Poor-prognosis Germ Cell Tumours: Room for Improvement

Abstract

Patients with poor-prognosis germ cell tumours according to the International Germ Cell Collaborative Group [1] face an overall survival (OS) of only approximately 50%. In three randomized trials of high-dose chemotherapy regimens compared to the standard treatment consisting of four courses of bleomycin, etoposide, and cisplatin (BEP), no superiority of dose intensification in a first-line setting could be shown [2–4]. However, in single-center studies, OS rates of up to 75% were achieved if patients were selected properly and treated in highly specialized units for medical oncology and urological surgery [5,6]. In this issue of European Urology, Huddart et al [7] present data from a randomized phase 2 trial of a doseintensified regimen (two cycles of carboplatin, bleomycin, and vincristin, two cycles of bleomycin and vincristin, and three cycles of BEP; CBOP/BEP) against the standard four courses of BEP in 89 patients. The trial was powered to achieve a favorable response rate (FRR) of 80% as defined by complete remission, partial remission with negative markers, or pathological complete remission with the new regimen. The CBOP/BEP regimen had an FRR of 74%, compared to 61% for BEP. The 2-yr OS rates were 67% and 61% for CBOP/BEP and BEP, respectively. Toxicity was high, with 96% and 63% Common Terminology Criteria grade 3 for CBOP/BEP and BEP, respectively. Five of 32 deaths were related to toxicity. The authors concluded that the 13% difference in FRR justifies an international phase 3 trial. This is critical for several reasons. (1) Patients with poor-prognosis germ cell cancer are rare, and centralized treatment in Europe has not been achieved. This is one of the main reasons why the latest EORTC trial by Daugaard et al [4] had to be stopped prematurely. Thus, it will be very difficult to accrue enough patients to prove a 13% difference in a phase 3 setting.