Background: To demonstrate the feasibility of resecting isolated locally relapsing seminal vesicle remnants after primary radical prostatectomy and radiotherapy. Early oncologic outcomes and prognostic risk factors for relapse are demonstrated. Objectives and Methods: A total of 32 patients underwent open resection of locoregional prostate cancer recurrence in seminal vesicles, as documented on either MRI, 11C-choline, or 68Ga-PSMA PET/CT scans. Age, PSA-DT, PSA, and time to recurrence after primary treatment resection status were used in a uni- and multivariate Cox regression analysis for biochemical relapse after surgery. Results: Median patient age at time of salvage surgery was 70 (57–77) years. Median PSA and PSA-DT was 2.79 (0.4–61.54) ng/mL and 5.4 (1.6–20.1) months, respectively. Median surgical time and hospital stay was 132 (75–313) min and 5.5 (4–13) days, respectively. After a mean follow-up of 29 (2–92) months, 3 patients died at 8, 14, and 40 months after salvage surgery, and 6 (18.75%) patients remain without biochemical relapse and further treatment. Median progression-free survival was 12 (1–81) months. In the univariable Cox regression analysis, age at time of surgery, preoperative PSA, and the time from primary treatment to salvage surgery were identified as significant parameters for biochemical relapse. Only the interval from primary to salvage surgery was significant in the multivariate analysis with a hazard ratio of 1.008 (95% CI: 1.001–1.015, p = 0.018). In the entire cohort, 4 adjunctive surgeries (3 ureteroneocystostomies and 1 nephrectomy) were needed due to local progressive disease. Conclusion: Seminal vesicle resection is feasible with no significant intra- or postoperative complications. Almost all patients progressed to biochemical or systemic relapse. Salvage surgery must be seen as a preventive for local symptoms, in our experience most often postrenal ipsilateral obstruction.

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