Missed opportunity: PROMs as primary endpoints in bladder cancer trials.

Abstract

682 Background: Bladder cancer is the sixth most common malignancy in the United States. Recent advances in treatment paradigm have changed the landscape of bladder cancer. Patient-reported outcome measures (PROMs) are measures of symptom burden and health related quality of life (HRQoL) that come directly from the patient, without clinician interpretation. PROMs can be the intervention and/or the outcome in a trial. We aimed to evaluate the trends in the usage of PROs for patients with muscle invasive bladder cancer (MIBC) and locally advanced or metastatic bladder (mBC) cancer as a measure of endpoints across global clinical trial databases. Methods: We searched the clinicaltrials.gov database for phase III trials involving muscle invasive, locally advanced and metastatic bladder cancer patients from 1990 to 2024. The data extraction included primary and secondary endpoints, PROMs, PRO parameters, and clinical trial duration. Descriptive statistics derived were used to summarize the data. Results: Fifty-four trials were included in the analysis, out of which 64.8% (n=35) were for mBC and 35.1% (n=19) for MIBC. Twenty-nine trials (53.7%) included PROMs as endpoint measures, more than half in MIBC (n=16, 55%). Approximately one third (n=13/35) of mBC included PROMs in their trials (37.1%) whereas (84.2%) included PROMs in MIBC trials (n= 16/19). None of the studies reported PROs as a primary outcome measure, twenty-three studies (79%) reported PROs as a secondary outcome, and only one (3.4%) reporting it as both primary and secondary outcome measure. In mBC nine trials (56.25%) in the 1 st line setting, six studies (37.5%) in the 2 nd line setting and one trial (6.25%) labelled as adjuvant after radiation. In MIBC trials, three studies (23%) were in the adjuvant setting, five studies (38%) in the neoadjuvant setting and one trial (8%) involving both adjuvant & neoadjuvant, and four studies (31%) in the chemoradiotherapy setting. Eleven different symptom domains were utilized to measure PROs across both the groups. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ C30) and the EuroQOL 5-dimension 5-level Questionnaire (EQ-5D-5L) were the most frequently utilized PRO scales, being used in 62.5% and 37.5% of PRO reporting studies respectively. Conclusions: PROMs are increasingly used in bladder cancer trials, especially for MIBC. Approximately one-third of the trials included PROMs, yet none utilized them as primary endpoints, indicating a missed opportunity to truly understand treatment impact from the patient's perspective. Future research should prioritize PROMs as primary outcome measures to ensure patient-centered care and improve quality of life for bladder cancer patients. Further efforts are needed to standardize the current available scales to measure PROs.