A standard therapy has not been established on PSA failure after radical prostatectomy for localized prostate cancer. Therefore, the randomized controlled trial was designed to confirm the superiority of radiotherapy ± endocrine therapy over endocrine therapy alone for PSA failure after radical prostatectomy.
Patients were randomly assigned to arm A [endocrine therapy only: bicalutamide (BCL) monotherapy followed by LH-RH agonist in case of BCL failure], or arm B [64.8 Gy of salvage radiotherapy (SRT) followed by same regimen of arm A in case of treatment failure of SRT]. The primary endpoint is time to treatment failure (TTF) of BCL, and secondary endpoints are TTF of protocol treatment, clinical relapse-free survival (RFS), overall survival (OS), adverse events. The planned sample size was 210 to detect improvement of median TTF of BCL from 5 years to 8.3 years with one-sided alpha of 5% and power of 80%. This trial is registered with UMIN-CTR (C000000026).
A total of 210 patients (105 patients in each arm) were registered from May 2004 to May 2011. The TTF of BCL was significantly better in arm B as shown in Table 1 (Hazard ratio 0.56 90% CI (0.40–0.77); one-sided p = 0.001). The 33 patients (32%) of 102 patients with SRT of arm B had no treatment failure of SRT, resulting in being free from hormonal therapy. In addition, TTF of protocol treatment was also significantly better in arm B. However, clinical RFS and OS were similar between the arms. Grade 4 adverse event was reported in one patient in arm B.Table:
|Arm A||Arm B||Hazard Ratio (95% CI)|
|(endocrine therapy only) (95% CI)||(radiation +/- endocrine therapy) (95% CI)|
|5-year TTF of BCL||57.0% (46.7%–66.0%)||69.7% (59.6%–77.7%)||0.56 (0.38-0.82)|
|5-year TTF of protocol treatment||67.0% (56.9%–75.3%)||76.8% (67.1%–83.9%)||0.66 (0.44-1.00)|
|5-year clinical RFS||93.8% (86.8%–97.2%)||88.9% (80.9%–93.7%)||0.90 (0.45-1.81)|
|5-year OS||99.0% (93.4%–99.9%)||91.4% (84.2%–95.4%)||1.03 (0.46-2.29)|
The first SRT had advantage in both TTF of BCL and protocol treatment. Although the clinical outcomes of both arms of salvage therapy were similar with each other in terms of clinical PFS and OS, the SRT was effective in 32% of the patients, which contributed to avoiding the salvage endocrine therapy.
Clinical trial identification
Legal entity responsible for the study
Japan Clinical Oncology Group, JCOG
Ministry of Health, Labor and Welfare of Japan
A. Yokomizo: Lecture fee from Astellas Pharma Inc., AstraZeneca K.K.and Takeda Pharmaceutical Company Limited. T. Satoh: lecture fee from Bayer AG, Astellas Pharma Inc., and AstraZeneca K.K. K. Hashine: lecture fee from Astellas Pharma Inc., Sanofi, Takeda Phrmaceutical Co.Ltd., Brystol Myers, AstraZeneca and Janssen Pharma. T. Inoue: lecture fee from Astellas Pharma Inc., AstraZeneca K.K.and Janssen Pharma K.K. K. Fujimoto: lecture fee from AstraZeneca K.K.and Takeda Pharmaceutical Company Limited S. Egawa: AstraZeneca, Astellas, Takeda Pharma Co. O. Ishizuka: Research grant from Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Pfizar Japan Inc. Lecture fee from Astellas Pharma Inc. N. Shinohara: Lecture fee from Bayer Co., Astellas Pharma Inc., Pfizer, and Novartis. .Advisary fee from Ono Pharma Inc. and Takeda Pharma. Co. S. Naito: Personal financial interest from Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd. and Green Peptide Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.