Pathological downstaging following radical cystectomy for muscle-invasive bladder cancer: Survival outcomes in the setting of neoadjuvant chemotherapy versus transurethral resection only

Introduction: Neoadjuvant chemotherapy (NAC) improves survival for patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC). The overall survival (OS) advantage with NAC is primarily seen in patients who achieve pathological downstaging. However, a substantial number of patients achieve pathological downstaging following transurethral resection (TUR) without NAC. Objectives: To analyze the OS outcomes in patients who achieve pathological downstaging in the setting of NAC vs. TUR only. Materials and Methods: We reviewed the National Cancer Database (NCDB) for patients diagnosed with MIBC who underwent radical cystectomy between 2004 and 2014. Patients who achieved complete downstaging (CD) (pT0N0) or noninvasive downstaging (NID) (pT0/Tis/TaN0) were further analyzed. OS was evaluated by comparing those who underwent NAC to those who underwent TUR only. Results: A total of 24,763 patients with MIBC were identified. 1,781 (7.2%) patients had NID and 1,015 (4.1%) had CD. Of all patients, 3,838 (15.5%) underwent NAC. In patients with NID, 757 (42.5%) underwent NAC and 1024 (57.5%) had cystectomy after TUR only. In patients with CD, 465 (45.8%) had NAC, while 550 (54.2%) had TUR only. In both NID and CD, cT2 patients were more likely to have TUR only (P = 0.019, P < 0.001), cT3 patients were more likely to receive NAC (P = 0.008, P < 0.001). Compared to the TUR only group, NAC was associated with improved 5-year OS in those with NID, 77% compared to 68% (HR 0.68, 95% CI [0.52–0.90]), as well as those with CD, 80% vs. 70% (HR 0.59, 95% CI [0.39–0.89]). Conclusions: NAC was associated with significant overall survival benefit in the subset of patients who achieved CD and NID at radical cystectomy. Overall, NAC was underutilized in patients with MIBC.