Spotlight on early-onset CRC

Three recent studies focused on early age-onset colorectal cancer (CRC), assessing changes in incidence over time, differences in survival based on age at CRC diagnosis, and the prevalence of colorectal neoplasia (CRN) and advanced CRN in different age groups at average risk.

The first study found that CRC incidence did not begin to increase for adults younger than age 50 years until 1981 to 1985, indicating that the increase may be attributable to risk factors, such as obesity, that have been changing in recent birth cohorts. Researchers evaluated age- and sex-specific trends in CRC incidence rates from 1935 to 2017 using data from the Connecticut Tumor Registry (CTR), the oldest population-based cancer registry in the U.S. They also evaluated trends by tumor subtype. In addition, they compared data between the CTR and the SEER 9 Registries (1975 to 2017), which include the CTR. Results were published online on May 28 by Gastroenterology.

CRC incidence significantly increased in women ages 25 to 49 years in the CTR at an annual rate of 1.75% (95% CI, 1.18% to 2.32%) from 1985 to 2017, whereas the prior three decades (1953 to 1985) had declining incidence. In men ages 25 to 49 years, CRC incidence was stable from 1935 to 1974 before a nonsignificant decrease from 1974 to 1981 and a significant increase from 1981 to 2017 (annual percent change, 1.99%; 95% CI, 1.55% to 2.43%). When analyses were stratified by subtype, only the incidence of rectal cancer significantly increased in recent decades in women and men ages 25 to 49 years. In adults ages 50 years and older, CRC incidence rates significantly decreased across most time points from 1985 to 2017, including for distal colon, proximal colon, and rectal cancer. Age-specific incidence trends in the CTR paralleled those in the SEER 9 Registries from 1975 to 2015, the period with overlapping data from both sources. Among other limitations, the study did not evaluate stage-specific incidence trends due to substantial missing data in early years, the authors noted.

The second study found that there is a survival benefit associated with onset of CRC at an earlier age compared with later age-onset CRC, reinforcing the importance of early detection. Researchers used data from the National Cancer Database to assess survival rates among individuals ages 0 to 90 years who were diagnosed with primary CRC from 2004 through 2015. They selected those diagnosed at ages 51 through 55 years as the reference group, defined as later-onset CRC, and those diagnosed at younger than age 50 years as early-onset CRC. The researchers excluded individuals diagnosed at age 50 years to minimize an apparent screening detection bias at that age, given that these patients disproportionately presented with earlier-stage CRC. The primary outcome was overall survival, defined as the time from cancer diagnosis until death or the date of last contact. Results were published June 16 by JAMA Network Open.

Among 769,871 individuals with CRC (49.1% women; 82.7% White), 46.0% died during a median follow-up of 2.3 years (range, 0 to 14.0 years). Overall, 13.3% had early-onset CRC, and 10.2% had later-onset CRC. Compared with those diagnosed with CRC at ages 51 through 55 years, individuals with early-onset CRC had a lower 10-year survival rate (53.6% [95% CI, 53.2% to 54.0%] vs. 54.3% [95% CI, 53.8% to 54.8%]; P<0.001) in unadjusted analysis. However, after adjustment for other factors associated with mortality (particularly CRC stage), those with early-onset CRC had a lower risk of death compared to those with later-onset CRC (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93 to 0.96]; P<0.001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88 to 0.90; P<0.001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84 to 0.92]; P<0.001) and at stages I (adjusted HR, 0.87 [95% CI, 0.81 to 0.93]; P<0.001) and II (adjusted HR, 0.86 [95% CI, 0.82 to 0.90]; P<0.001) and was absent among those diagnosed at ages 25 years or younger and at stages III through IV. Among other limitations, data on causes of death were not available, so calculation of CRC-specific mortality was not possible, the study authors noted.

An accompanying commentary added that the U.S. Preventive Services Task Force (USPSTF) recently reduced the CRC screening age to 45 years from 50 years (B recommendation). “While CRC diagnoses and CRC-related deaths have been trending up in patients aged 50 years and younger, one would expect this trend to slow as the new screening age of 45 years or older is implemented,” the editorialists wrote. “CRC diagnoses in patients younger than 45 years continue to represent a small percentage of all CRC diagnoses, but the findings [of this study] provide optimism about treatment outcomes in these patients. More information is needed to understand how the updated USPSTF CRC screening recommendations could impact mortality in patients screened between the ages of 45 and 50 years.”

The third study found that the rate of advanced CRN in individuals ages 45 to 49 years was similar to that observed in those ages 50 to 59 years, suggesting that expanding screening to this population may result in earlier identification and surveillance of those at increased risk for CRC. Researchers conducted a systematic review of three databases from inception through July 2020 that reported colonoscopy findings in average-risk individuals younger than age 50 years. The primary outcomes were early age-onset CRN and advanced CRN prevalence. Results were published online on June 9 by Gastroenterology.

A total of 17 studies published between 2002 to 2020 were included, encompassing 51,811 average-risk individuals from four continents. The pooled rates of early age-onset CRN and advanced CRN were 13.7% (95% CI, 11.2% to 16.8%) and 2.2% (95% CI, 1.6% to 3.1%), respectively. The prevalence of CRC was 0.05% (95% CI, 0.03% to 0.08%). Rates of early age-onset CRN were higher in men compared to women (risk ratio, 1.71; 95% CI, 1.49 to 1.98) and were highest in the U.S. (15.6%; 95% CI, 12.1% to 19.7%) compared to Europe (14.9%; 95% CI, 6.9% to 29.3%), East Asia (13.4%; 95% CI, 10.3% 17.2%), and the Middle East (9.8%; 95% CI, 7.8% to 12.2%) (P=0.04). The rates of early age-onset advanced CRN in those ages 45 to 49 years and ages 50 to 59 years were 3.6% (95% CI, 1.9% to 6.7%) and 4.2% (95% CI, 3.2% to 5.7%), respectively (P=0.69). Generalizability to a specific population, such as average-risk individuals in the U.S., is restricted because the review included diverse international cohorts, among other limitations, the study authors noted.