Penalized-Survival Nomogram Predicts 5-Year Metastasis-Free Survival After Salvage Radiotherapy for Postprostatectomy Patients: A Multicenter Study

Background/Aim Salvage radiotherapy (SRT) is a key treatment for biochemical recurrence (BCR) after radical prostatectomy (RP), yet a significant proportion of patients progress to distant metastasis. This multicenter retrospective study aimed to analyze a series of patients who underwent SRT and to develop a predictive nomogram for 5-year-distant-metastasis-free survival (DMFS). Material and Methods Data were collected from 15 European centers from June 1, 2022, to September 30, 2024. We included SRT patients due to BCR, following RP and no evidence of distant metastases on imaging. A penalized-survival nomogram was developed and internally validated; external validation was performed using data from the largest center. Patients were stratified into low-, intermediate-, and high-risk groups based on tertiles of the predicted risk score distribution. Results Data from 1,720 SRT patients were analyzed. BCR after SRT occurred in 620 (37%) patients, while clinical recurrence in 494 (30%) patients. Distant metastases were diagnosed in 228 patients (13%). The 2- and 5- years DMFS rates were 93% (95% CI, 92%-95%) and 84% (95% CI, 81%-86%), respectively. Multivariate analysis identified pT3/pT4 stage (HR 1.54 [95% CI, 1.13-2.13], P < .01), ISUP grade group 4/5 (HR 1.75 [95% CI, 1.30-2.35], P < .01), and SRT <12 months from surgery (HR 1.49 [95% CI, 1.07-2.09], P = .02) as independent predictors of DM. The nomogram achieved a C-index of 0.70 in external validation. Stratification into risk groups showed significant differences in DMFS ( P < .01). Conclusions This externally validated nomogram provides a practical tool for predicting 5-year DMFS in patients undergoing SRT. It enables personalized risk assessment, guiding intensified surveillance and treatment for high-risk patients.