Risk factors for incidental prostate cancer following surgery for benign prostatic enlargement: A systematic review and meta-analysis

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Abstract
Background Incidental prostate cancer (IPC) is not uncommon in patients undergoing surgery for benign prostate enlargement (BPE). However, the associated risk factors remain incompletely understood. This study aimed to evaluate potential clinical predictors of IPC. Methods A systematic search of MEDLINE, Embase, and Web of Science was conducted in January 2025 to identify studies assessing risk factors for IPC. Pairwise meta-analyses were performed using a random-effects model, pooling adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable analyses. Risk of bias was evaluated using the ROBINS-I tool. (PROSPERO: CRD42024588776). Results Twenty-five studies comprising 247,966 patients were included. IPC was identified in 6,748 patients, with reported rates ranging from 2.2% to 49.6%. Significant risk factors for IPC included: Elevated PSA level (OR: 1.03; 95% CI: 1.01–1.05; p = 0.01), PSA density >0.15 ng/mL/cc (OR: 3.02; 95% CI: 1.50–6.07; p = 0.01), Older age (OR: 1.05; 95% CI: 1.01–1.08; p = 0.01), and Higher body mass index (BMI) (OR: 1.10; 95% CI: 1.02–1.18; p = 0.01). Prostate volume, diabetes, and dyslipidemia were not associated with IPC risk. Notably, use of 5-alpha reductase inhibitors (5-ARIs) was linked to a significantly reduced risk (OR: 0.53; 95% CI: 0.33–0.85; p = 0.01). Study limitations included heterogeneity across studies, retrospective designs, and incomplete reporting of key variables. Conclusions Elevated PSA, high PSA density, older age, and increased BMI were associated with a higher risk of IPC in patients undergoing surgery for BPE. Conversely, preoperative use of 5-ARIs was associated with a reduced risk. These findings may support improved preoperative risk stratification and help identify patients in whom additional diagnostic evaluations could be considered or avoided. Further research is needed to better define predictors of clinically significant IPC.

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