Clinical and Genomic Profiling of Early-Onset Bladder Cancer Identifies Key Alterations and Therapeutic Targets
Christopher J. Magnani, Vincent D. D'Andrea, Guilherme Garcia Barros, Zhiyu Qian, John Ernandez, Kendrick Yim, Adam S. Kibel, Steven L. Chang, Matthew Mossanen, Mark A. Preston, Adam S. Feldman, Bernard H. Bochner, David B. Solit, Eugene J. Pietzak, Kent W. Mouw, Filipe L.F. Carvalho, Timothy N. ClintonPurpose:
Younger patients with bladder cancer have fewer environmental exposures or risk factors, suggesting that the molecular pathways implicated in early-onset disease differ from older patients. Dissecting the genomic profiles of early-onset tumors may inform targeted treatment strategies for young patients. We compared the frequency of somatic mutations in early-onset bladder cancer, defined as a diagnosis before the age of 55 years, which encompasses the youngest patients in approximately 1 in 10 diagnoses based on national registries.
Material and methods:
We assessed 2 institutional cohorts: the Mass General Brigham Young Cystectomy Cohort (MGB-YCC, n = 134 patients) from 2008 to 2023 and the Memorial Sloan Kettering-IMPACT bladder cancer cohort (MSK-IMPACT, n = 1271 including n = 207 cystectomy and n = 811 transurethral resection (TUR) specimens) from 2014 to 2021. Clinical outcomes were compared with patients undergoing cystectomy in the National Surgical Quality Improvement Program (NSQIP, n = 10,848).
Results:
MGB-YCC and MSK-IMPACT cohorts were predominantly male (> 75%), and younger patients had lower rates of smoking history or muscle-invasive disease. MGB-YCC demonstrated more patients with continent diversions (51.5% vs 14.9%) than the older population in NSQIP, although complication rates were similar. Genomic characterization of MGB-YCC demonstrated enrichment in younger patients of TP53 (65% overall, 83% < 50-year- old,
Conclusions:
Our results indicate that early-onset bladder cancer is a distinct patient population that has disease driven by specific somatic mutations, some of which represent therapeutic targets. This suggests potential benefits of genomic tumor profiling in guiding personalized treatment.