Optimizing the Timing of Salvage Postprostatectomy Radiotherapy and the Use of Concurrent Hormonal Therapy for Prostate Cancer

Context: Currently, salvage radiotherapy (SRT) is the only known curative intervention for men with recurrent disease following prostatectomy. Critical issues in the optimal selection and management of men being considered for SRT include the threshold prostate-specific antigen (PSA) value at which to initiate treatment (ie, pre-SRT PSA) and the role of concurrent hormonal therapy (HT). Objective: To review the published evidence pertaining to the optimal timing for SRT and the role of concurrent HT. Evidence acquisition: MEDLINE (via PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, and guideline statements from professional organizations were queried from January 1, 2000 through January 10, 2018. Evidence synthesis: Thirty-three independent reports, including two randomized trials evaluating HT with SRT, were identified. Retrospective data suggest that SRT initiation at lower pre-SRT PSA levels is associated with better clinical outcomes. Prospective data suggest an overall survival benefit with concurrent HT that manifests during long-term follow-up, with the caveat that hypothesis-generating subgroup analyses suggest that this benefit may be limited to patients with higher pre-SRT PSA levels. Patients with adverse risk factors, such as Gleason grade group 4–5 disease, are likely to benefit the most from earlier SRT initiation and/or the use of HT. Conclusions: Given the limitations of the available data, it is imperative that physicians participate in shared decision-making, with the recommendation tailored for each man's desire to maximize oncologic benefit (with a risk of overtreatment) versus potential quality-of-life optimization (with a risk of undertreatment). Within that framework, a significant body of retrospective data supports initiation of SRT at low pre-SRT PSA values, without an arbitrary absolute threshold. Prospective data suggest a benefit of HT, but this benefit may be greatest in patients with a pre-SRT PSA that is higher than the typical level in most patients receiving “early” SRT. Further research is necessary before absolute recommendations can be made. Patient summary: Two ways to potentially improve outcomes following salvage radiotherapy for prostate cancer that recurs after prostatectomy are to start treatment at a lower prostate-specific antigen level and to use concurrent hormonal therapy. Our review suggests that the available evidence is imperfect, but highlights that both measures are likely to improve clinical outcomes in general, but perhaps not uniformly and/or consistently for all patients. Physician-patient shared decision-making and further research are critical. Outcomes following salvage radiotherapy can be optimized by starting salvage at lower prostate-specific antigen (PSA) values without an arbitrary threshold and/or by giving concurrent hormonal therapy, although the benefit of the latter may be greatest in patients with higher presalvage PSA. Physician-patient shared decision-making and further research are critical.