Two preoperative doses of intravesical mitomycin-C administered 1 day and 4 hours before transurethral resection of bladder tumor (TURBT) were associated with a 77% reduction in the risk of recurrence or death and no disease progression at 5 years of follow-up vs TURBT alone in patients with non–muscle-invasive bladder cancer (NMIBC), according to extended data from a randomized phase 2 trial presented at the
At a median follow-up of 60 months, the 5-year recurrence-free survival (RFS) rate was 90.7% (95% CI, 81.2%-100.0%) in the interventional arm (n = 33) vs 75.3% (95% CI, 62.4%-90.8%) in the control arm (n = 38; HR, 0.23; 95% CI, 0.06-0.83; P = .02). Recurrence events occurred in 9.1% of patients in the interventional arm (n = 3 of 33) compared with 31.6% in the control arm (n = 12 of 38). No evidence of disease progression was observed in the interventional arm, whereas 15.8% of patients (n = 6 of 38) in the control arm experienced progression (HR, 0.078; P = .014).
“When standard immediate postoperative instillation is not feasible, pre-TURBT mitomycin-C may represent a practical prophylactic strategy to reduce peri-TURBT tumor-cell reimplantation,” presenting study author Ho Kyung Seo, MD, PhD, stated. Seo is a member of the Department of Urology at the Center for Urologic Cancer, Hospital in the Division of Tumor Immunology, Research Institute, National Cancer Center in Goyang, South Korea.
TURBT remains the cornerstone of NMIBC management; however, the procedure carries an inherent risk of tumor cell dislodgement and intravesical reimplantation during resection. Current guidelines recommend a single immediate postoperative intravesical instillation to address this risk, but real-world uptake is constrained by safety concerns, particularly in patients with large or multifocal tumors. Investigators reasoned that administering mitomycin-C immediately before TURBT, while tumor cells are still anatomically contained, could reduce the viability of free-floating cells during surgical manipulation without the postoperative complications associated with instillation into a freshly resected bladder.
This single-center, open-label, randomized phase 2 trial enrolled patients aged 18 to 85 years with NMIBC, an ECOG performance status of 0 to 1, a glomerular filtration rate of 30 mL/min or greater, and normal upper urinary tract imaging within 1 year. Prior intravesical mitomycin-C within 3 years, prior hypersensitivity to mitomycin-C, neurogenic bladder, untreated urinary tract infection, and variant histology (small cell, micropapillary, or plasmacytoid carcinoma) were exclusion criteria. The study was conducted from August 2016 through December 2020.
The primary end point of the trial was 3-year RFS; progression-free survival was a secondary end point.
Patients were randomized to the interventional arm (n = 33), which received two 40-mg doses of intravesical mitomycin-C in 20 mL—one dose 1 day before TURBT and a second dose 4 hours before the procedure—or to the control arm (n = 38), which underwent TURBT alone. Neither arm received immediate postoperative instillation. Following index TURBT, repeat TURBT was performed per protocol; adjuvant intravesical therapy with BCG or mitomycin-C (induction and maintenance) and subsequent follow-up were guided by risk stratification according to current NMIBC guidelines.
Baseline characteristics were well balanced. Median age was 65 years (IQR, 56-76) in the interventional arm and 70 years (IQR, 63-76) in the control arm. High-grade disease (ISUP/WHO 2004) was present in 61% and 53% of patients, respectively; 55% of patients in each arm had pT1 disease. Tumors measuring 3 cm or larger were found in 58% vs 55% of patients. The proportion classified as AUA high-risk was 58% vs 53%. Adjuvant intravesical therapy was distributed identically across arms: BCG in 58% vs 55% and mitomycin-C in 30% vs 32%.
Investigators concluded that two doses of preoperative mitomycin-C was associated with significantly improved RFS relative to TURBT alone, and noted that the complete absence of progression events in the interventional arm, while observed, should be interpreted with caution given the small sample size and the low number of events.
“Future prospective multicenter phase 3 validation is warranted,” Seo concluded.
Disclosures: Seo disclosed advisory role, consultancy, speaker activity for MSD, Roche, Ono-BMS, Janssen, and Olympus; and research funding from MSD, Roche, Ono-BMS, Astellas, AstraZeneca, and Janssen.
