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July 15, 2016

Prevention Task Force Recommendations on Colon Cancer: Practice changing discoveries from the Case CCC

Colorectal cancer remains the second leading cause of cancer death in this country, though over the past decade, both the incidence and mortality have been declining.  Colorectal screening is universally recommended as a means to detect premalignant adenomas as well as early stage cancer, but almost 40% of the age eligible population is not up to date with screening.  Although there are at least six different available modalities, based on available evidence, the 2008 United States Preventive Services Task Force (USPSTF) guidelines limited their screening recommendations to one of three strategies, colonoscopy every 10 years, stool occult blood testing yearly, or a combination of flexible sigmoidoscopy and occult blood testing.  Other guidelines, such as that of the American Cancer Society recommended a broader range of tests, but prioritized those that involved direct endoscopic or radiographic visualization of the colon.  This week, the USPSTF updated the 2008 guidelines and in contrast to the previous version, no longer limits the scope of recommended tests.

The 2016 guidelines, which now include the commercially available stool DNA panel, CT colonography and sigmoidoscopy alone, as well as the previously recommended tests, now give clinicians and patients a larger menu of testing options.  The rationale for this departure from the earlier version is that there are essentially no data to directly compare the efficacy of more than one method, and based on individual characteristics and personal preferences, certain procedures may be more appropriate for that specific patient.  In addition, the overall adherence may be greater if patients are given a choice of screening methods.  As in the previous version, these guidelines recommend initiating screening at age 50, reassessing the benefit of screening between ages 75 and 85, and screening above age 85.  Notable limitations of the guidelines are the lack of stratification by ethnicity, with other agencies recommending routine screening in African Americans at age 45, and the lack of recommendations for follow up after polyp removal (surveillance).  Also, they acknowledged but did not address the rise in colon cancer incidence in individuals less than 50 years of age, though some of the microsimulation models that help inform guidelines recommend universal initiation of screening at age 45.  Taken together, the revised USPSTF guidelines echo the adage that the best screening test is the one that gets done and give patients and providers additional testing options.

In addition, the U.S. Preventive Services Task Force posted a draft recommendation statement supporting low-dose aspirin therapy for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in patients ages 50-59 who have an increased risk of heart attack and stroke. The task force recommended physicians make individual decisions on preventive aspirin therapy for patients ages 60-69 at increased risk for CVD and cancer.  

Of note, this is as close as it gets in the prevention and screening world to practice changing recommendations based on research. And, Sandy Markowitz and his multi-center team led a number of studies that led to these recommendations. The Markowitz team were pioneers of the field of stool DNA screening using methylated DNA, inventing the first commercial implementation of the technology, performing the first NIH funded clinical trials of the approach (through their SPORE and EDRN grants). Their studies were instrumental in the development of the DNA stool test now recommended.

Moreover, the Markowitz team were also progenitors in discovering the role of 15-PGDH in regulating the prostaglandin pathway of colon carcinogenesis, and in then making the seminal insight that this pathway also controlled responsiveness to NSAID and aspirin chemoprevention, demonstrating first in mice models, and then in high impact translational human studies, that low 15-PGDH confers resistance to chemopreventive activity of aspirin and celecoxib.  These studies were confirmed by a large cohort study. They provide an important advance that may allow “personalization” of the new aspirin recommendations.

Guest Author

Greg Cooper, MD
Co-Leader, Cancer Prevention, Control & Population Research Program
gxc12@case.edu