Pre-treatment PSA, margin status and pelvic nodal fields predict long-term outcomes in post-prostatectomy salvage radiotherapy

Background Salvage radiotherapy (SRT) is the preferred approach for biochemical recurrence (BCR) following prostatectomy; however, the optimal timing, impact of surgical margin status, and role of pelvic nodal radiotherapy (PLNRT) are not well defined. Methods We retrospectively analyzed 196 patients treated with SRT at a single institution between 2005–2013. Patients with metastatic disease, nodal involvement at surgery, or prior adjuvant RT were excluded. Primary outcomes (biochemical progression-free survival, bPFS) and secondary outcomes (PSA-response failure; metastasis-free survival, MFS; nodal recurrence-free survival, NRFS) were assessed using Kaplan-Meier, univariate and multivariate Cox regression analyses. Patients were stratified by pre-SRT PSA (≤0.2 vs >0.2 ng/mL), Gleason score, pathologic T-stage, and surgical margin status to determine association with outcomes following treatment with prostate bed-directed radiotherapy (PBRT) with or without PLNRT and/or ADT. Results A total of 196 patients undergoing salvage radiotherapy (SRT) after prostatectomy were analyzed with a median follow-up of 109.5 months. Pre-SRT PSA >0.2 ng/mL, higher Gleason score, and advanced T-stage were associated with significantly worse biochemical progression-free survival (bPFS). Margin-positive patients demonstrated improved bPFS compared to margin-negative patients. While pelvic nodal radiotherapy (PLNRT) did not improve bPFS outcomes in the aggregate cohort, margin-negative patients receiving PLNRT demonstrated significantly improved bPFS (HR 0.45, p=0.024) with significantly lower PSA-response failure rates after SRT (4.5% vs 31.7%, p=0.010). Multivariable analysis identified PLNRT as independently associated with improved nodal recurrence-free survival (NRFS) (HR 0.29, p=0.028), supporting occult regional disease as a contributor to recurrence in margin-negative patients. Conclusions SRT outcomes are heterogeneous and strongly influenced by pre-SRT PSA and surgical margin status. Early SRT at low PSA levels is associated with improved outcomes. Margin-negative patients appear to derive significant benefit from PLNRT, suggesting a distinct pattern of disease recurrence, supporting a risk-adapted approach to treatment intensification.