Role of neoadjuvant intravesical mitomycin C (MMC) treatment in patients with recurrent non-muscle invasive bladder cancer (NMIBC): A randomized controlled trial.

A single immediate post-TURBT instillation of intravesical MMC is well tolerated and reduces the recurrence risk to 25%-38% in patients with NMIBC by eliminating residual viable tumour cells or preventing any free-floating cancer cells during and after TURBT from reseeding2,3,4. However, the administration of intravesical MMC within 24 hours of TURBT is associated with more extensive MMC-induced trans mural necrosis/ulceration in an area of thinned muscularis propria at the base of the deep resection than the usual muscle necrosis observed after TURBT alone, resulting in secondary perforation5. Various studies have defined different intravesical MMC schedules, but definite instillation intervals and numbers in the neoadjuvant setting are yet to be defined. A recent randomized phase 2 study aiming to assess the efficacy and safety of neoadjuvant intravesical mitomycin-C in patients with NMIBC suggested that two doses of neoadjuvant intravesical mitomycin-C are safe and effective in reducing NMIBC recurrence and progression after TURBT6. Although MMC has been used in neoadjuvant settings via several administration schedules, the dose and schedule of intravesical chemotherapy for reducing the recurrence risk of NMIBC remain unknown. Another RCT noted that intravesical electromotive drug administration  (EMDA) mitomycin before TURBT is feasible and safe whilst also reducing recurrence rates and enhancing the disease-free interval when compared with intravesical passive diffusion (PD) mitomycin after TURBT and TURBT alone7. A randomized phase 2 clinical study assessing, the efficacy of a short-term intensive schedule of neoadjuvant intravesical chemotherapy in patients with recurrent NMIBC, reported that the intensive short-term schedule of neoadjuvant chemotherapy is safe and without additional toxicity when compared with the weekly regimen8. The DaBlaCa-13 Study reported that short-term, intensive chemo resection yields a tumour response of 57%, resulting in only half of those treated with chemo resection needing a TURBT, while also suggesting it has lesser clinical side effects9.

Here, we compared the feasibility and potential efficacy of 2 different regimens of intravesical MMC (IMMC) prior to TURBT, in patients with recurrent NMIBC, followed by an adjuvant instillation following the surgery.