Risk Factors and Prediction Modeling for Multiple Recurrences of Non-Muscle Invasive Bladder Cancer

Project Summary / Abstract Bladder cancer (BCa) is the sixth most diagnosed cancer in the US, and the 10th ranked cancer in the world posing a significant disease burden worldwide. The well-established risk factors for BCa are increasing age, male sex, race/ethnicity, cigarette smoking, obesity, and several environmental and occupational exposures. Of the estimated 600,000 newly diagnosed BCa cases each year worldwide, 70% to 75% are non-muscle- invasive bladder cancers (NMIBC), a genetically and clinically distinct entity from muscle invasive tumors. Although NMIBC have an excellent five-year survival rate (>95%), their recurrence rates are remarkably high (40%-70%), leading to repeated treatments and follow-up clinic visits of patients with substantial healthcare costs. Several clinical studies have examined associations of clinical and pathological features of NMIBC with risk of recurrence, but results have been inconsistent. To-date little is known about epidemiological and clinical risk factors for multiple recurrences of NMIBC. The aims of the proposed study are: i) to examine the associations of demographic, lifestyle and social factors, tumor characteristics (e.g. stage, grade, tumor size), comorbidities and cancer treatments with risks of first and multiple (e.g. 2, ≥3) NMIBC recurrences and ii) to develop and validate risk prediction models for multiple recurrences. The goal is to better understand the contribution of various epidemiological, lifestyle, and clinical risk factors that could be used to identify which NMIBC patients are at the highest risk for multiple recurrences. We will use existing demographic, lifestyle, social, clinical and tumor pathology data, cancer treatments and recurrence events collected from two large cohorts of NMIBC patients: the Be-Well Study (N=1,472) within the Kaiser Permanente healthcare system in California, US, and the BladderBaSe cohort of 38,547 patients from Sweden. About 30% to 40% of patients have experienced multiple recurrences of NMIBC in each cohort. Additional outcome events will be accrued with extended follow-up of both cohorts through 12/31/2024. Results of this study will provide important new insights on the associations of various epidemiological and lifestyle risk factors, clinical and tumor pathological data with risk of multiple recurrence of NMIBC in different populations. This is a clinical research priority and an important next step in the development of individualized patients care, targeted surveillance and clinical management of patients with NMIBC.