Clinical outcomes of neoadjuvant intravesical mitomycin-C therapy administered immediately prior to TURBT in NMIBC: Over three years of follow-up data from a randomized phase II trial.

771 Background: Immediate neoadjuvant intravesical chemotherapy (INAIC) with mitomycin C (MMC), administered before transurethral resection of bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients, may prevent reimplantation of free-floating cancer cells dislodged during piecemeal resection by reducing their tumorigenic potential preoperatively and increasing MMC concentration in the resected tumor bed. We previously reported per-protocol analysis that showed a 63% recurrence risk reduction with our strategy versus TURBT alone, though not statistically significant (P = 0.11), likely due to limited follow-up (PMID: 36250938). We updated our preliminary analysis to include oncological outcomes over three years for assessing the strategy's long-term sustainability. Methods: This single-center, randomized phase II trial was conducted at the National Cancer Center of South Korea between August 2016 and December 2020 (IRB No. NCC2016-0168). The intervention group received two 40 mg/20 mL doses of MMC one day before and four hours prior to TURBT. The control group underwent standard TURBT only; no patients in either group received immediate post-operative intravesical chemotherapy (IPOIC). The primary endpoint was three-year RFS; secondary endpoints included independent risk factors for recurrence, progression-free survival (PFS), and cystectomy-free survival (CFS). Statistical analyses used two-tailed tests, with p-values 0.05). During a prolonged follow-up period, recurrence occurred in 9.1% (3/33) in the intervention group vs. 31.5% (12/38) of controls. Two INAIC doses with MMC cut recurrence risk by 77% vs. TURBT alone, with 3- and 5-year RFS rates of 90.7% vs. 78.6% and 75.3%, respectively, confirming sustained benefits (P = 0.01). During follow-up, 15.8% (6/38) of control patients progressed and 7.8% (3/33) had cystectomy (ypT0N0, ypT2N0, pT1N0); none in the intervention group did. Two doses of INAIC with MMC significantly improved 3- and 5-year PFS rates compared to controls (100% vs. 92.1% and 85.8%; HR 0.078, P = 0.014) and 3- and 5-year CFS rates (100% vs. 97.4% and 91.1%; HR 0.078, P = 0.014) using Firth’s penalized likelihood method. Conclusions: Our up-to-date analysis further supports using INAIC with two MMC doses for favorable mid- to long-term oncological outcomes in diverse NMIBC patients. Clinical trial information: NCT03058757 .