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Risk-adapted management of stage I seminoma: the second Spanish Germ Cell Cancer Group (GG) study

Reviewer: Maria Luisa Veronese, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 7 de junio del 2004

* This presentation discusses off-label use of carboplatin in the treatment of seminoma.

Background

Seminoma represents 45% of all germ cell tumors and 70%-80% of patients present with Stage I disease.  Management of patients with Stage I seminoma after orchiectomy includes surveilance, radiation therapy or chemotherapy.  Surveilance carries high stress, costs, and risk of late relapse (up to 10 years).  Radiation therapy is associated with late toxicity including an increased risk of second tumors and 80% of patients are overtreated.  A previous GG clinical trial has shown that adjuvant carboplatin may be restricted to patients with risk criteria (RC). RC shown to be important prognostic factors for relapse are tumor size >4 cm and invasion to the rete testis. The purpose of this study was to confirm the efficacy of this risk-adapted process using the new International criteria. 

Materials and Methods

• 300 patients with Stage I seminoma (median age 32 years, range 19-66) were enrolled from 42 Institutions betwee 1/1999 and 12/2003
• Patients underwent orchiectomy
• 96 patients (32%) with no RC (tumor size <4 cm and no invasion to rete testes) were managed with surveillance
• 125 (42%) had tumors > 4 cm, 31 (10%) had rete testis involvement, and 48 (16%) had both RC and received single agent adjuvant carboplatin (AUC 7x2 cycles with a 21-day interval)

Results

• Chemotherapy was generally well tolerated: grade 3-4 toxicities were reported in 8.2% of patients; grade 1-2 in 56.5% of patients; and 35% of patients did not experiece any toxicity.
• Most common toxicities were myelotoxicity and asthenia
• Median follow-up was 25 months; 81% of patients had >1 year follow-up
• Relapses were observed in 3% of all patients (4.2% of patients on surveilance and 2.4% of the carboplatin group). 0.8% of tumors > 4 cm, 3.2% of tumor invading rete testis, and 6.3% of tumors with both RC
• Median time to relapse was 8.1 months (range 4-19 months)
• All relapses were at the retroperitoneum (median size was 18 mm, range 11-35)
• All these patients were rendered disease-free with chemotherapy (etoposide + cisplatin)

Author's Conclusions

• Carboplatin is effective in reducing the risk of relapse in patients with high risk stage I seminoma however, the follow-up is short
• The chemotherapy used in this study is well tolerated
• A risk-adapted process is feasible in a large study

Clinical/Scientific Implications

This study investigated the efficacy of a risk-adapted process using the new International criteria in the management of patients with stage I seminoma.  The results indicated that 2 cycles of single agent carboplatin are effective in reducing the relapse rate in high risk stage I seminoma,  However, the follow-up is still very short and there are no data regarding late toxicity using carboplatin in this patient population. Indeed, relapses occur within 2 years in 68.6% of patients and within 3 years in 93.4%. Of concern is the fact that all relapses occurred within the retroperitoneum suggesting that radiotherapy may be superior and should still be considered a first line approach for these patients. 

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