Introduction: Although cystoscopy is highly accurate in managing bladder cancer, its invasive nature and high cost underscore the need for more practical, noninvasive alternatives. Urinary Twist Family BHLH Transcription Factor 1 (Twist1) methylation, an emerging biomarker, shows great promise for early diagnosis and postsurgical monitoring. Meanwhile, the Vesical Imaging-Reporting and Data System (VI-RADS), which incorporates multiple sequences of multiparametric MRI, demonstrates excellent diagnostic performance for bladder cancer. These tools could potentially overcome the limitations in managing non-muscle invasive bladder cancer (NMIBC), particularly in predicting residual tumor burden before repeat transurethral resection of bladder tumor (re-TURBT). This study aims to evaluate a predictive model that combines VI-RADS, urinary Twist1 methylation, and hematuria to guide clinical decision-making in NMIBC management. Methods: A prospective cohort study was conducted, including NMIBC patients who underwent re-TURBT at the Department of Urology, Zhongshan city People’s Hospital, from June 2022 to May 2024. Morning urine samples were collected prior to re-TURBT to detect urinary Twist1 methylation, and a 3.0T MRI scan of the bladder was performed for VI-RADS scoring. Based on postoperative pathology results, patients were divided into residual tumor and non-residual tumor groups. Binary logistic regression was employed to identify independent predictors of residual tumor burden prior to re-TURBT. Two predictive models were subsequently developed. The diagnostic performance and clinical utility of these models were assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: The study ultimately included 52 patients who were initially diagnosed with NMIBC based on pathology. According to the pathological results after re-TURBT, the patients were divided into two groups: the tumor residue group (n = 22) and the control group (n = 30). Binary logistic regression analysis identified the VI-RADS score and urinary Twist1 methylation as independent predictors of residual tumor burden in NMIBC patients prior to re-TURBT. A predictive model incorporating these factors, along with the presence of visible hematuria within 1 week before re-TURBT, achieved a sensitivity of 95.45% and a specificity of 83.33% for diagnosing residual tumor burden. ROC curve analysis demonstrated an area under the curve (AUC) of 0.950 (95% CI: 0.884–1.000, p < 0.001). DCA revealed that the model provided a net benefit for threshold probabilities ranging from 0.10 to 0.92. Conclusion: The predictive model combining VI-RADS score, urinary Twist1 methylation, and visible hematuria exhibits excellent diagnostic performance for predicting residual tumor burden in NMIBC patients, offering significant guidance for clinical practice.

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