Association Between Symptomatic Versus Asymptomatic Recurrence and Survival in Bladder Cancer

Abstract Background The benefit of surveillance after curative cystectomy in bladder cancer is unproven, but might be justified if detection of asymptomatic recurrence improves survival. Previous studies showing a benefit of surveillance might have been affected by lead-time or length-time bias. Materials and Methods We conducted a retrospective cohort study among 463 cystectomy patients at the University of Pennsylvania. Patients were followed according to a standardized protocol and classified according to asymptomatic or symptomatic recurrence detection. Primary outcome was all-cause mortality. Adjusted Cox regression models were used to assess the effect of mode of recurrence on survival from time of cystectomy (model 1) and time of recurrence (model 2) to account for lead and length time. Results One hundred ninety-seven patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. Relative to patients with asymptomatic recurrence, patients with symptomatic recurrence had significantly increased risk of death (model 1: hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.07-2.61; model 2: HR, 1.74, 95% CI, 1.13-2.69) and had lower 1-year overall survival from time of recurrence (29.37% vs. 55.66%). Symptomatic patients were diagnosed with recurrence a median of 1.7 months before asymptomatic patients, yet their median survival from recurrence was 8.2 months less. Conclusion Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, which cannot be explained by lead- or length-time bias. Similar methods to account for these biases should be considered in studies of cancer surveillance. Shortening surveillance intervals might allow for detection of more recurrences in an asymptomatic phase.