Concomitant chemotherapy in trimodal treatment of patients with muscle invasive bladder cancer: A systematic review of prospective trials

Background and objective

For selected patients with muscle-invasive bladder cancer (MIBC), trimodal therapy (TMT) incorporating transurethral resection of the tumor and chemoradiotherapy is an alternative to radical cystectomy. Concurrent chemotherapy (CC) is a pivotal component of TMT, however, the optimal CC protocol remains unknown. This systematic review aims to assess efficacy and safety outcomes of CC protocols used in TMT.

Methods

A systematic literature search in the PubMed and Embase databases was performed to identify eligible studies published between 1980 and March 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Data extraction and risk of bias assessment were performed following predefined criteria.

Key findings and limitations

50 studies met the inclusion criteria. Cisplatin-based CC protocols were the most reported. The highest level of evidence was found for 5-fluorouracil and Mitomycin C and for Carbogen-Nicotinamide. However, significant heterogeneity in patient selection, treatment modalities, follow-up and reported outcomes precluded comparison between trials. Outcomes were similar regardless of CC, with 5-year overall survival around 50 %. Bladder preservation rates ranged from 60 % to 90 %. Distant metastasis rates varied from 10 % to 45 %. Locoregional control rates seemed improved with cisplatin combinations despite an increased acute toxicity. Acute and late toxicity were however relatively low across CC protocols. There was no decrease in gastro-intestinal or urinary Quality of Life. Scarce data were available for elderly patients.

Conclusions and clinical implications

With similar efficacy and toxicity profiles, and in the absence of comparability among trials, our review does not provide sufficient data to determine the optimal CC for TMT of MIBC. TMT is a well-tolerated and efficient approach with tailored strategy available for patients with localized MIBC.