Radiotherapy for High-Risk Non-Muscle-Invasive Bladder Cancer: Current Evidence and Future Directions

Introduction: Non-muscle-invasive bladder cancer (NMIBC) represents approximately 78% of newly diagnosed bladder cancers and is characterized by high recurrence rates and variable progression risk. While transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains standard management, optimal treatment of high-risk and Bacillus Calmette-Guerin (BCG)-unresponsive disease remains controversial. Radiotherapy (RT), particularly in combination with chemotherapy, has been explored as a bladder-preserving alternative. Material and Methods: We conducted a narrative review of published literature evaluating the role of definitive RT in high-risk NMIBC, with emphasis on T1 disease. Retrospective series, prospective trials, meta-analyses, and contemporary guideline recommendations were examined. For each included study, we extracted data on the extent of TURBT (maximal vs. incomplete/non-specified), use and type of concurrent chemotherapy, radiotherapy technique (3D-conformal, IMRT, or proton), treatment volume (bladder only vs. whole pelvis), and dose/fractionation schedule. Results: Early studies evaluating RT alone demonstrated modest complete response rates. More recent approaches incorporating maximal TURBT followed by concurrent chemoradiotherapy report improved outcomes, with complete response rates of approximately 80-88% and 5-year overall survival comparable to surgical series. The phase II NRG/RTOG 0926 trial in recurrent high-risk T1 disease after intravesical therapy failure demonstrated an 81% complete response rate and favorable bladder preservation outcomes. Meta-analytic data suggest 5-year recurrence-free survival around 54% and overall survival near 70%, although evidence remains limited and largely non-randomized. Advances in image-guided and hypofractionated RT may further improve therapeutic outcomes while limiting toxicity. Conclusions: while definitive chemoradiotherapy is a promising option for selected patients, it remains investigational and should be considered only in those who are unfit for or decline radical cystectomy. Prospective randomized studies are needed to better define its role in contemporary management.