Expect the Unexpected: Frequency, Predictors, and Survival Impact of Pathological Upstaging from Non-Muscle-Invasive to Muscle-Invasive Bladder Cancer Following Radical Cystectomy.

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.