Introduction: Early-stage bladder cancer (BCa) has an excellent 5-year survival rates; however, outcomes decline sharply with disease progression. Established risk factors for BCa include tobacco exposure and certain occupational hazards. The objective of this study is to evaluate the feasibility and practicality of conducting a large-scale BCa screening study targeting individuals at elevated risk. Methods and Analysis: This is a prospective, multicenter, observational feasibility study conducted at Cedars-Sinai Medical Center—one of the largest hospital systems in Southern California—and the VA Long Beach Healthcare System. Between April 2022 and January 2025, 200 individuals at risk for developing BCa were enrolled. The primary endpoint is to assess the feasibility of recruiting and retaining 200 participants for longitudinal follow-up over four years. Participants undergo annual evaluations, including collection of demographics, clinical, and exposure data, as well as urine-based molecular analyses. These data will be incorporated into multivariate model to identify predictors of BCa development. Ethics and Dissemination: Given the rising incidence and mortality associated with BCa, early detection—when the disease remains highly treatable—is critical. The use of robust, non-invasive diagnostic tools in high-risk populations provides a promising strategy toward this goal. Although modest in scale, this study represents the first known effort to leverage lung cancer screening clinics as a platform for identifying individuals at risk for BCa, and the first to apply a multiplex immunoassay within this cohort. Findings from this feasibility study will inform optimal strategies for recruitment, retention, and molecular screening in future large-scale, definitive trials. Strengthens and Limitations: (1) This study is the first prospective feasibility trial to evaluate a multiplex urinary immunoassay for BCa screening within a high-risk population recruited from lung cancer screening clinics, leveraging an existing infrastructure to improve recruitment efficiency; (2) The multicenter, observational design with standardized data collection, centralized laboratory testing, and longitudinal urine sampling enhances methodological rigor and reproducibility; (3) Broad inclusion criteria and consecutive recruitment were used to minimize selection bias and reflect real-world high-risk populations; (4) As a feasibility study, the sample size and event rate are not powered to assess definitive diagnostic accuracy or clinical outcomes; (5) Reliance on self-reported exposure data (e.g., tobacco and occupational history) introduces potential information bias despite standardized questionnaires and trained coordinators.
Luu et al. (Thu,) studied this question.