Effectiveness of Early Radical Cystectomy for High-Risk Non-Muscle Invasive Bladder Cancer

SIMPLE SUMMARY: There is currently contradictory evidence available regarding the use of early radical cystectomy for high-risk non-muscle-invasive bladder cancer that can be performed either upfront or in a delayed setting after BCG failure. Thus, we aimed to compare the perioperative and oncological outcomes between patients who underwent upfront vs. delayed early radical cystectomy. Our results suggest similar perioperative outcomes between the two treatment groups, with an increased risk of pathological upstaging after upfront early radical cystectomy that did not impact survival, as compared to delayed early radical cystectomy. However, further studies are needed to determine whether a subgroup of patients might still benefit from upfront early radical cystectomy, given the highly heterogeneous prognosis of this population. This supports the initial use of intravesical instillations of BCG for patients with high-risk non-muscle-invasive bladder cancer, but further studies are needed to determine if any specific subgroup could still benefit from upfront early radical cystectomy. ABSTRACT: Purpose: The purpose of this study is to compare perioperative and oncological outcomes of upfront vs. delayed early radical cystectomy (eRC) for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Methods: All consecutive HR-NMIBC patients who underwent eRC between 2001 and 2020 were retrospectively included and divided into upfront and delayed groups, according to the receipt or not of BCG. Perioperative outcomes were evaluated and the impact of upfront vs. delayed eRC on pathological upstaging, defined as ≥pT2N0 disease at final pathology, was assessed using multivariable logistic regression. Recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS) were compared between upfront and delayed eRC groups using inverse probability of treatment weighting (IPTW)-adjusted Cox model. Results: Overall, 184 patients received either upfront (n = 87; 47%) or delayed (n = 97; 53%) eRC. No difference was observed in perioperative outcomes between the two treatment groups (all p > 0.05). Pathological upstaging occurred in 55 (30%) patients and upfront eRC was an independent predictor (HR = 2.65; 95% CI = (1.23–5.67); p = 0.012). In the IPTW-adjusted Cox analysis, there was no significant difference between upfront and delayed eRC in terms of RFS (HR = 1.31; 95% CI = (0.72–2.39); p = 0.38), CSS (HR = 1.09; 95% CI = (0.51–2.34); p = 0.82) and OS (HR = 1.19; 95% CI = (0.62–2.78); p = 0.60). Conclusion: our results suggest similar perioperative outcomes between upfront and delayed eRC, with an increased risk of upstaging after upfront eRC that did impact survival, as compared to delayed eRC.