Hypofractionated Dose Escalation Radiotherapy for High-Risk Prostate Cancer: the survival analysis of the Prostate Cancer Study-5 (PCS-5), a GROUQ-led phase III trial

Abstract

Background and objective: Prostate Cancer Study 5 (PCS5) compared conventional fractionated radiotherapy (CFRT) with hypofractionated radiotherapy (HFRT) in high-risk prostate cancer (PCa) patients, hypothesizing similar toxicity and survival outcomes. This report presents the efficacy analysis.

Methods: PCS5 is a Canadian multicenter, open-label, phase 3 randomized control trial. Men with histologically proven, clinically localized PCa with one or more high-risk features (T3/T4, Gleason score ≥8, and prostate-specific antigen >20) were eligible. Patients were randomized 1:1 to CFRT (76 Gy/38 fractions [Fx] to the prostate and 46 Gy/23 Fx to the pelvic lymph nodes [PLNs]) or HFRT (68 Gy/25 Fx to the prostate and 45 Gy/25 Fx to the PLNs) and 28 mo of androgen suppression. The primary endpoint was toxicity; secondary endpoints included survival outcomes.

Key findings and limitations: Of 329 patients, 164 were randomized to HFRT and 165 to CFRT, with 159 in the HFRT arm and 160 in the CFRT arm included in survival analyses. At the 5-yr median follow-up, there were no significant differences in overall survival (OS; 90.3% vs 89.7%; risk ratio [RR]: 1.01; 95% confidence interval [CI]: 0.93-1.09), PCa-specific survival (PCSS; 97.4% vs 97.5%; RR: 1.00; 95% CI: 0.93-1.07), biochemical recurrence-free survival (BCRFS; 85.2% vs 85.2%; RR: 1.00; 95% CI: 0.91-1.10), or distant metastasis-free survival (DMFS; 87.1% vs 87.1%; RR: 1.00; 95% CI: 0.92-1.09). Hazard ratios were 0.92 (95% CI: 0.56-1.53) for OS, 1.31 (95% CI: 0.46-3.78) for PCSS, 0.85 (95% CI: 0.56-1.30) for BCRFS, and 0.90 (95% CI: 0.56-1.43) for DMFS. Sample size was a limiting factor.

Conclusions and clinical implications: There were no differences in survival outcomes between HFRT (68 Gy/25 Fx) and CFRT (76 Gy/38 Fx). HFRT, including PLN radiotherapy and long-term androgen deprivation therapy, should be considered a new standard of care for high-risk PCa patients undergoing external beam radiotherapy.

Keywords: Hypofractionated radiotherapy; Long-term androgen suppression; Pelvic radiation therapy; Prostate cancer.