Bladder preservation therapy in muscle-invasive bladder cancer: Current evidence and future perspectives

Abstract

: Radical cystectomy has been widely accepted as the standard treatment in muscle-invasive bladder cancer. However, removal of the bladder requires urinary diversions and substantially impairs patients’ quality of life. Radical cystectomy is also associated with a significant risk of perioperative complications and mortality. Bladder preservation therapy has been explored as a potential alternative to overcome such limitations of radical cystectomy, and a growing body of evidence suggests that bladder preservation therapy could become the primary treatment strategy in muscle-invasive bladder cancer patients. This review aims to provide an overview of the current practices, efficacy, limitations, and future perspectives on bladder preservation therapy. The trimodality protocol of bladder preservation therapy consists of maximal transurethral resection of the bladder tumor followed by radiotherapy with concurrent chemotherapy (chemoradiotherapy). Prospective studies demonstrated that the 5-year overall survival rates are comparable in both bladder preservation therapy and radical cystectomy (50–70%), suggesting that the two treatment paradigms have similar long-term outcomes. Major limitations of bladder preservation therapy include a significant risk of recurrence and insufficient survival outcomes, particularly in chemoradiotherapy non-responders. In addition, prediction of chemoradiotherapy response remains challenging even when clinical manifestations include large tumor size, advanced T stage, multifocality, concomitant carcinoma in situ, and hydronephrosis. Recently, different molecular biomarkers have been identified that could help select optimal muscle-invasive bladder cancer patients for bladder preservation therapy. A personalized treatment plan and further refinements of bladder preservation protocols are expected to improve treatment outcomes. For instance, consolidative partial cystectomy and pelvic lymph node dissection could be used as an adjunct in chemoradiation-based bladder preservation therapy to lower the recurrence rate of muscle-invasive bladder cancer. Additionally, several clinical trials are ongoing to explore whether synergistic anti-tumor activity, achieved by a combination of immune checkpoint inhibitors and chemoradiation-based bladder preservation therapy, could achieve beneficial results in muscle-invasive bladder cancer patients.