Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database
Authors: En Cheng, Holly N. Blackburn, Kimmie Ng, Donna Spiegelman, Melinda L. Irwin, Xiaomei Ma, Cary P. Gross, Fred K. Tabung, Edward L. Giovannucci, Pamela L. Kunz, Xavier Llor, Kevin Billingsley, Jeffrey A. Meyerhardt, Nita Ahuja, Charles S. Fuchs
Journal: JAMA Network Open (2021)

<h3>Importance</h3> While increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC. <h3>Objective</h3> To characterize the overall survival for individuals with early-onset CRC. <h3>Design, Setting, and Participants</h3> This cohort study used data from the National Cancer Database. Included individuals were ages 0 to 90 years and diagnosed with primary CRC from January 1, 2004, through December 31, 2015. Individuals diagnosed at ages 51 through 55 years were selected as the reference group and defined as later-onset CRC for this study. Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at that age in our population, given that these individuals disproportionately presented with earlier stage. All statistical analyses were conducted from January 4, 2020, through December 26, 2020. <h3>Exposures</h3> Early-onset CRC was defined as age younger than 50 years at diagnosis. <h3>Main Outcomes and Measures</h3> Overall survival was assessed by Kaplan-Meier analysis and Cox proportional hazards regression. <h3>Results</h3> Among 769 871 individuals with CRC (377 890 [49.1%] women; 636 791 White individuals [82.7%]), 353 989 individuals (46.0%) died (median [range] follow-up: 2.9 [0-14.0] years), 102 168 individuals (13.3%) had early-onset CRC, and 78 812 individuals (10.2%) had later-onset CRC. Individuals with early-onset CRC, compared with those diagnosed with CRC at ages 51 through 55 years, had a lower 10-year survival rate (53.6% [95% CI, 53.2%-54.0%] vs 54.3% [95% CI, 53.8%-54.8%];<i>P</i> &lt; .001) in unadjusted analysis. However, after adjustment for other factors associated with mortality, most notably stage, individuals with early-onset CRC had a lower risk of death compared with individuals diagnosed from ages 51 through 55 years (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93-0.96];<i>P</i> &lt; .001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88-0.90;<i>P</i> &lt; .001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84-0.92];<i>P</i> &lt; .001) and stages I (adjusted HR, 0.87 [95% CI, 0.81-0.93];<i>P</i> &lt; .001) and II (adjusted HR, 0.86 [95% CI, 0.82-0.90];<i>P</i> &lt; .001) and was absent among those diagnosed at ages 25 years or younger and stages III through IV. <h3>Conclusions and Relevance</h3> These findings suggest that there is a survival benefit for individuals with early-onset CRC compared with those diagnosed with CRC at later ages. Further study is needed to understand the underlying heterogeneity of survival among individuals with early-onset CRC by age and stage.