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.