Association of Age with Non–muscle-invasive Bladder Cancer: Unearthing a Biological Basis for Epidemiological Disparities?

Background Age disparity in patients with non–muscle-invasive bladder cancer (NMIBC) exists. Whether this is due to differences in adequate cancer care or tumour biology is unclear. Objective To investigate age disparities in NMIBC using the Surveillance, Epidemiology, and End Results (SEER)-Medicare and UROMOL datasets. Design, setting, and participants The SEER-Medicare data were used to identify patients with clinical stage Ta, Tis, and T1 NMIBC between 2005 and 2017 (n = 32 225). Using the UROMOL cohort (n = 834), age disparities across transcriptomic, genomic, and spatial proteomic domains were assessed. Outcome measurements and statistical analysis For the SEER-Medicare data, multivariable competing-risk regression was used to examine the association between age and recurrence, progression, and bladder cancer–specific mortality (BCSM). For the UROMOL cohort, multivariable general linear model and multinomial logistic regression were performed to evaluate the association between age and tumour biology. Results and limitations An analysis of the SEER-Medicare cohort revealed 5-yr recurrence rates of 55.2%, 57.4%, and 58.9%; 5-yr progression rates of 25.6%, 29.2%, and 36.9%; and 5-yr BCSM rates of 3.9%, 5.8%, and 11.8% in patients aged 66–70, 71–80, and ≥81 yr, respectively. After multivariable adjustment, age ≥81 yr was associated with a higher risk of recurrence (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.03–1.12; p = 0.001), progression (HR 1.32, p < 0.001), and BCSM (HR 2.58, p < 0.001). UROMOL2021 transcriptomic class 2a was most frequently observed in patients with advanced age (34.0% in ≥76 yr vs 21.6% in ≤65 yr; p = 0.004), a finding confirmed on multivariable analysis (risk ratio [RR] 3.86, p = 0.002). UROMOL2021 genomic class 3 was observed more frequently in patients aged ≥76 yr (4.9% vs 24.2%; p = 0.001). Limitations include the definitions used for recurrence and progression, which may lead to under- or overestimation of true rates. Conclusions Among SEER-Medicare patients with NMIBC, advanced age is associated with inferior oncological outcomes. These results reflect age-related molecular biological differences observed across transcriptomic and genomic domains, providing further evidence that innate tumour biology contributes to observed disparities in NMIBC outcomes. Patient summary Older patients with non–muscle-invasive bladder cancer have worse oncological outcomes than younger patients. Some of this age disparity may be due to differences in tumour biology.