Contemporary best practice in the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer

Abstract

Background: We aimed to provide a comprehensive literature review on the best practice management of patients with nonmetastatic muscle-invasive bladder cancer (MIBC) using neoadjuvant chemotherapy (NAC). Method: Between July and September 2018, we conducted a systematic review using MEDLINE and EMBASE electronic bibliographic databases. The search strategy included the following terms: Neoadjuvant Therapy and Urinary Bladder Neoplasms. Results: There is no benefit of a single-agent platinum-based chemotherapy. Platinum-based NAC is the gold standard therapy and mainly consists of a combination of cisplatin, vinblastine, methotrexate, doxorubicin, gemcitabine or even epirubicin (MVAC). At 5 years, the absolute overall survival benefit of MVAC was 5% and the absolute disease-free survival was improved by 9%. This effect was observed independently of the type of local treatment and did not vary between subgroups of patients. Moreover, a ypT0 stage (complete pathological response) after radical cystectomy was a surrogate marker for improved oncological outcomes. High-density MVAC has been shown to decrease toxicity (with a grade 3–4 toxicity ranging from 0% to 26%) without impacting oncological outcomes. To date, there is no role for carboplatin administration in the neoadjuvant setting in patients that are unfit for cisplatin-based NAC administration. So far, there is no published trial evaluating the role of immunotherapy in a neoadjuvant setting, but many promising studies are ongoing. Conclusion: There is a strong level of evidence supporting the clinical use of a high-dose-intensity combination of methotrexate, vinblastine, doxorubicin and cisplatin in a neoadjuvant setting. The landscape of MIBC therapies should evolve in the near future with emerging immunotherapies.