Predictors of ISUP Grade Group Discrepancies Between Biopsy and Radical Prostatectomy: A Single-Center Analysis of Clinical, Imaging, and Histopathological Parameters

<b>Background/Objectives</b>: ISUP grade group discordance between prostate biopsy and radical prostatectomy (RP) impacts treatment decisions in over a third (~25-40%) of prostate cancer (PCa) patients. We aimed to identify ISUP grade migration predictors and assess the impact of preoperative imaging (MRI) in a contemporary Romanian PCa cohort. <b>Methods</b>: We retrospectively analyzed 142 PCa patients undergoing RP following biopsy between January 2021 and December 2024 at Pius Brinzeu County Hospital, Timișoara: 90 without and 52 with preoperative MRI. Clinical parameters, MRI findings (PI-RADS), and biopsy characteristics were evaluated. Machine learning models (gradient boosting, random forest) were developed with SHAP analysis for interpretability. <b>Results</b>: Grade migration occurred in 69/142 patients (48.6%): upstaging in 55 (38.7%) and downstaging in 14 (9.9%). In the non-MRI cohort, 37/90 (41.1%) were upstaged and 9/90 (10.0%) were downstaged, versus 18/52 (34.6%) upstaged and 5/52 (9.6%) downstaged in the MRI cohort. The MRI group showed a 6.5% absolute reduction in upstaging (34.6% vs. 41.1%), a promising non-significant trend (<i>p</i> = 0.469) that requires further investigation. Grade 1 patients showed the highest upstaging (69.4%), while Grades 3-4 showed the highest downstaging (11/43, 25.6%). PI-RADS 4 lesions had the highest upstaging (43.5%). PSA density > 0.20 ng/mL² emerged as the strongest predictor. Gradient boosting achieved superior performance (AUC = 0.812) versus logistic regression (AUC = 0.721), representing a 13% improvement in discrimination. SHAP analysis revealed PSA density as the most influential (importance: 0.287). Grade migration associated with adverse pathology: extracapsular extension (52.7% vs. 28.7%, <i>p</i> = 0.008) and positive margins (38.2% vs. 21.8%, <i>p</i> = 0.045). <b>Conclusions</b>: ISUP grade migration affects 48.6% of Romanian patients, with 38.7% upstaged and 9.9% downstaged. The 69.4% upstaging in Grade 1 patients emphasizes the need for enhanced risk stratification tools, while 10% downstaging suggests potential overtreatment. Machine learning with SHAP analysis provides superior predictive performance (13% AUC improvement) while offering clinically interpretable risk assessments. PSA density dominates risk assessment, while PI-RADS 4 lesions warrant closer scrutiny than previously recognized.