medRxiv : the preprint server for health sciences · 2026
Clinical and genomic profiling of early-onset bladder cancer identifies key alterations and therapeutic targets.
СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
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Magnani Christopher J, D'Andrea Vincent D, Barros Guilherme Garcia, Qian Zhiyu, Ernandez John, Yim Kendrick, Kibel Adam S, Chang Steven L, Mossanen Matthew, Preston Mark A, Feldman Adam S, Bochner Bernard H, Solit David B, Pietzak Eugene J, Mouw Kent W, Carvalho Filipe L F, Clinton Timothy N
Аннотация
PURPOSE: Younger patients with bladder cancer typically have fewer environmental exposures or risk factors, suggesting that the molecular pathways implicated in early-onset disease differ from those in 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 about 1 in 10 diagnoses based on national registries.
MATERIAL AND METHODS: We assessed two institutional cohorts: the Mass General Brigham Young Cystectomy Cohort (MGB-YCC, n=134 patients) from 2008-2023 and the Memorial Sloan-Kettering-IMPACT bladder cancer cohort (MSK-IMPACT, n=1271) from 2014-2021. Clinical outcomes of MGB-YCC were also compared with published data from patients undergoing cystectomy in the National Surgical Quality Improvement Program (NSQIP, n=10,848) from 2008-2013.
RESULTS: Both the MGB-YCC and MSK-IMPACT cohorts were predominantly male (>76%), and younger patients were less likely to have a history of smoking 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 KMT2D mutations almost exclusively in the youngest patients (83% <45-years-old, p=0.008). MSK-IMPACT revealed a significant increase in FGFR3 mutations in younger patients (p<0.001).
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.
MATERIAL AND METHODS: We assessed two institutional cohorts: the Mass General Brigham Young Cystectomy Cohort (MGB-YCC, n=134 patients) from 2008-2023 and the Memorial Sloan-Kettering-IMPACT bladder cancer cohort (MSK-IMPACT, n=1271) from 2014-2021. Clinical outcomes of MGB-YCC were also compared with published data from patients undergoing cystectomy in the National Surgical Quality Improvement Program (NSQIP, n=10,848) from 2008-2013.
RESULTS: Both the MGB-YCC and MSK-IMPACT cohorts were predominantly male (>76%), and younger patients were less likely to have a history of smoking 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 KMT2D mutations almost exclusively in the youngest patients (83% <45-years-old, p=0.008). MSK-IMPACT revealed a significant increase in FGFR3 mutations in younger patients (p<0.001).
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.