Perioperative chemotherapy and immunotherapy to optimize cystectomy outcomes in the curative intent of non-metastatic muscle-invasive bladder cancer: A systematic review and meta-analysis.

Introduction: Perioperative systemic treatments play a crucial role in the comprehensive management of muscle-invasive bladder cancer. While neoadjuvant platinum-based chemotherapy has a proven efficacy, administering adjuvant chemotherapy can be challenging in patients with multiple comorbidities. Although immunotherapy has shown success in metastatic settings, its effectiveness in both neoadjuvant and adjuvant settings remains under investigation. This study aims to conduct a systematic literature review and meta-analysis to assess the impact of chemotherapy and/or immunotherapy in neoadjuvant and/or adjuvant settings.

Methods: A systematic review and meta-analysis were conducted by consulting the PubMed, Scopus, and ClinicalTrial.gov databases for the period from 1994 to 2023. The analysis utilized Forest Plots for key points of interest: overall survival/pathologic response for neoadjuvant chemotherapy (NAC) and overall survival/disease-free survival for adjuvant chemotherapy (AC), employing random or fixed models.

Results: The systematic review included 26 articles, and 14 were incorporated into the meta-analysis. For NAC, five studies assessed overall survival, yielding an overall hazard ratio (HR) of 0.84 [0.75-0.94]; P=0.002. Pathologic response under NAC was evaluated in five studies, resulting in an overall odds ratio (OR) of 0.3 [0.2-0.4]; P<0.001 compared to cystectomy and 0.86 [0.65-1.13]; P=0.28 for MVAC vs. GC. Regarding AC, six studies investigated overall survival, revealing an overall HR of 0.93 [0.77-1.12]; P=0.46. Disease-free survival under AC was examined in seven studies, with an overall OR of 0.58 [0.44-0.78]; P<0.001. Meta-analysis was not conducted for immunotherapy due to limited phase II studies in the neoadjuvant setting and only two available studies in the adjuvant setting.

Conclusion: This study reaffirms the efficacy of platinum-based chemotherapy in neoadjuvant and adjuvant scenarios, enhancing overall survival in muscle-invasive bladder cancer patients. Immunotherapy exhibits promising outcomes in tumor downstaging in the neoadjuvant setting and in disease-free survival, in the adjuvant setting.