DNA repair capacity and tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC).

Abstract

305 Background: NMIBC requires lifelong surveillance to monitor for recurrence. Identifying patients at greatest risk and altering surveillance accordingly could impact health care cost. Inadequate DNA repair may increase the risk for developing subsequent tumors. This prospective study evaluated the association between DNA damage/repair capacity and tumor recurrence with the goal of finding new prognostic markers. Methods: Patients newly diagnosed with NMIBC (n=100) who received standard care provided blood samples and completed risk surveys and were followed for a median of 78 mos. DNA damage in peripheral blood lymphocytes measured with the Comet Assay revealed constitutive damage, sensitivity to carcinogens after exposing cells to the tobacco-derived carcinogen BPDE, and repair capacity after allowing cells to repair post BPDE induced damage. DNA damage was expressed as log-transformed Tail Intensity. Median time to recurrence and cumulative incidence of recurrence at 4 mos were estimated by Kaplan-Meier methods and compared by log-rank test. Hazard ratios for recurrence in association with patient characteristics and DNA damage/repair variables were estimated with Cox proportional hazard models. Associations of DNA damage/repair variables between patients’ characteristics were tested with Wilcoxon Rank-Sum. Results: This NMIBC cohort included patients with mean age 64 yrs and 71% males. Tumors were high grade in 74% and multifocal in 34%. Median time to recurrence was 6 months and 42/69 recurrences occurred <4 mos. Patients with higher grade/stage, multifocality, and intravesical therapy had higher cumulative incidence of recurrence at 4 mos (p<0.01). Those with higher stage/grade compared to low stage/grade tumors showed significant reduction in DNA repair capacity after exposure to BPDE (p<0.03). Conclusions: In univariate analysis, DNA damage is associated with higher stage and higher grade tumors; however host DNA damage/repair capacity does not predict recurrence in NMIBC. Traditional disease characteristics including multifocality, high-grade, increasing stage, and intravesical therapy remained predictors of recurrence.