Examining factors underlying geographic disparities in early-onset colorectal cancer survival among men in the United States.

Background: Despite overall incidence reduction in colorectal cancer (CRC) the past 32 years, unexplained incidence and mortality rates have increased significantly in younger adults ages 20-49. To improve understanding of sex-specific differences among this population, we aimed to determine the variance in early-onset CRC (EOCRC) survival among US men diagnosed with CRC before age 50, while considering individual- and county-level CRC outcome determinants. Methods: Hotspots (i.e., counties with high EOCRC mortality rates) were derived from Centers for Disease Control and Prevention data from 1999-2017, and linked to SEER data for men aged 15-49 years with CRC. Cox proportional hazards models were used to compare CRC-specific survival probability and hazard in hotspots versus non-significant counties. A generalized R2 was used to estimate the total variance in EOCRC survival explained by clinicodemographic and county-level determinants. Results: We identified 232 hotspot counties for EOCRC-214 (92%) of which were in the South. In hotspots, 1,009 men were diagnosed with EOCRC and 31,438 in non-significant counties. After adjusting for age, race, tumor stage and grade, surgery, chemotherapy, radiation therapy, and marital status, men residing in hotspot counties had higher hazard of CRC-specific death (HR 1.24, 95% CI, 1.12-1.36). Individual/county-level factors explained nearly 35% of the variation in survival, and adult smoking served as the strongest county-level determinant of EOCRC survival. Conclusion: Distinct geographic patterns of EOCRC were predominantly located in the southern US. Survival after EOCRC diagnosis was significantly worse among men residing in hotspot counties.