Intravesical chemotherapy combination treatments for BCG-unresponsive nonmuscle invasive bladder cancer

There is an increasing interest in developing bladder sparing therapies (BSTs) for patients with Bacillus Calmette-Guérin unresponsive (U-BCG) nonmuscle invasive bladder cancer (NMIBC) as an alternative to radical cystectomy (RC). We aimed to perform a review of efficacy and safety of intravesical chemotherapy combination treatments for U-BCG NMIBC patients according to the most recent evidence.

The use of intravesical chemotherapy combination treatments for U-BCG patients has shown promising efficacy and tolerability especially in retrospective series. For U-BCG patients, the most used option in this context is intravesical gemcitabine plus docetaxel, with a 2-year recurrence free-survival ranging between 37-62%, and a 2-year progression free-survival rate of 70-95%, with grade 3-5 adverse events (AEs) varying between 3-8% according to the most recent reports. Other studies are investigating the combination of more than two chemotherapy agents, with a recent prospective trial showing encouraging results for the combination of three intravesical drugs (gemcitabine, cabazitaxel, cisplatin) with a cystectomy-free survival rate of 97% at 1-year and no evidence of grade 3-5 AEs at a median follow-up of 20 months.

Recent evidence on intravesical chemotherapy combination treatment for U-BCG NMIBC is mostly based on retrospective studies, especially those investigating gemcitabine/docetaxel. However, some studies are currently investigating the combination of more than two chemotherapy agents. Overall, studies show good short-term efficacy, acceptable rates of disease progression, and tolerability in patients with U-BCG NMIBC. Nevertheless, prospective studies will be needed to support the widespread use of new BSTs as valid alternatives to RC in patients who failed BCG.