Development and internal validation of a multivariable prediction model for Gleason score upgrading after radical prostatectomy in patients with biopsy ISUP Grade Group 1 prostate cancer.

Background: Biopsy-confirmed International Society of Urological Pathology (ISUP) Grade Group 1 prostate cancer (PCa) is often considered suitable for active surveillance (AS). However, postoperative Gleason score upgrading (GSU) remains a major source of uncertainty in selected patients who proceed to radical prostatectomy (RP). This study aimed to develop and internally validate a multivariable model for predicting postoperative GSU in men with biopsy-confirmed Gleason score 3+3=6 disease who underwent RP. Methods: We retrospectively reviewed patients who underwent transperineal prostate biopsy followed by RP at Northern Jiangsu People's Hospital Affiliated to Yangzhou University between October 2022 and May 2025. Patients with biopsy Gleason score 3+3=6 and no preoperative evidence of metastasis were included; patients with prior androgen-deprivation therapy or chemotherapy, incomplete key data, coexisting malignancy, or active inflammatory/infectious disease were excluded. Candidate predictors included demographic, laboratory, imaging, pathological, and clinical variables. The reference standard for GSU was final RP pathology, with GSU defined as ISUP Grade Group 2 or higher. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. Variables associated with GSU in preliminary analysis and considered clinically plausible were entered into least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable logistic regression for effect estimation and nomogram construction. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, the Hosmer-Lemeshow test, decision curve analysis (DCA), threshold-based classification metrics, and bootstrap internal validation. Results: Among 312 patients, 143 (45.9%) had postoperative GSU. The median age was 72 years, and the median prostate-specific antigen (PSA) level was 9.00 ng/mL. In multivariable analysis, age [odds ratio (OR) =1.06, 95% confidence interval (CI): 1.02-1.11], percentage of positive biopsy cores (OR =1.05, 95% CI: 1.03-1.08), and Prostate Imaging Reporting and Data System (PI-RADS) score ≥4 (OR =2.26, 95% CI: 1.22-4.21) were independently associated with GSU. The nomogram showed AUCs of 0.78 (95% CI: 0.72-0.84) in the training cohort and 0.73 (95% CI: 0.63-0.83) in the validation cohort. At the Youden-index cutoff, sensitivity/specificity were 0.87/0.53 in the training cohort and 0.90/0.40 in the validation cohort, with acceptable calibration and net clinical benefit across clinically relevant threshold ranges. Conclusions: This internally validated model provides a quantitative adjunct for estimating the probability of postoperative GSU in biopsy ISUP Grade Group 1 patients undergoing RP. Because the cohort was derived from a single center and lacked external validation, the model should be interpreted as exploratory and requires prospective multicenter validation before routine clinical use.