Radiation Therapy in the Management of Muscle-invasive Bladder Cancer with Carcinoma in Situ: Still a No Go?

Background and objective: This narrative review explores the impact of carcinoma in situ (CIS) on outcomes in muscle-invasive bladder cancer (MIBC) after trimodal therapy (TMT) comprising transurethral resection of bladder tumor, a radiosensitizing agent and radiation therapy (RT). There is limited and inconsistent evidence on the effect of CIS, often considered a contraindication to TMT, on treatment efficacy.

Methods: We reviewed studies evaluating the influence of TMT and RT alone on clinical outcomes in CIS-associated MIBC. Endpoints evaluated included complete response (CR) rates, overall survival (OS), disease-specific survival (DSS), and RT protocol variations, such as fractionation schedules, total doses, and the use of image-guided RT.

Key findings and limitations: Evidence from studies on RT alone is inconsistent, often because of outdated regimens and inadequate CIS evaluation. Retrospective TMT studies suggest that CIS does not significantly affect CR rates, although its impact on OS and DSS remains uncertain, particularly with suboptimal RT protocols. Emerging evidence supports continuous and moderately hypofractionated RT combined with image-guided RT as potential strategies to improve outcomes. Standardized definitions of extensive CIS and better patient selection are critical for optimizing bladder preservation strategies.

Conclusions and clinical implications: CIS presents significant challenges for TMT in MIBC, necessitating precise assessment, advanced RT techniques, and multidisciplinary collaboration. Novel therapies, including immunotherapy and intravesical agents, may further improve outcomes. Research into standardized protocols is essential to optimize treatment strategies.