Salvage stereotactic body radiotherapy for post-prostatectomy recurrence: are we almost there?

The use of hypofractionated radiotherapy (HFRT) after prostatectomy has expanded because of its radiobiological advantages and its potential to reduce treatment burden. Stereotactic body radiotherapy (SBRT), an even more condensed treatment approach, has recently emerged as a possible salvage option for men with biochemical recurrence, although its role remains investigational. To summarize current evidence, we performed a narrative review of published and ongoing studies evaluating moderate HFRT and SBRT for prostate bed salvage radiotherapy, drawing from MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through May 2025. Across the available literature, moderate HFRT using 2.5-3.0 Gy per fraction over 15-28 fractions has shown favorable tumor control with generally acceptable safety, though some studies report increased late genitourinary toxicity with higher per-fraction doses or wide treatment margins. The phase III NRG-GU003 trial demonstrated non-inferiority of HFRT compared with conventional radiotherapy using patient-reported outcomes, supporting its clinical validity. Early SBRT experiences, often using 30-34 Gy in five fractions, have shown grade ≥ 2 genitourinary toxicity in up to approximately 29% of patients, while gastrointestinal toxicity has typically remained low. However, follow-up is short, and long-term safety remains uncertain. Although conventionally fractionated salvage radiotherapy remains the standard of care, current evidence supports moderate HFRT as an accepted alternative to conventional fractionation, whereas postoperative SBRT may be feasible in selected patients. Given limited long-term safety data and the potential for late toxicities to emerge many years after treatment, SBRT should remain investigational until results from ongoing trials become available.