Dose-intensified Versus Conventional-dose Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: The SAKK 09/10 Randomized Phase 3 Trial.

BACKGROUND:Salvage radiotherapy (SRT) is utilized for biochemical progression of prostate cancer after radical prostatectomy (RP). OBJECTIVE:To report the outcomes of the SAKK 09/10 trial comparing conventional and dose-intensified SRT. DESIGN, SETTING, AND PARTICIPANTS:SAKK 09/10 was a randomized, multicenter, phase 3 trial that recruited men with biochemical progression after RP. INTERVENTION:Patients were randomly assigned to conventional-dose (64 Gy) or dose-intensified SRT (70 Gy) to the prostate bed without hormonal therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary endpoint was freedom from biochemical progression (FFBP). Secondary endpoints included clinical progression-free survival (PFS), time to hormonal treatment, overall survival (OS), acute and late toxicity (Common Terminology Criteria for Adverse Events v4.0), and quality of life (QoL). RESULTS AND LIMITATIONS:Between February 2011 and April 2014, 350 patients were randomly assigned to 64 Gy (n = 175) or 70 Gy (n = 175). Median prostate-specific antigen at randomization was 0.3 ng/ml. After median follow-up of 6.2 yr, the median FFBP was 8.2 yr in the 64 Gy arm and 7.6 in the 70 Gy arm (log-rank p = 0.4), with a hazard ratio of 1.14 (95% confidence interval 0.82-1.60). The 6-year FFBP rates were 62% and 61%, respectively. No significant differences in clinical PFS, time to hormonal treatment, or OS were observed. Late grade 2 and 3 genitourinary toxicity was observed in 35 (21%) and 13 (7.9%) patients in the 64 Gy arm, and 46 (26%) and seven (4%) in the 70 Gy arm, respectively (p = 0.8). Late grade 2 and 3 gastrointestinal toxicity was observed in 12 (7.3%) and seven patients (4.2%) in the 64 Gy arm, and 35 (20%) and four (2.3%) in the 70 Gy arm, respectively (p = 0.009). There were no significant differences in QoL. CONCLUSIONS:Conventional-dose SRT to the prostate bed is sufficient in patients with early biochemical progression of prostate cancer after RP. PATIENT SUMMARY:The optimal radiation therapy dose for patients who have increased tumor markers after surgery for prostate cancer is unclear. We found that administering a higher dose only increased the gastrointestinal side effects without providing any benefits to the patient. This clinical trial is registered on ClinicalTrials.gov as NCT01272050.