Introduction: Age disparity in patients with non-muscle-invasive bladder cancer (NMIBC) exists. Whether this is due to differences in cancer care or tumour biology is unclear. We sought to investigate age disparities in NMIBC using individual patient-level data from two cohorts: the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and the publicly available UROMOL dataset. Methods: SEER-Medicare linked data was used to identify patients, aged =66 years, with clinical stage Ta, Tis and T1 NMIBC between 2005-2019 (n= 32 225). Multivariable competing-risks Cox regression analyses were used to examine the association between age and recurrence (defined as receipt of TURBT =3 months after index diagnosis of NMIBC or progression), progression (defined as receipt of definitive treatment for bladder cancer) and bladder cancer-specific mortality rates after adjusting for demographic-, cancer- and treatment-related variables. Using the UROMOL cohort (n=834), age disparities across transcriptomic, genomic and spatial proteomic domains were assessed. Differences between groups were testing using Pearson’s Chi-square test or Fisher’s test for categorical variables. Results: Analysis of the SEER-Medicare cohort revealed 10-year recurrence rates of 60.9%, 61.1% and 60.4% in patients aged 66-70yrs, 71-80yrs and =81yrs, respectively; 10-year progression rates of 29.3%, 32.2% and 38.2%, respectively; and 10-year bladder-cancer specific mortality rates of 5.5%, 7.9% and 14.3%, respectively. Age = 81yrs was associated with a higher risk of progression (HR 1.32, 95% CI 1.25-1.40, p<0.001) and bladder cancer-specific mortality (HR 2.58, 95% CI 2.27-2.95, p<0.001). Analysis of UROMOL 2021 transcriptomic classes revealed that Class 2a was more frequently observed in older patients (34% in >75yrs vs. 22% in =65yrs; p=0.004). Compared to patients <65yrs, those aged >75yrs were more likely to have TP53 pathway change (54% vs. 38%; p=0.032). UROMOL genomic class 3 was more frequently observed in patients >75yrs (42% vs. 24%; p=0.001), who also had higher amounts of altered genome (median: 337.7Mb vs. 168.2Mb; p<0.001). No significant differences were observed in immune cell infiltration scores between age groups. Conclusions: Among SEER-Medicare patients with NMIBC, advanced age is associated with higher risks of progression and bladder-cancer specific mortality. These results reflect age-related molecular biological differences observed across transcriptomic and genomic domains. SOURCE OF Funding: Niyati Lobo was supported by The Urology Foundation-Fulbright Scholar Award.
