INTRODUCTION/BACKGROUND: A recent study reported that patients with residual urothelial carcinoma of the bladder subsequent to neoadjuvant/induction chemotherapy (NAIC) prior to RC exhibited inferior oncological outcomes in comparison to pathological stage-matched patients who underwent upfront RC. Our hypothesis is that this may be ascribed to variations in preoperative CT-stage rather than the impact of chemotherapy. PATIENTS AND METHODS: This retrospective multicentre study included 513 patients who underwent RC for cT2-4N0-3M0 disease between 2010 and 2017. Patients were categorized based on pathological outcomes: pathological complete response (pCR, (y)pT0N0), complete downstaging (pCD, (y)pT0/is/a/1N0) and residual muscle-invasive and/or node positive disease (rMIBC, (y)pT2-4N0 and/or (y)pN1-3). RESULTS: Of the total cohort, 175 (34.1%) patients underwent NAIC+RC, while 338 (65.9%) underwent upfront RC. NAIC+RC patients exhibited lower age and CCI-scores, along with higher cT&N-stage (all P-values <
.001). The mOS was 60.5 months for NAIC+RC and 49.4 months for upfront RC (P-value = .171). In patients with rMIBC, survival was inferior after NAIC+RC compared to upfront RC. However, the clinical stage distribution between NAIC+RC and upfront RC was imbalanced, with 3% versus 49% cT2N0 patients and 47% versus 9% cT4b and/or N+ patients, respectively. Following adjustments for cT & N-stage, age, and CCI-scores in multivariable Cox proportional-hazards analysis, worse OS was associated with upfront RC (HR 1.52, [95% CI, 1.11-2.10], P-value = .009). CONCLUSION: The observed inferior survival in cT2-4N0-3M0 patients with rMIBC after NAIC+RC compared to those undergoing upfront RC resulted from worse preoperative characteristics, including clinical stage. The representation of clinical disease stage should not be overlooked in survival analyses.