Seminoma Testicular Cancer Treatment Protocols

The risk classification for advanced seminoma testicular cancer is presented below, followed by the treatment protocols for seminoma testicular cancer, including treatment by clinical stages and treatment recommendations for second-line therapy and for persistent or recurrent disease. ^{[1, 2]}

Risk classification for advanced seminoma testicular cancer

The International Germ Cell Cancer Consensus Group (IGCCCG) developed a classification system based on identifying clinically independent prognostic features, including extent of disease and levels of serum tumor markers. In testicular cancer post-orchiectomy, markers are used to determine risk classification. ^[3]

Good-risk seminoma:

• Any primary site
• No nonpulmonary visceral metastases

Intermediate-risk seminoma:

• Any primary site
• Nonpulmonary visceral metastases

Poor-risk seminoma:

• No patients are classified as poor risk

Treatment recommendations for stage I seminoma testicular cancer

Stages IA and IB:

• Radical inguinal orchiectomy is considered the primary treatment for most patients who present with a suspicious testicular mass; pathologic diagnosis may show pure seminoma or nonseminoma germ cell tumors.

• Post-orchiectomy primary treatment for pure seminoma includes surveillance, radiotherapy, 0r chemotherapy. ^[4]

• Surveillance (clinical assessment and imaging studies for at least 5 years) is widely recommended as an option in early-stage seminoma ^{[5, 6, 7]} : American Association of Urology guidelines list surveillance as the preferred option for stage IA disease and as an option for stage IB disease, ^[7] ; National Comprehensive Cancer Network guidelines strongly prefer surveillance for stage IA or IB pT1-3 tumors. ^[5]

• Radical inguinal orchiectomy followed by adjuvant radiation therapy; adjuvant radiation at 20-25 Gy to the infradiaphragmatic area, including the para-aortic and ipsilateral ilioinguinal nodes ^{[8, 9]}

• Radical inguinal orchiectomy followed by adjuvant chemotherapy with carboplatin area under the curve (AUC) 7 for one or two cycles; single-dose carboplatin is less toxic and just as effective as adjuvant radiotherapy after orchiectomy ^{[10, 11]}

Stage IS:

• Generally, treatment for stage IS involves radiation therapy with radiation to the infradiaphragmatic area, including the para-aortic lymph nodes with or without radiation to the ipsilateral ilioinguinal nodes

• Radiation therapy can be given at a dose of 20 Gy (preferred) or 25 Gy ^[5]

Treatment recommendations for stage II seminoma testicular cancer

Stages IIA and IIB:

• Primary treatment includes radiation therapy to the infradiaphragmatic area, including the para-aortic lymph nodes, with radiation to the ipsilateral iliac area; accepted radiation dose is 30-35 Gy

• Chemotherapy may be used for patients with stage IIB; consider four cycles of etoposide and cisplatin (EP) or three cycles of bleomycin, etoposide, and cisplatin (BEP) as alternatives to radiotherapy

Chemotherapy treatment recommendations for stage IIB disease:

• EP regimen for four cycles: Etoposide 100 mg/m² IV on days 1-5 plus  cisplatin 20 mg/m² IV on days 1-5; every 21d ^{[12, 13]} or

• BEP regimen for three cycles: Etoposide 100 mg/m² IV on days 1-5 plus  cisplatin 20 mg/m² IV on days 1-5 plus  bleomycin 30 U IV weekly on days 1, 8, and 15; every 21d ^{[14, 5]}

Stages IIC and III:

Patients with stage II or III seminoma are considered to have good risk, with the exception of patients who have stage III disease with nonpulmonary visceral metastases, who are classified as intermediate-risk patients.

Good-risk seminoma: Primary chemotherapy: 

• EP regimen for four cycles: Etoposide 100 mg/m² IV on days 1-5 plus  cisplatin 20 mg/m² IV on days 1-5; every 21d ^{[12, 13]} or

• BEP regimen for three cycles: Etoposide 100 mg/m² IV on days 1-5 plus  cisplatin 20 mg/m² IV on days 1-5 plus  bleomycin 30 U IV weekly on days 1, 8, and 15; every 21d ^{[14, 5]}

Intermediate-risk seminoma: Primary chemotherapy: 

• BEP regimen for four cycles: Etoposide 100 mg/m² IV on days 1-5 plus  cisplatin 20 mg/m² IV on days 1-5 plus  bleomycin 30 U IV weekly on days 1, 8, and 15; every 21d ^{[14, 5]}

• VIP for four cycles is another option, but BEP is preferred. 

Second-line treatment recommendations

VeIP (vinblastine, ifosfamide, and cisplatin) regimen ^[15] :

• Vinblastine 0.11 mg/kg IV push on days 1-2 plus  ifosfamide 1200 mg/m² IV daily on days 1-5 plus mesna 400 mg/m² IV infused over 30 min before ifosfamide, then 4h and 8h after the start of ifosfamide on days 1-5 plus  cisplatin (CDDP) 20 mg/m² IV on days 1-5; every 21d for 4 cycles

TIP (paclitaxel, ifosfamide, and cisplatin) regimen ^{[16, 17]} :

• Paclitaxel 250 mg/m² IV on day 1 plus  ifosfamide 1500 mg/m² IV on days 2-5 plus  cisplatin (CDDP) 25 mg/m² IV on days 2-5 plus  mesna 500 mg/m² IV infused over 30 min before ifosfamide, then at 4h and 8h after each dose of ifosfamide on days 2-5; every 21d for 4 cycles

VIP (etoposide, ifosfamide, and cisplatin) regimen ^{[18, 19]} :

• Etoposide (VP-16) 75 mg/m² IV infused over 1h on days 1-5 plus  ifosfamide 1200 mg/m² IV infused over 3h on days 1-5 plus  cisplatin (CDDP) 20 mg/m² IV infused over 1h on days 1-5 plus  mesna 400 mg/m² IV over 30 min before ifosfamide and then 4h and 8h after the start of each ifosfamide dose on days 1-5; every 21d

Persistent or recurrent disease treatment recommendations

Patients who have persistent or recurrent disease should be given palliative chemotherapy that includes gemcitabine and oxaliplatin.

GEMOX (gemcitabine plus oxaliplatin) regimen ^{[20, 21]} :

• Gemcitabine 1000-1250 mg/m² IV infused over 30 min on days 1 and 8 followed by  oxaliplatin 130 mg/m² IV infused over 2h on day 1; every 21d