Background and Objectives: Pathological upstaging from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) at radical cystectomy (RC) compromises preoperative risk stratification and may deprive patients of the survival benefit conferred by neoadjuvant chemotherapy. This study aimed to define the frequency and independent predictors of pathological upstaging in a contemporary single-institution cohort, and to characterise its impact on recurrence-free, disease-specific, and overall survival. Materials and Methods: We conducted a retrospective review of a prospectively maintained database of all patients who underwent RC and pelvic lymphadenectomy for urothelial bladder cancer at our institution between January 2009 and December 2023. Upstaging was defined as the final pathological stage ≥ pT2 or pN+ from a clinical stage of <T2N0M0. Clinicopathological factors were evaluated for their association with upstaging using chi-squared, Fisher’s exact, and logistic regression analyses. Survival outcomes—recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS)—were estimated by the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox proportional hazards regression identified independent prognostic factors. Results: Of 1002 patients who underwent RC during the study period, complete clinicopathological data were available for 826. Primary clinical stage at presentation was MIBC (≥T2) in 448 (54.2%) and NMIBC (<T2) in 378 (45.8%). Among NMIBC patients, 102 (27.0%) were upstaged to MIBC at final pathology. Multivariable logistic regression identified concomitant carcinoma in situ (CIS) (p = 0.042), variant histology—predominantly squamous differentiation (p = 0.003)—and urethral involvement (p = 0.003) as independent predictors of upstaging. Upstaged patients had significantly worse 5-year RFS (p < 0.001), DSS (p = 0.01), and OS (p < 0.001) compared with patients who remained NMIBC. No statistically significant difference in survival was observed between patients upstaged at RC and those presenting with primary MIBC. Conclusions: Pathological upstaging occurs in more than a quarter of patients undergoing RC for NMIBC and confers a survival penalty equivalent to that of primary MIBC. Concomitant CIS, variant histology, and urethral involvement identify those at highest risk. These patients warrant aggressive preoperative counselling, expedited surgical planning, and consideration of perioperative systemic therapy.

Background: Female patients undergoing radical cystectomy (RC) for bladder cancer have historically presented with more advanced disease and poorer survival outcomes than males. These disparities have been attributed to biological differences, delayed diagnosis, and variations in treatment delivery. Recent data suggest, however, that outcomes may converge when patients are managed in standardized, multidisciplinary, high-volume centers. This study evaluated the influence of gender on perioperative features and oncological outcomes such as disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) at a tertiary uro-oncology center. Methods: We retrospectively reviewed a prospectively maintained database of patients who underwent open or robotic-assisted RC for histologically confirmed urothelial carcinoma between 2014 and 2023 at Guy’s and St. Thomas’ NHS Foundation Trust. Demographic, perioperative, and pathological variables were stratified by gender to assess their association with DFS, DSS, and OS. Results: A total of 887 patients were included: 640 men (72.2%) and 247 women (27.8%), with similar mean age (68.5 vs. 68.1 years) and tumour histology (pure urothelial carcinoma 85% vs. 83%). Men had a higher prevalence of diabetes and chronic kidney disease, but no significant differences were observed in time from referral to surgery (0.93 vs. 1.03 months, p = 0.93), use of neoadjuvant therapy (21.6% vs. 17.3%, p = 0.25), or surgical approach (p = 0.55). Pathological stage distribution was comparable between sexes (pT0–1: 44% vs. 50%; pT2–4: 56% vs. 50%; p = 0.13). Kaplan–Meier analysis revealed no significant gender-related differences in 12-month DFS (77.3% vs. 75.4%, p = 0.20), DSS (85.6% vs. 86.9%, p = 0.56), or OS (81.2% vs. 85.2%, p = 0.70). Conclusion: In this high-volume tertiary center, gender did not independently influence perioperative or survival outcomes following radical cystectomy. These findings suggest that standardized, multidisciplinary management within specialized bladder cancer pathways may mitigate the pathological and survival disparities historically associated with gender.