In February 2019, Fight Colorectal Cancer (Fight CRC) convened researchers from around the world to identify and prioritize what is causing the dangerous rise in cases of early-age onset colorectal cancer (EAO CRC). 

Since that meeting, the EAO CRC working group has published a meeting summary and a commentary in Gastro, reconvened in smaller groups at conferences such as Digestive Disease Week (DDW), and is currently planning a symposium in Madrid, Spain with working group member, Dr. Jose Perea. Working group members are also leading research in their respective fields. 

This is part one of a five-part series highlighting different areas of research being conducted by Fight CRC working group members to understand where the science is headed, and what it means for our community of patients.

Summary of the Research: EAO CRC

To better understand the increase in the incidence of colorectal cancer from ages 49 to 50 years old (when screening begins for average risk populations), researchers conducted a cross-sectional study between 2000 and 2015 looking at colorectal cancer incidence rates.

In contrast to prior studies in which wide age group blocks were analyzed (for example age 30-39, 40-49, etc.) this study was more of a “high-definition” analysis in which incidence rates were examined in one-year-age increments. They stratified by regions in the U.S. (South, West, Northeast and Midwest), sex, race, disease stage, and location of tumor (rectum vs. colon). 

In total, there were 170,434 colorectal cancer cases and 165,160 patients analyzed. Researchers found a steep increase in incidence rates between the ages of 49 to 50 across all regions, sexes, and white and black populations in rectal and colon cancers and in localized and regional stage cancers.

To better understand what these findings mean, we reached out to lead author Dr. Jordan Karlitz to gain insight on the significance of this work. 

Why is This Paper Impactful?

Given debate and differing guidelines over when average-risk colorectal cancer screening should begin (age 45 vs age 50), we felt that performing a detailed incidence rate analysis in one year age increments (as opposed to age range blocks as has been done in the past)  would be revealing. In particular, we were interested in the transition from age 49 to 50, as this is when average-risk screening has historically been recommended. 

What Does This Mean for the Debate About the Screening Guideline? What Do You Recommend for Patients and Advocates?

Our analysis revealed a 46% spike in colorectal cancer incidence rates from age 49 to 50.  Stage stratification revealed that 93% of the cases were invasive (beyond in situ stage), which may require more aggressive treatment, including surgery and possibly chemotherapy and radiation. Given that cancers may take several years to grow, these lesions were likely present and developing for several years prior while patients were in their 40s, but ultimately detected with screening initiation at age 50.

These findings support a significant undetected preclinical colorectal cancer burden in those under age 50, which is not reflected in observed incidence rates. Hence, relying on observed incidence rates of those 45-49 years of age alone to assess potential impacts of earlier screening may underestimate cancer prevention benefits. 

It is important to highlight that an undetected, preclinical-cancer-case burden may be present in patients of any age, including those over age 50, which may be compounded by non-optimized CRC screening rates. But a key aspect of our study is that we assessed this preclinical burden in those approaching screening age, which is important given ongoing debates on when screening should be initiated.  We are hoping this data can contribute to the earlier screening debates and can be taken into consideration by those developing screening guidelines.

Another key message is that despite debates over screening age initiation, screening rates are not optimal in general, particularly in younger patients (28-47% in those aged 50-54 from 2000-2015 according to prior studies). So it is really important that patients discuss getting screened with their healthcare providers. In addition, given rising rates of early-onset colorectal cancer, concerning symptoms should prompt thorough evaluations and cancer family histories must be known as a family history may require much earlier screening.

Comparing observed incidence rates between those under age 50 and those 50 and older with regard to estimating the potential impact of earlier screening initiation can be misleading. This is because in general, observed incidence rates in those age 50 and older reflect both average-risk screening detected cases in addition to diagnostically detected cases (due to symptoms), whereas in those under age 50, incidence rates would be expected to primarily reflect diagnostically detected cases or higher-risk screened groups (cancer family history) because average-risk screening has historically not been performed. 

Observed incidence rates of those in their mid to late 40s would be expected to be significantly lower than those in their early 50s, not because the underlying case burden is substantially lower, but because many CRCs may be present yet undetected until diagnosed at 50 years when screening is ultimately initiated.

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