The role of perioperative chemotherapy associated with radical cystectomy (RC) for muscle-invasive bladder cancer has been analyzed in several landmark randomized controlled trials (RCTs) over the past decades. With regard to neoadjuvant chemotherapy (NAC), a meta-analysis of level 1 evidence and long-term results from the largest RCTs support its use, which is currently advocated as the standard of care by most of the clinical guidelines worldwide. However, with regard to the delivery of adjuvant chemotherapy (AC), evidence is more contentious. Specifically, several meta-analyses demonstrated a survival benefit associated with the use of cisplatin-based regimen but investigators identified multiple methodological limitations in most of included RCTs. Nonetheless, AC is currently considered for fit patients with adverse pathological features at RC. It is noteworthy that the delivery of such cytotoxic treatment after surgery may maintain significant anti-tumor activity even in those patients who previously received NAC. Finally, given its greater response rate, the methotrexate, vinblastine, adriamycin plus cisplatin combination remains preferentially considered in the neoadjuvant setting, while the gemcitabine plus cisplatin combination is more commonly delivered in the adjuvant setting because of its better toxicity profile. However, no prospective evidence comparing efficacy of both regimens for NAC or AC is currently available.
