Clinical predictors and prognostic significance of pathologic disease upstaging at radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC).

e16601 Background: Imaging and cystoscopy can frequently underestimate disease stage in MIBC. We evaluated clinical and pathological predictors of pathologic disease upstaging (pUS) and its prognostic implications in patients with MIBC treated with RC +/- neoadjuvant chemotherapy (NAC). Methods: We included patients with MIBC (≥cT2, N0-3, M0) who underwent RC between Feb 2004 through Oct 2020. Patients were grouped into those who were upstaged (either T or N stage) at RC with NAC, those who were upstaged without NAC, and those who were not upstaged (reference group). Baseline characteristics were summarized using descriptive statistics. Logistic regression models assessed the association between pUS and baseline characteristics to estimate the odds ratios for being upstaged. Kaplan-Meier method estimated overall survival (OS) and recurrence-free survival (RFS), and log-rank test compared the survival distribution between groups. Univariable and multivariable (MV) Cox regression models identified variables associated with OS and RFS. Results: A total of 281 patients with MIBC were included, of which 39% (n = 111) were upstaged either with (n = 40) or without NAC (n = 71). Most patients were Male (79%), White (73%), had cT2 stage (85%), and had a median age at surgery of 72 yrs. Patients in the pUS with NAC group were more likely to be younger (median age 67.3 yrs) compared to those in the pUS without NAC (75 yrs) or no pUS groups (70 yrs; P < 0.001). Pre-operative hydronephrosis (P = 0.01), elevated pre-operative creatinine (P = 0.02), and clinical N+ (P < 0.001) were more prevalent in the pUS groups (with or without NAC) compared to patients without pUS. The presence of pre-operative hydronephrosis was associated with a significantly higher risk of pUS (77.6% vs. 22.4%) [OR 2.19 (95% CI 1.29–3.71), P= 0.004] after adjusting for covariates such as lymphovascular invasion (LVI) and clinical T stage. On MV analysis, adjusting for covariates such as age, sex, preoperative hydronephrosis, LVI, and T stage, pUS with [HR 1.98 (95% CI 1.24–3.16), P= 0.004] and without NAC [HR 3.20 (95% CI 2.24–4.59), P< 0.001] was associated with significantly worse median OS (30.8 mos and 19.4 mos, respectively) compared to patients without pUS (80.7 mos). Similarly, pUS with [HR 2.43 (95% CI 1.56-3.80), P< 0.001] and without NAC [HR 3.04 (95% CI 2.13-4.34), P< 0.001] also correlated with significantly worse RFS on MV analysis. Conclusions: Preoperative hydronephrosis was the strongest predictor of pUS independent of other baseline covariates. The significantly worse outcomes in the pUS group highlight the need for better pre-operative risk stratification strategies to guide patient selection for multimodal or bladder-preserving strategies.