Introduction: Accurate prediction of side-specific extraprostatic extension (ssEPE) is critical for performing nerve-sparing surgery to mitigate treatment-related side effects in patients with localized prostate cancer. Artificial intelligence (AI) may provide more personalized ssEPE predictions to better inform nerve-sparing strategy during radical prostatectomy. Methods: 4936 prostatic lobes (cases) were included. SEPERA, an AI-based Side-specific Extra-Prostatic Extension Risk Assessment tool, was trained on 1022 cases from a community network, Trillium Health Partners, Canada. SEPERA was validated on 3914 cases from three academic centers: Princess Margaret Cancer Centre, Canada; L’Institut Mutualiste Montsouris, France; and Jules Bordet Institute, Belgium. Performance was assessed by area under receiver-operating characteristic curve (AUROC), area under precision-recall curve (AUPRC), calibration, and net benefit. An algorithmic audit was conducted to assess model bias and identify common characteristics among predictive errors. SEPERA was compared against contemporary nomograms, as well as a separate logistic regression model using the same variables from SEPERA. Results: SEPERA was well calibrated and had the best performance across all validation cohorts (Table 1), enabling more patients to safely undergo nerve-sparing. No significant difference in AUROC was observed when stratified by race, biopsy year, age, biopsy type (systematic only vs systematic and MRI-targeted), biopsy location (academic vs community), and D’Amico risk group. In patients with pathological ssEPE despite benign ipsilateral biopsies, SEPERA correctly predicted ssEPE in 68% of cases, compared to 0-44% for other models. The most common errors were false positives, particularly for older patients with higher risk disease. No aggressive tumours (i.e., > Grade Group 2 or high-risk disease) were found among false negatives. Conclusions: We show the accuracy, safety, and generalizability of SEPERA – a novel AI-based assessment tool to personalize nerve-sparing approaches during radical prostatectomy. SEPERA is available at https://sepera.streamlitapp.com/. SOURCE OF Funding: None
