Impact of radiation dose on recurrence in high-risk prostate cancer patients

Background Dose escalated radiation therapy (RT) combined with long-term androgen deprivation therapy (ADT) is a standard of care option for men with high-risk and locally advanced prostate cancer (PCa). However, the optimal dose of escalated RT and ADT is not known. Here we assessed the impact of radiation dose and length of ADT on biochemical recurrence in a multi-institutional cohort stratified by the Cambridge prognostic group (CPG). We hypothesized that radiation dose and length of ADT would impact outcome in similar risk groups of our patients. Methods Two-hundred and forty-four patients were included, 132 from Oslo University Hospital, Department of Oncology and 112 from Johns Hopkins Hospital, Department of Radiation Oncology. Biochemical recurrence was defined as prostate-specific antigen (PSA) nadir +2 ng/mL. Time to recurrence was estimated using Kaplan-Meier analysis and when stratified by CPG the log-rank test was used. Cox regression analysis was performed to identify factors associated with risk of recurrence. Site of recurrence was investigated. Results The median follow-up time was 7.4 years. The vast majority (71%) of patients were classified as high-risk (CPG 4) or very high-risk features (CPG 5). Significantly more PSA recurrences occurred in CPG 5 (41%) compared with CPG 4 (25%) (P = .04) and five-year cumulative recurrence-free survival was lower for CPG 4 and 5 (89% and 68%) compared with CPG 1, 2, and 3 (100%, 100%, and 93%). The recurrence-free survival for CPG 5 was significantly higher for prostate irradiation of 80 Gy as compared with 74 Gy (P = .011). For CPG 4 and 5 no local recurrences were detected in patients receiving 80 Gy. On stepwise Cox regression analysis neither age nor length of ADT were independent prognostic factors for recurrence free survival. Conclusion Prostate dose escalation from 74 to 80 Gy decreases risk of recurrence in high-risk PCa. Further studies are needed to identify the optimal combination of ADT and RT.