Trimodality Therapy Shows Promise in Bladder Cancer After BCG Failure

Key Insights

• A phase II study evaluated trimodality therapy as an alternative to cystectomy in bladder cancer patients who had failed BCG treatment.
• The study met its primary endpoint, demonstrating an 88% freedom from cystectomy rate at 3 years with trimodality therapy.
• Overall survival rates at 3 and 5 years were 69% and 56%, respectively, suggesting a potential survival benefit with this approach.

A phase II study suggests that trimodality therapy may offer a bladder-preserving alternative to radical cystectomy for select patients with recurrent T1 urothelial carcinoma of the bladder following Bacillus Calmette-Guerin (BCG) failure. The research, presented at a recent medical conference, highlights the potential of this approach in a challenging patient population where treatment options are limited.

The single-arm study, led by Dahl et al., enrolled 37 patients between 2009 and 2023 with a median age of 74 years. The trimodality therapy consisted of maximal transurethral resection of bladder tumor (TURBT) followed by conventional radiation therapy to the bladder, delivering 61.2 Gy in 34 fractions (over approximately 7 weeks), combined with radiosensitizing chemotherapy using either cisplatin or fluorouracil with mitomycin.

The primary endpoint of the study was the 3-year freedom from cystectomy rate, which reached 88.0%. Key secondary endpoints included overall survival at 3 and 5 years, reported as 69.0% and 56%, respectively. Distant metastasis rates at 3 and 5 years were 12% and 19%, respectively, with 8 patients ultimately succumbing to distant disease.

While the study demonstrates promising efficacy, it's important to note the observed toxicities. Eighteen patients in the evaluable study population experienced grade 3 or higher adverse events, predominantly hematological in nature. Other toxicities included gastrointestinal events, urinary tract infections, hematuria, and metabolic/nutritional events. No unexpected toxicities were reported.

According to National Comprehensive Cancer Network guidelines, radical cystectomy remains the preferred treatment for BCG-unresponsive or BCG-intolerant patients with American Urological Association high-risk group non-muscle invasive bladder cancer. Alternatives such as intravesicular chemotherapy, pembrolizumab, nadofaragene firadenovec, and nogapendekin alfa inbakicept with BCG are available for select patients.

"It would be interesting to further investigate the concept of bladder preservation using modern radiation techniques and novel chemotherapy-sparing radiation-sensitizing agents," noted Nataliya Mar, MD, associate clinical professor at the University of California Irvine Health.