GETUG-12 assessed docetaxel-estramustine in patients with high-risk localized prostate cancer: the primary endpoint of relapse-free survival (RFS) was met (adjusted HR: 0.71 [95% CI: 0.54-0.94], p = 0.017) (Lancet Oncol 2015; 16: 787-94). This analysis updates RFS and assesses clinical events for the first time.
Eligibility included non-pretreated high-risk localized prostate cancer, defined as ≥ 1 of the following: T3-T4, Gleason ≥8, PSA ≥20 ng/mL, pN + (stratification factors). All 413 patients had a staging pelvic lymph node dissection. Patients were randomized to goserelin for 3 years and 4 cycles of docetaxel 70 mg/m2 + estramustine 10 mg/kg/d days 1-5, every 3 weeks (ADT+DE arm) or goserelin alone (ADT arm). Local therapy (radiotherapy: 87%) was administered at 3 months. Outcomes were tested with a pre-specified order (1: RFS, 2: clinical RFS (cRFS), and 3: metastases-free survival (MFS)) by the fixed-sequence method for controlling the family-wise error rate when conducting tests for multiple endpoints. RFS events: biochemical failures, metastases, proven local relapses, use of salvage treatment, and deaths. cRFS events: metastases, proven local relapses, and deaths. MFS events: metastases and deaths.
With a median follow-up of 12 years [95% CI 11.9–12.2], 233 patients (56%) have had an event. RFS was improved in the ADT+DE arm: 12-year RFS rate: 49.4% [42.5%; 56.3%] in the ADT+DE arm vs 36.3% [29.7%; 43.5%] in the ADT arm (adjusted HR: 0.71 [0.55; 0.93], p = 0.01). The median RFS was 11.6 [9.1; NR] and 8.1 [7.3; 9.6] years. cRFS was also significantly improved in the ADT+DE arm (adjusted HR: 0.75 [0.56 ; 1.00]; p = 0.0491); 12-year rates: 58.8% [51.7% ; 65.6%] vs 50.5% [43.4% ; 57.6%]; median cRFS: 13.9 (13.3-14.9) vs 12.5 (9.9-15.3) years. 12-year MFS rates were 62.2% [55.1%; 68.8%] and 55.8% [48.6%; 62.8%] (adjusted HR: 0.81 [0.60; 1.09]. 12-year PC-specific survival rates were 88.2% [82.5%; 92.2%] and 83.9% [77.4%; 88.8%] (adjusted HR: 0.70 [0.40; 1.22]). The 12-year cumulative rates of second cancers (16.4% vs 18.8%) were similar.
Four cycles of docetaxel-based chemotherapy reduces the risk of clinical relapse or death in men with high-risk localized prostate cancer.
Clinical trial identification
Legal entity responsible for the study
K. Fizazi: Advisory boards, honorarium: Sanofi. F. Joly: Advisory boards: Sanofi. G. Gravis: Travel expense: Sanofi, Janssen, Astellas. L. Mourey: Travel expense, honoraria: Sanofi. All other authors have declared no conflicts of interest.