Hypofractionated radiotherapy in the management of bladder cancer

Abstract

Purpose

Trimodal therapy, combining transurethral resection of the bladder tumour, radiotherapy, and concurrent radiosensitization, is an established bladder-preserving alternative to radical cystectomy in muscle-invasive bladder cancer. Hypofractionated radiotherapy has gained interest due to radiobiological advantages and logistical convenience, yet its efficacy and safety remain under evaluation.

Methods

A review of prospective phase II and III trials published between 2000 and 2025 was conducted in Medline using the search engine PubMed. Studies were included if they assessed hypofractionated radiotherapy (excluding stereotactic body radiotherapy) for non-metastatic muscle-invasive bladder cancer within a curative-intent using a trimodal therapy approach. Key endpoints included progression-free survival, overall survival, and toxicity.

Results

Seven prospective trials (five phase II, two phase III) were identified. The largest evidence come from the BC2001 and BCON trials, which demonstrated that a dose of 55 Gy delivered in 20 fractions was non-inferior to a dose of 64 Gy delivered in 32 fractions in terms of locoregional control and overall survival, with similar genitourinary and gastrointestinal toxicity rates. Additional studies confirmed comparable efficacy between hypofractionated and conventional fractionated radiotherapy regimens. Various concurrent systemic therapies were used, including cisplatin, 5-fluorouracil with mitomycin C, gemcitabine, and carbogen with nicotinamide, though no regimen showed clear superiority. Elective pelvic nodes irradiation remains controversial; one phase III trial showed no benefit, while recent data suggest a potential survival advantage without increased toxicity, even in hypofractionated protocols.

Conclusion

Hypofractionated chemoradiotherapy is a safe and effective bladder-preserving strategy in selected patients with muscle-invasive bladder cancer. It offers comparable oncological outcomes and toxicity to conventional radiotherapy, with improved treatment efficiency. While systemic radiosensitization remains essential, further research is needed to optimize agents and clarify the role of pelvic nodes irradiation in hypofractionated settings.