Neoadjuvant Chemotherapy Before Radical Cystectomy: Why We Must Adhere?

Aim: To provide a critical literature review on state of the art and novel strategies in the field of neoadjuvant treatments for muscle-invasive bladder cancer (MIBC). Methods: a nonsystematic literature review was performed using PubMed, Scopus and Clinical Trials.gov to retrieve papers related to neoadjuvant treatments for MIBC over the past 15 years. Prospective and retrospective studies were included. Results: Platinum-based treatment is the gold standard and mainly consists of a combination of Cisplatin with Vinblastine, Methotrexate, Doxorubicin, Gemcitabine, Adriamycin or even Epirubicin. The 5-year absolute overall survival benefit of MVAC is 5% and the absolute disease-free survival improves by 9%. CMV treatment is associated with a 10-year overall survival improving from 30% to 36% and a 16% reduction in mortality. Gemcitabine and cisplatin regimen provides complete response in 20% of cases, with non-inferior oncological outcomes compared to MVAC regimen. Recent prospective trials investigating neoadjuvant immunotherapy show high rate of complete response, from 29% with atezolizumab to 39.5% with pembrolizumab. The tyrosine kinase inhibitor pathway is being explored and could offer an interesting strategy to improve survival outcomes. Conclusions: Available evidence suggest better oncological outcomes for MIBC patients receiving neoadjuvant treatment before radical cystectomy. While MVAC remains the standard of care in cisplatin eligible patients, novel strategies are under development for cisplatin ineligible patients whereby immunotherapy seems to hold great promise.