Empirical Evidence Points to Benefit of Earlier Colon Cancer Screening

Women who underwent sigmoidoscopy or colonoscopy for colorectal cancer (CRC) screening at ages 45 to 49 had a lower risk of colorectal cancer (CRC) when compared to those who started just 5 years later, an analysis of the Nurses’ Health Study II showed.

Through age 60, screening initiation at the younger age range led to an absolute reduction of 72 CRC cases per 100,000 women compared with initiation at 50 to 54 years, reported Mingyang Song, MD, ScD, of the Harvard T.H. Chan School of Public Health in Boston, and colleagues.

Epidemiologic data has shown a 51% increase in CRC incidence in younger individuals over the past 50 years, the group noted in JAMA Oncology, leading both the American Cancer Society and U.S. Preventive Services Task Force to lower the recommended starting age for screening in average-risk adults to 45 years.

But the guideline changes were based primarily on microsimulation models, according to Song and colleagues. Empirical evidence supporting earlier screening has been limited, they suggested, as has data examining the association between earlier screening, specific CRC risk factors, and stage- and site-specific CRC incidence.

When looking at subsites, the researchers found that initiating screening before age 50 was primarily linked to a lower risk of distal CRC: proximal (HR 0.58, 95% CI 0.33-1.02), rectum (HR 0.35, 95% CI 0.20-0.60), distal (HR 0.13, 95% CI 0.05-0.33).

And they found that the HRs for CRC stage at diagnosis was similar regardless of screening initiation age:

• Stage I/II: HR 0.48 for ≥50 years (95% CI 0.29-0.81)
• Stage I/II: HR 0.32 for <50 years (95% CI 0.17-0.58)
• Stage III/IV: HR 0.39 for ≥50 years (95% CI 0.22-0.68)
• Stage III/IV: HR 0.28 for <50 years (95% CI 0.15-0.51)

“Our findings support guidelines from the past 4 years that recommend screening for CRC at 45 years of age and provide empirical evidence for patients, physicians, and policy makers to consider when making decisions about CRC screening in a younger population,” the researchers concluded.

In an accompanying editorial, Gregory Calip, PharmD, MPH, PhD, of the University of Illinois in Chicago, and coauthors cautioned that “the overall cohort in the study was not a true screening population.”

“Women included in the study were mostly white health care professionals, limiting generalizability and the ability to understand racial and ethnic inequities in the incidence of CRC or screening patterns among adults younger than 50 years,” the editorialists wrote. “Of more importance, the screening population was not at average risk for CRC. This was apparent given the higher proportion of patients with family history of CRC among those who initiated endoscopy before 45 years of age and from 45 to 49 years of age (22.3% and 23.0%, respectively).”

For their study, Song and colleagues examined data on 111,801 women from the Nurses’ Health Study II who were followed from 1991 through 2017. Nearly all participants were white (92%), and the median age was 36 at enrollment. Participants were generally healthy. Women were excluded from the analysis if they had a history of colorectal polyps, inflammatory bowel disease, or cancer (except for non-melanoma skin cancers).

Every 2 years, each participant was asked if they had undergone sigmoidoscopy or colonoscopy, and if so, whether it was for routine screening, symptoms, or a family history of CRC.

Overall, there were 519 CRC cases detected over the 26-year study period: 36 in those who initiated screening before age 45 years, 35 cases in women 45 to 49 years, 78 in those ages 50 to 54, and 35 cases in women who started screening at age 55 or older. Nearly two-thirds of the cases were found in women who did not undergo endoscopy.

Compared to those who first underwent an endoscopy at 50 or later, women who initiated endoscopy at 49 years or younger had a lower prevalence of diabetes, hypertension, hypercholesterolemia, and cancer, but were more likely to have a family history of cancer.

Overall, multivariable analysis showed that undergoing endoscopy was associated with a significantly reduced risk of CRC incidence at any starting age compared with no endoscopy:

• <45 years: HR 0.37 (95% CI 0.26-0.53)
• 45 to 49 years: HR 0.43 (95% CI 0.29-0.62)
• 50 to 54 years: HR 0.47 (95% CI 0.35-0.62)
• ≥55 years: HR 0.46 (95% CI 0.30-0.69)

Initiating endoscopy prior to age 50 was also linked to a lower risk of receiving a CRC diagnosis through age 55 compared to no endoscopy.

There were 89 CRC-related deaths documented during follow-up. On multivariable analysis, no association was seen between initiating endoscopy before age 50 and the risk of CRC-related mortality: HR of 0.59 for screening before age 50 (95% CI 0.28-1.28) and an HR of 0.42 for screening at 50 years or later (95% CI 0.23-0.78). The researchers noted, however, that the power for a mortality benefit was limited.