To address this question, we conducted an integrative analysis leveraging two distinct datasets. First, we utilised the SEER-Medicare database to examine the association of age with oncological outcomes, namely recurrence, progression, and bladder cancer-specific mortality. Next, we used data from a multi-omics analysis of the UROMOL dataset to assess age disparity in tumour biology.2
Our analysis of the SEER-Medicare cohort unveiled disparities across age groups, with older patients exhibiting higher risks of recurrence, progression, and bladder cancer-specific mortality. Notably, patients aged >81 years demonstrated significantly increased risks of inferior outcomes after multivariable adjustment. Similarly, subsequent analysis of the UROMOL cohort revealed age disparities in tumour biology across transcriptomic and genomic domains. Firstly, UROMOL2021 transcriptomic class 2a and 2b were most frequently observed in patients > 76 years. The former represents a high-risk group of tumours with a propensity for multiple progression events.2 Indeed, patients with class 2a tumours demonstrate the worst progression-free survival, followed by those with class 2b tumours.2 Secondly, older patients were more likely to exhibit UROMOL2021 genomic class 3 tumours, which are associated with the highest levels of chromosomal instability and are an independent prognostic factor for recurrence and progression.2
Our study has several limitations. The SEER database does not capture recurrence or progression, so the definitions used in this study may have led to over- or underestimation of true recurrence and progression risks. More broadly speaking, the study did not explore disparities in cancer care- do older patients present with more aggressive disease because of a delay in diagnosis and do they receive guideline-concordant care to the same extent as younger patients? Addressing these questions is key to achieving a comprehensive understanding of age disparities in NMIBC outcomes.
Nevertheless, to our knowledge, this is the first study to demonstrate age-related changes in tumour biology across transcriptomic and proteomic domains. As the global population ages, bladder cancer incidence is expected to increase. Yet, older individuals with cancer are frequently under-represented in research endeavours, particularly in randomized controlled trials which often shape the standard of care. Our study highlights the importance for researchers to recognize the diversity of NMIBC tumour biology across age groups and tailor therapeutic strategies accordingly, ensuring personalized care for all patients.
Written by:
- Niyati Lobo, MD, Department of Urology, Royal Free London NHS Trust, London, UK; Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Ashish Kamat, MD, MBBS, Professor of Urology, and Wayne B. Duddleston Professor of Cancer Research, University of Texas, MD Anderson Cancer Center, Houston, TX
- Babjuk M, Burger M, Capoun O, et al. European Association of Urology guidelines on non-muscle-invasive Bladder Cancer (Ta, T1, and carcinoma in situ). Eur Urol 2022;81:75–94.
- Lindskrog SV, Prip F, Lamy P, et al. An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle- invasive bladder cancer. Nat Commun 2021;12:2301.