Efficacy of Postoperative Radiation in a Prostatectomy Cohort Adjusted for Clinical and Genomic Risk

Abstract

BACKGROUND: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF). METHODS: 422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n = 111), minimal residual disease (MRD) SRT (n = 70) and SRT (n = 83) were defined by PSA levels of o 0.2, 0.2-0.49 and ⩾ 0.5 ng ml − 1 , respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome. RESULTS: During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P o0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P = 0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. CONCLUSIONS: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials. Prostate Cancer and Prostatic Diseases INTRODUCTIONAggressive treatment approaches that have not yet been shown to improve overall survival are controversial within oncology, particularly in the management of men with prostate cancer (PCa). 1,2 Three randomized clinical trials in men with nonmetastatic PCa following surgical resection showed that treatment with adjuvant radiation therapy (ART) as compared with observation resulted in lower rates of biochemical recurrence, yet had conflicting impact on metastasis-free and overall survival. [3][4][5] Given the disparate findings, there has been an increase in utilization of salvage radiation therapy (SRT) 6 with concomitant decrease in ART, despite no randomized prospective trial evidence supporting this clinical decision. Although multiple randomized clinical trials are ongoing, 7,8 results are not expected for several years. Thus, patients and physicians are left with mu...