Patient-reported outcomes as non-muscle-invasive bladder cancer clinical trial endpoints

To evaluate the frequency at which patient-reported outcomes (PROs) are incorporated as nonmuscle-invasive bladder cancer (NMIBC) clinical trial endpoints.

Interventional trials limited to patients with NMIBC were queried from clinicaltrials.gov from 1994 to 2025 (start of trial). Observational studies or those without a discrete intervention were excluded. The incorporation of all PROs as primary and secondary endpoints was recorded. PROs were not limited to validated tools. They were defined according to United States Food and Drug Administration (FDA) guidance as any information about a patient's health/experience coming directly from the patient without interpretation by a provider/investigator. Categorical variables were analysed with chi-square and Fisher's exact tests, when applicable, and continuous variables were analysed with the Mann-Whitney U test.

A total of 94 clinical trials were included, of which 21 (22%) incorporated PROs. PROs were included in 3% and 20% of trials as primary and secondary endpoints, respectively. The most commonly used PROs include the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EORTC QLQ-Nonmuscle-Invasive Bladder Cancer 24 module (incorporated in 48% and 43% of NMIBC trials using PROs, respectively). Trials that incorporated PROs as endpoints included higher median anticipated patient enrolments (median [interquartile range] number of patients 166 [461] vs 46 [101], P = 0.002) and were more likely to be randomised controlled trials (62% vs 41%, P = 0.057). There was no difference in funding mechanism (industry-sponsored vs cooperative group/federally funded) between trials that did and did not incorporate PROs. There was little change in PRO incorporation as trial endpoints over time.

Despite recent emphasis from the FDA, patient advocacy groups, and the scientific community on the use of PRO measurements to capture the holistic, lived experience of patients on investigational cancer therapeutics, there is limited incorporation of PROs in NMIBC interventional trials. These data serve as a call to action for PRO tool harmonisation and universal incorporation in NMIBC clinical trial design.