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BACKGROUND Mitomycin C (MMC) is widely used, but the optimal dose and schedule have not been established. OBJECTIVE To evaluate the ablative power and patient safety of a short-term intensive schedule of intravesical MMC in patients with recurrent non-muscle-invasive bladder cancer (NMIBC). DESIGN, SETTING, AND PARTICIPANTS This was a prospective, single-center, nonrandomized study that compared 47 patients (group 1) with a history of low- to intermediate-risk NMIBC with long free-recurrence intervals, recurrence of ≤1cm in maximum diameter, and negative cytology to 47 consecutive patients with the same baseline characteristics (group 2). INTERVENTION Intravesical MMC three times per week for 2 wk for group 1. Transurethral resection of bladder tumor (TUR-BT) and early instillation and a weekly schedule of intravesical MMC for group 2. All cancer-free patients underwent monthly MMC maintenance. Follow-up included bladder mapping, voiding and washing urinary cytology, TUR of suspected area, TUR of previous tumor location, and ultrasound or computed tomography/magnetic resonance imaging. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS We used χ2 and Student's t test for comparison of categorical and continuous variables, respectively. Kaplan-Meier curves were plotted to estimate cancer-free survival. The significance level was set to p<0.05. RESULTS AND LIMITATIONS The complete response rate at 39 mo was 61.7% in group 1 and 70.2% in group 2 (p=0.38). Kaplan-Mayer analysis revealed no difference in cancer-free survival rates overall (log-rank <3.84), according to tumor size in each group (log-rank <3.84), or between the groups (log-rank <7.82). No cases of systemic toxicity were observed. Local toxicities did not differ between the groups (p=0.32) and resolved on treatment of symptoms, and no patient discontinued their treatment. Limitations include the small number of patients, selection bias because of the single tertiary center, and short follow-up. CONCLUSIONS The proposed MMC schedule had good ablative power that can be explained by better concordance between the scheduled timing and the tumor cell duplication rate. The short-term intensive schedule could be considered as a therapeutic strategy to replace TUR-BT in selected NMIBC patients. PATIENT SUMMARY We report our experience of a tailored intravesical therapy schedule for bladder cancer. This schedule could be considered a therapeutic strategy to replace surgery for selected patients.