Recent developments in perioperative combination therapy in muscle-invasive bladder cancer

Abstract

Purpose of reviewA summary of recent literature to provide a comprehensive overview of the current state of systemic perioperative treatment combinations for muscle-invasive bladder cancer (MIBC).Recent findingsWe discuss recent developments in standard and experimental treatment modalities. The VESPER trial has shown that six cycles of neoadjuvant dose-dense MVAC are superior to four cycles of gemcitabine/cisplatin (GC), though it is unclear whether the superiority is derived from the specific regimen or number of cycles. Adjuvant cisplatin-based chemotherapy, a subject of longstanding debate, was shown to have comparable overall survival-benefit to neoadjuvant chemotherapy in an updated meta-analysis. Neoadjuvant chemotherapy and anti-PD-(L)1 show encouraging results, but with no comparative studies to standard care, context is lacking. Immunotherapeutic neoadjuvant anti-CTLA-4/PD-(L)1 combinations or combinations of checkpoint inhibitors with antibody-drug-conjugates are in early stages of development and show promising preliminary results.SummarySix cycles of neoadjuvant dose-dense MVAC are superior to four cycles of gemcitabine/cisplatin. Adjuvant cisplatin-based chemotherapy is a viable option for patients with high-risk tumours who did not receive prior neoadjuvant treatment. The added value of anti-PD-(L)1 to chemotherapy still needs to be established. Novel developments in immunotherapy combinations, while promising, are still in an early stage and randomized studies are ongoing.

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

“…For example, individual variations in drug responses [1], differences among populations [2], different drug formulations [3], single or multiple drug administration [4] and different routes of drug administration [5] all have different effects on treatments. Similarly, the need for optimal, target-specific therapies including drug combinations as well as other parameters will also effect overall treatments [6][7][8][9][10]. The risk/benefit assessment of drug posology selection and effective use is a continuous developmental process even after drug registration and during post-marketing surveillance [11][12][13][14][15].…”