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Karl Heinrich Tully, Maximilian Schulmeyer, Julian Hanske, Moritz Reike, Marko Brock, Rudolf Moritz, Hendrik Jan Jütte, Andrea Tannapfel, Christian von Bodman, Joachim Noldus, Rein-Jüri Palisaar, Florian Bernhard Gerhard Roghmann

• \(\bf Objective\) To identify patients at risk for biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) with intra-operative whole-mount frozen section (FS) of the prostate. \(\textbf {Material and Methods}\) We examined differences in BCR between patients with initial negative surgical margins at FS, patients with final negative surgical margins with initial positive margins at FS without residual PCa after secondary tumour resection, and patients with final negative surgical margins with initially positive margins at FS with residual PCa in the secondary tumour resection specimen. Institutional data of 883 consecutive patients undergoing RP were collected. Intra-operative whole-mount FS was routinely used to check for margin status and, if necessary, to resect more periprostatic tissue in order to achieve negative margins. Patients with lymph node-positive disease or final positive surgical margins were excluded from the analysis. Kaplan−Meier curves and multivariable Cox proportional hazards regression analyses adjusting for clinical covariates were employed to examine differences in biochemical recurrence-free survival (BRFS) according to the resection status mentioned above. \(\bf Results\) The median follow-up was 22.4 months. The 1- and 2-year BRFS rates in patients with (81.0% and 72.9%, respectively; \(\it P\) = 0.001) and without residual PCa (90.3% and 82.3%, respectively; \(\it P\) = 0.033) after secondary tumour resection were significantly lower compared to patients with initial R0 status (93.4% and 90.9%, respectively). On multivariable Cox regression only residual PCa in the secondary tumour resection was associated with a higher risk of BCR compared to initial R0 status (hazard ratio 1.99, 95% confidence interval 1.01–3.92; \(\it P\) = 0.046). \(\bf Conclusion\) Despite being classified as having a negative surgical margin, patients with residual PCa in the secondary tumour resection specimen face a high risk of BCR. These findings warrant closer post-RP surveillance of this particular subgroup. Further research of this high-risk subset of patients should focus on examining whether these patients benefit from early salvage therapy and how resection status impacts oncological outcomes in the changing landscape of PCa treatment.