INCLUSION OF OLDER ADULTS IN BLADDER CANCER CLINICAL TRIALS: A SYSTEMATIC REVIEW

Introduction: Bladder cancer (BdC) is primarily seen among older individuals, with a median age at diagnosis of 73 years(y). However, the older population is usually underrepresented in clinical trials (CT). This study aimed to evaluate the inclusion of older patients (OP) in BdC CT. Methods: A systematic search of PUBMED, Cochrane and Embase databases was done by two independent investigators for published studies under the search term ‘bladder cancer’. Filters: ‘phase II and III studies’ AND date (2000/1/1 – 2022/04/20) AND ‘controlled clinical trials’ AND language ‘english’. Randomized or controlled phase II and III trials of systemic therapies were included. Trials of intravesical therapies, radiotherapy and testing surgical techniques were excluded. Results: 1525 studies were found and 163 were initially selected. Of those, 46 were included, comprising 12593 patients. Conference papers, subanalysis, local therapies studies and with a single arm were excluded. The majority included were phase III (52.2%), of the metastatic (65.2%) or adjuvant (l5.2%) scenario, comparing multi-drug regimens (52.2%), with platinum-based therapies (65.2%), and had negative primary outcomes (65.2%). 69.5% were published in the last decade and 3 trials issued this year were included. Only 12 (26.1%) described the proportion of older adults: 33.3% of the trials published between 2000-2010 and 24.3% between 201 1-2022. The mean rate of OP inclusion was 52.3% and the median, 49.7% (47.9% in trials of 2000-2010 and 52.9% of 2011-2022). The older definition was variable, with most (52.9%) considering ≥ 65y (6.5% ≥ 70y; 2.2% ≥ 75y). Seven (15.2%) had a maximum inclusion age criteria, ranging from 65y to 80y. 94.6% had patients over 70y, but only 14% had a median age ≥ 70y. Only 11 studies had an older subgroup analysis of the primary endpoint and, although all had a positive result, the benefit for OP was only seen in 4 of them. None of the studies performed geriatric assessment and only one evaluated drug toxicity specifically in OP. Conclusion: Reports of older adults recruitment have not increased in the last decade in bladder cancer clinical trials. Despite these being the majority of BdC patients, the proportion of OP in CT remained stagnant and most of those trials did not analyze older-specific outcomes.