A new subtyping model for residual invasive disease after cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer

Muscle invasive bladder cancer (MIBC) is an aggressive malignancy and half of the patients develop metastatic disease within 2 years, which is generally incurable and leads to early mortality (1). Based on prospective randomized trials, MIBC is treated with cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) (2-4). However, when examining the SWOG8710 trial that evaluated optimal MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) NAC, the 5-year overall survival (OS) exhibited a modest absolute increment from 42% to 57% with RC alone to NAC followed by RC. Those without pathologic complete remissions (> pT0) demonstrated poor outcomes with a median survival of 3.7 years, while those with pT0 disease at RC exhibited essentially a normal life expectancy (5). Hence, it is critical to understand the drivers of resistance in those with > pT0 disease following NAC in order to make further advances in these patients