High Case Burden of Undetected Preclinical Early-Onset CRC

Researchers indicated that using observed incidence rates from patients with colorectal cancer alone to assess potential screening outcomes may underestimate cancer prevention benefits.

Using observed incidence rates from patients with colorectal cancer (CRC) aged 45-49 years alone to assess potential outcomes of earlier screening may underestimate cancer prevention benefits, according to this study published in JAMA Network Open.1

The researchers suggested that more detailed studies are necessary to determine what proportion of CRC cases that could be prevented or diagnosed at earlier stages.

“Despite increasing [early-onset colorectal cancer; EOCRC] rates and presentations with advanced-stage disease, possible reasons posed against earlier screening include an absolute incidence among patients aged 45 to 49 years that is considered relatively low and potentially diverting resources from higher-risk older patients with nonoptimized screening rates,” the authors wrote. “Our findings, however, suggest the presence of a high case burden of undetected preclinical EOCRC in younger patients, not reflected in observed SEER incidence rates.” 

Using data from the SEER 18 registries, which represents 28% of the US population, the researchers analyzed a total of 170,434 cases of CRC across 165,160 patients. Steep increases in the incidence of colorectal cancer in the SEER 18 registries was observed from 49-50 years of age (46.1%; 34.9 [95% CI, 34.1-35.8] to 51 [95% CI, 50-52.1] per 100,000 population). Additionally, steep rate increases from 49-50 years of age were also found in all US regions, men and women, black and white populations, and in colon and rectal cancers. 

The rate ratio incidence increase in the SEER 18 registries from 49-50 years of age was significantly higher than earlier 1-year age transitions (1.46; 95% CI, 1.43-1.51]). Moreover, steep rate increases in the SEER 18 registries were seen from 49-50 years of age in localized-stage (75.9%’ 11.2 [95% CI, 10.7-11.7] to 19.7 [95% CI, 19.0-20.3] per 100.000) and regional-stage (30.3%; 13.2 [95% CI, 12.7-13.8] to 17.2 [95% CI, 16.7-17.8] per 100 000) colorectal cancers.

Of the 9,474 cases of colorectal cancer in the SEER 18 registries diagnosed from 2000=2015 among those aged 50 years, a total of 8,799 were invasive.

“These findings suggest a high case burden of preclinical, undetected EOCRC in younger patients (ultimately diagnosed via screening uptake at 50 years) that is not reflected in observed SEER incidence rates,” the authors wrote. “Hence, we cannot reliably compare CRC incidence rates between individuals younger than 50 years and those 50 years or older to estimate effects of earlier screening.”

Researchers indicated that, in addition to studies determining the proportion of CRC cases diagnosed at 50 years through screening vs diagnostic testing, modeling studies, incorporating the steep incidence inflection point at 49-50 years, could also be conducted to estimate what the incidence rate increase at 45 years would be with earlier screening. Furthermore, studies such as this could also focus on cost-benefit analysis, quality-adjusted life-years, and other metrics to further interpret the effects of earlier screening.

According to Memorial Sloan Kettering Cancer Center, the number of cases of CRC in people under 50 is expected to almost double by 2030. Of those under 50 with colorectal cancer, most do not have a family history of the disease.2


1. Abualkhair WH, Zhou M, Ahnen D, Yu Q, Wu X, Karlitz JJ. Trends in Incidence of Early-Onset Colorectal Cancer in the United States Among Those Approaching Screening Age. JAMA Network Open. doi:10.1001/jamanetworkopen.2019.20407.

2. Memorial Sloan Kettering Cancer Center. Colorectal Cancer before 50. Memorial Sloan Kettering Cancer Center Website. Published 2020. mskcc.org/cancer-care/types/colorectal/colorectal-cancer-young-adults?gclid=CjwKCAiAyeTxBRBvEiwAuM8dnfV2ZljeqqmDd7Wf5lwBS7vwvlZpbOUkD8upKJg8ghuraOnMo-C9EBoCkT0QAvD_BwE. Accessed February 4, 2020.