Bladder-Sparing Chemoradiotherapy Combined with Immune Checkpoint Inhibition for Locally Advanced Urothelial Bladder Cancer—A Review

SIMPLE SUMMARY: Immunotherapy with immune checkpoint inhibition (ICI) has provided durable treatment responses in advanced, metastatic, bladder cancer patients. The first trials using checkpoint inhibitors before surgery, when the cancer is still confined to the pelvis, without signs of metastasis, have reported promising results. We reviewed the literature to identify clinical trials combining ICI with bladder-sparing chemoradiotherapy (CRT). Radiotherapy stimulates the immune system, thereby possibly inducing an additive effect in combination with checkpoint inhibition. Currently, twelve trials are treating patients with this immunochemoradiotherapy (iCRT) combination treatment. Several combinations with different chemotherapeutics and ICI added to CRT appear safe and feasible. Further research and comparative trials are needed to prove whether iCRT has additional clinical value for bladder cancer patients. ABSTRACT: Despite current treatment strategies, the 5-year overall survival of muscle-invasive bladder cancer (MIBC) is approximately 50%. Historically, radical cystectomy (RC) with neoadjuvant chemotherapy has been the first-choice treatment for this patient group. Recently, several studies have reported encouraging results of using immune checkpoint inhibitors (ICI) prior to RC. However, in recent years, bladder-sparing alternatives such as CRT have gained popularity. The effect of radiotherapy on the tumor microenvironment is an important rationale for combining CRT with ICI therapy. Worldwide, twelve immunochemoradiotherapy (iCRT) trials are ongoing. Each study employs a different chemotherapy and radiotherapy regimen and varies the timing of ICI administration concurrent to radiotherapy, adjuvant, or both. Five studies have presented (preliminary) results showing promising safety and short-term survival data. The first peer-reviewed publications are expected in the near future. The preclinical evidence and preliminary patient data demonstrate the potential of iCRT bladder-sparing treatment for bladder cancer.