EBM Focus articles provide concise summaries of clinical trials most likely to inform clinical practice curated by the DynaMed® editorial team.

Global guideline recommendations for colorectal cancer screening have historically recommended initiation at age 50, a cutoff arbitrarily set in early trials. In 2018, however, the American Cancer Society (ACS) suggested 45 as the age of initiation based on epidemiologic data and microsimulation modeling. Now, in a swift shift in direction, an international panel has released a clinical practice guideline that recommends screening adults aged 50-79 with a 15-year risk more than three percent using any one of single colonoscopy, single sigmoidoscopy, or annual or biennial FIT testing – and no screening for people with a 15-year colorectal cancer risk less than three percent.

These recommendations rely on the United Kingdom (UK) QCancer calculator to predict the 15-year risk using age, sex, ethnicity, body mass index, smoking status, UK postal code, family history of gastrointestinal cancer, and personal history of certain cancers, diabetes, ulcerative colitis, and/or colonic polyps. Microsimulation modeling was again used to develop these recommendations due to a lack of randomized trials evaluating colonoscopy and FIT testing. The only new high-quality data not considered in the ACS guidelines were trial extension data on sigmoidoscopies.

While personalization of cancer screening recommendations is appealing, there are major concerns with these recommendations.

  • First, while we still somehow don’t have high-quality data on most of the methods of colorectal cancer screening, the epidemiologic data we do have show that there are significant environmental contributors to colorectal cancer risk, with geographic location being one of the most important. Risk can vary significantly in places just one or two miles away from each other, so while this calculator may adequately predict risk in the UK (if answered perfectly, which we’ll get to next), we can’t extrapolate the same risk to those living elsewhere. At best, then, these guidelines are only valid for the UK population.
  • Second, the calculator requires patients to know their family history in order to accurately stratify their risk. If that one box is checked or unchecked, the risk can change significantly and move a patient from no screening to screening. Worse, the “family history of gastro-intestinal cancer” box doesn’t distinguish between a patient with a second cousin who had pancreatic cancer at age 80 or a brother with colon cancer at age 30.
  • Third, while these are technically evidence-linked guidelines, it seems that the panel at times appraised the evidence and then ignored it when making their recommendations. They admit that the decision to use a three percent 15-year risk as the cutoff for screening was arbitrary. The presumption that most people would choose screening if their 15-year risk was more than three percent was based almost entirely on the opinions of this group, which included clinical and methodological experts as well as three patient representatives.
  • Finally, there are several notable inconsistencies. The guideline group did not make any assessment of multi-target stool DNA testing every three years, a widely used screening option. Additionally, the data suggest that biennial FIT testing does not have a clinically significant impact on cancer-specific or all-cause mortality, but the panel still chose to include it in the recommendations. Another inconsistency is the decision to assess 15-year risk rather than 10-year risk, which is the more conventional risk used and is more in line with the natural progression of colorectal cancer.

Risk-based colorectal cancer screening makes sense conceptually, and the use of a validated decision aid for screening may eventually become common practice. However, in our assessment, these guideline recommendations based on the QCancer calculator have some significant flaws. We need higher quality data to determine the right test for the right patient at the right time when it comes to colorectal screening.

For more information, see the topic Colorectal Cancer Screening in DynaMed.