Optimal timing of salvage radiotherapy after radical prostatectomy with or without hormone therapy and/or whole pelvic radiotherapy

Abstract Purpose To determine the optimal time for salvage radiotherapy (SRT) after radical prostatectomy (RP) with or without hormone therapy (HT) and/or whole pelvic radiotherapy (WPRT) by balancing radiotherapy-related toxicity and tumor control. Methods Data from 155 prostate cancer (PCa) patients who received salvage radiotherapy (SRT) following radical prostatectomy (RP) between April 2015 and February 2021 were analyzed. Early salvage radiotherapy (ESRT) was defined as prostate-specific antigen (PSA) ≤ 0.5 ng/ml before radiotherapy. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events, version 5.0. Survival outcomes were analyzed using the Kaplan–Meier estimates and Cox proportional-hazards regression. Progression-free survival (PFS) and overall survival (OS) were assessed. Results Patients who received ESRT had significantly higher 5-year PFS (83.8%) compared to those who received late SRT (LSRT) + HT or WPRT (42.8%) and LSRT + HT + WPRT (25.2%) ( p < 0.001). Time from RP to SRT (TFRTS) and WPRT were significant predictors of both acute (OR: 0.963, p = 0.006; OR: 2.244, p = 0.043) and late genitourinary (GU) toxicities (OR: 0.772, p = 0.001; OR: 3.816, p = 0.037). A decrease of 1.1% in acute GU toxicity probability for each incremental 2 months after RP, and a decrease of 2.2% in late GU toxicity probability for every additional month within 28 months after RP was observed. For every three months increase in TFRTS, the incidence rate of clinical recurrence increased by 1%. The probability of clinical recurrence and late GU intersected at 12 months after RP. Conclusion The increase in treatment intensity could not compensate for the loss caused by delayed radiotherapy. To balance the toxicity and tumor control, we recommend SRT for patients with PSA persistence and early biochemical recurrence (BCR) (< 1 year) when postoperative complications resolve, and SRT for patients with late BCR (≥ 1 year) as soon as possible.