PSMA PET/CT-guided salvage elective nodal radiotherapy for nodal metastases after radical prostatectomy: a bi-institutional long-term outcome analysis

Purpose PSMA PET/CT has transformed the detection of nodal recurrence after radical prostatectomy, yet real-world evidence on long-term outcomes of PSMA PET/CT-guided salvage elective nodal radiotherapy (ENRT) remains limited. This study evaluated oncological outcomes of PSMA PET/CT-guided salvage ENRT in a bi-institutional cohort with extended follow-up. Methods We retrospectively analysed 179 patients who received PSMA PET/CT-based ENRT for nodal recurrence after radical prostatectomy at two tertiary centres between 2014 and 2024. Patients with pelvic and/or paraaortic lymph node metastases were included. The primary endpoint was metastasis-free survival (MFS); secondary endpoints included biochemical progression-free survival (BPFS) and overall survival (OS). Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were assessed using Cox regression analysis. Results Of the 179 patients, 104 (58.1%) had true biochemical recurrence after radical prostatectomy, whereas 75 (41.9%) had PSA persistence. After a median follow-up of 60.3 months, 5-year MFS and BPFS rates were 74.3% and 62.3%, respectively, in patients with true biochemical recurrence, compared with 61.2% and 56.4% in the overall cohort. In multivariable analyses of the entire cohort, concomitant ADT was associated with improved MFS (HR 0.36, p < 0.001) and BPFS (HR 0.26, p < 0.001), compared with no ADT. PSA persistence after surgery was associated with worse outcomes (MFS: HR 2.72, p < 0.001; BPFS: HR 2.09, p = 0.005). Conclusion PSMA PET/CT-guided salvage ENRT predominantly combined with ADT provides durable long-term disease control in patients with nodal recurrence in routine clinical practice. In patients with true recurrence after radical prostatectomy, the 5-year MFS rate was 74.3%, approaching outcomes reported in prospective trials. However, the absence of systematically collected clinician-assessed toxicity and patient-reported outcomes precludes a reliable assessment of treatment tolerability.