good prognosis patients, 4 cycles for intermediate prognosis patients 1, 6

• 5-day schedule: Cisplatin 20 mg/m² days 1-5, etoposide 100 mg/m² days 1-5, bleomycin 30 mg absolute bolus days 1,8,15 1
• 3-day schedule (good prognosis only): Cisplatin 50 mg/m² days 1-2, etoposide 165 mg/m² days 1-3, bleomycin 30 mg absolute bolus days 1,8,15 1
• Intermediate prognosis alternative: 4 cycles VIP (etoposide, ifosfamide, cisplatin) with G-CSF if bleomycin contraindicated 1, 6

Post-Treatment Management of Residual Masses

After Chemotherapy

• Complete response: Follow-up only, no additional treatment required 1, 6
• Residual mass <3 cm: Follow-up only, PET scan optional 1
• Residual mass ≥3 cm: PET scan recommended at minimum 6 weeks after chemotherapy completion 1, 6

PET Scan Interpretation

• PET negative: Follow-up only without active treatment 1, 6
• PET positive: Strong evidence for residual active tumor; surgical resection should be considered 1, 6
• No PET performed for lesions >3 cm: Either resection or surveillance until resolution/progression 1

Surveillance Follow-Up Schedule

For Stage IIA/IIB Treated with Radiotherapy

• Physical examination and tumor markers: 4 times in year 1,3 times in year 2 times in years 3-5 1
• CT abdomen/pelvis: 2 times in year 2, then as clinically indicated 1
• Chest X-ray: As clinically indicated 1

For Stage IIC/III Treated with Chemotherapy (Good Prognosis)

• Physical examination and tumor markers: 3 times in years 1-2, then annually in years 3-5 1, 6
• CT abdomen/pelvis: 2 times in year 1, then annually 1
• Chest X-ray: 6 times in year 1,3 times in year 2 times in years 3-5 1

For Stage IIC/III Treated with Chemotherapy (Intermediate Prognosis)

• Physical examination and tumor markers: Every 2 months in year 1, every 3 months in year 2, every 4 months in year 3, every 6 months in years 4-5 6
• CT abdomen/pelvis: As needed until complete response, then according to chest X-ray schedule 6
• Chest X-ray: Every 4 months in year 1, every 6 months in year 2, annually in years 3-5 6

Long-Term Monitoring

• Tumor markers assessed: AFP, HCG, LDH at each visit 1
• Late effects monitoring: Urea and electrolytes, fasting lipids (HDL, LDL), triglycerides, fasting glucose, FSH, LH, testosterone 1
• Cardiovascular risk factor monitoring is essential given elevated risk after chemotherapy or radiotherapy 1

Critical Clinical Pitfalls

Pre-Treatment Verification

• Clinical stage IIA seminoma should be verified beyond standard imaging (e.g., fine-needle biopsy) before initiating systemic chemotherapy 1
• Do not delay treatment: Chemotherapy should be given without delay or dose reduction at 21-day intervals 1

Treatment Selection Errors

• Do not use prophylactic mediastinal irradiation as it does not improve outcomes and increases toxicity 2, 5, 3
• Do not use carboplatin monotherapy for stage II disease as it is inadequate; multi-agent cisplatin-based regimens are required 1
• Stage IIC disease (>5 cm nodes) should not receive primary radiotherapy due to high relapse rates (25-36%); chemotherapy is mandatory 5, 3

Fertility Preservation

• Sperm cryopreservation must be offered before any chemotherapy or radiotherapy as these treatments can cause permanent infertility 1

Secondary Malignancy Risk

• Secondary solid tumors develop in 5.6% of testicular cancer survivors, with risk increasing with younger age at diagnosis 1
• Chemotherapy may carry lower secondary malignancy risk than radiotherapy, particularly for gastrointestinal and hematologic malignancies in the radiation field 1