Does perioperative systemic therapy represent the optimal therapeutic paradigm in organ-confined, muscle-invasive urothelial carcinoma?

Although urothelial carcinoma can occur in any part of the urinary tract, 90–95% of urothelial malignancies arise in the bladder [1]. Conversely, approximately 90% of bladder malignancies have a urothelial origin [2]. According to GLOBOCAN, approximately 570,000 individuals were diagnosed with bladder cancer (BCa) in 2020 worldwide, with approximately 210,000 dying of the disease [3]. Southern Europe is the world area presenting with the highest incidence of BCa in males [2], with peaks of over 70 cases per 100,000 males in certain areas of southern Italy [4]. Cystectomy [5] and radical nephroureterectomy [6] represent the mainstay of treatment of localized urothelial cancer that is not amenable to conservative treatment such as intravescical BCG [7]. While both chemotherapy based on platinum agents and immune therapy based on anti PD-1/PDL-1 agents (programmed death-1/programmed death ligand-1) such as pembrolizumab and avelumab have been definitively proven to extend survival in patients with advanced/metastatic disease [8–10], their effect in terms of survival prolongation in the perioperative setting requires to be better investigated. In a meta-analysis [11] assessing overall survival in 2890 BCa patients who received neoadjuvant platinum-based chemotherapy followed by radical cystectomy and 10,418 BCa patients who underwent radical cystectomy alone, neoadjuvant chemotherapy was associated with a 18% reduction of the risk of death with a hazard radio (HR) of 0.82 (95% CI: 0.71–0.95; p = 0.009).