Neoadjuvant instillation without TURBt is reasonable option in patients motivated to avoid invasive procedures

In recent years the management of non-muscle-invasive bladder cancer has undergone radical changes. Intravesical Bacillus Calmette-Guérin (BCG) has long been established as the therapeutic standard when superiority was demonstrated in carcinoma in situ and stage Ta urothelial cancer of the bladder. For decades after the approval of intravesical BCG, no other effective therapies were available for this disease. Valrubicin received FDA approval but had only modest efficacy and was not widely adopted or utilized. Recently, a number of novel therapies have demonstrated efficacy in BCG-failure bladder cancer such as systemic intravenous pembrolizumab, intravesical gemcitabine alternating with docetaxel, and intravesical gene therapy with nadofaragene firadenovec-vncg (Adstiladrin).

Mitomycin is an antitumor antibiotic that inhibits DNA synthesis by producing DNA cross-links that halt cell replication and eventually cause cell death. Intravesical mitomycin has long been used in the treatment of intermediate-risk superficial bladder cancer. The standard regimen involves instillations into the bladder through a catheter weekly for 6 weeks.

A recent study by Lindgren et al. evaluated a neoadjuvant intensive regimen of intravesical mitomycin instilled three times a week for 2 weeks, and compared the outcomes with the standard weekly regimen for 6 weeks. The study was conducted in patients with relapsed/recurrent NMIBC, and the majority of patients (70%) had a history of low-grade disease.

Interestingly, there was no statistically significant difference in recurrence-free survival; however, in the neoadjuvant intensive regimen group 29% of patients were able to avoid invasive procedures such as transurethral resection of bladder tumor (TURBt) as compared with the standard arm of all patients receiving TURBt followed by mitomycin instillation.

The study concludes that avoiding invasive procedures is a goal worthy of achieving in this patient population with a change in the regimen, especially as no safety risk was incurred.

Bladder cancer is a disease of the elderly. The risks of anesthesia and postoperative infections, bleeding, and hospitalizations are magnified in patients of advanced age and multiple comorbidities. The study raises an important management endpoint for clinical trial design: Decreasing the requirement for invasive procedures is an especially important goal in this patient population.

If cancer control is not compromised, then reducing the hassle, cost, and morbidity of invasive procedures is a practically useful endpoint. However, the advancement of technology has resulted in urine-based genomic tests that have reasonable sensitivity and specificity to detect relapse. The cost of these tests is considerable and maybe they would be best applied to the patients with a history of high-grade NMIBC where management would involve consideration of multiple other therapies and the risk of progression to muscle-invasive disease is substantially higher.

In conclusion, the neoadjuvant instillation of intravesical mitomycin without doing TURBt is a reasonable option to consider in patients motivated to avoid invasive procedures but committed to close cystoscopy monitoring and surveillance. Careful selection of patients with a history of low- to intermediate-grade NMIBC, and a minimum treatment-free interval of at least 2 years after intravesical BCG, is required.