Commentary: Further benefits to consider of noninvasive colon cancer screening

This guest commentary from Karen Simon, MD, of the Ventura County Gastroenterology Medical Group , responds to the recent cover story in Healio Gastroenterology and Liver Disease on noninvasive colorectal cancer screening options, and provides additional perspective on the benefits of Cologuard (FIT-fecal DNA test; Exact Sciences).

Colorectal cancer screening rates in the U.S. continue to be frustratingly low. While rates are demonstrating an upward trend, a significant percentage of screening eligible individuals — nearly one-third of Americans — are still not up-to-date with recommended screening guidelines, and that is prior to the lowering of the recommended age released by the American Cancer Society last week.

Initiatives and public awareness campaigns such as the National Colorectal Cancer Roundtable’s goal of screening 80% are making a difference, but we must do more if we are to achieve that goal.

The February 2018 cover story in Healio Gastroenterology and Liver Disease effectively raised awareness about noninvasive CRC screening options that are helping to move the needle. I commend the physicians involved on highlighting the importance of noninvasive options in boosting CRC screening rates. The accompanying editorial by my colleague, Edward V. Loftus Jr., MD, also served to emphasize the importance of offering a “menu for success” in increasing CRC screening rates in the U.S. In this commentary, I would like to offer an additional perspective and some clarifications.

Equal standing vs. tiered ranking

The United States Preventive Services Task Force (USPSTF) last updated its CRC screening recommendation statement in 2016, and in a departure from earlier recommendations, it granted an equal rating to seven different screening methods. In a bold statement, it concluded that for all adults age 50 to 75 years, “the best test is the one that gets done.” The USPSTF guideline recommended seven different methods that include colonoscopy, flexible sigmoidoscopy, CT colonography, fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), FIT combined with flexible sigmoidoscopy, and the multitarget stool DNA test.

The USPSTF guidelines contrast the U.S. Multi-Society Task Force (MSTF) CRC screening recommendations cited by David A. Johnson, MD, in the February article about noninvasive CRC screening options.The MSTF guidelines offer a three-tiered ranking system that recommend sequential offering of methods, with colonoscopy being offered first.

Unfortunately, this may confuse health care providers and possibly deter patients who are reluctant to get screened with an invasive test from considering all noninvasive options. From my experience, the multitarget stool DNA test (Cologuard, Exact Sciences Corporation), ranked as a second-tier test by the MSTF, warrants re-examination. It should be considered equivalent as a noninvasive screening test and, in fact, a first-choice option for all patients over 50 years old, at average risk of CRC, who are due for screening.

In my opinion, Cologuard is an effective, highly sensitive, noninvasive CRC screening option that is helping to raise CRC screening rates. More than one million individuals around the U.S. have now been screened for CRC with the Cologuard test. Most compelling is the fact that nearly half of all Cologuard users to date report they had not been screened before. Clearly this option is capturing a population of screening-eligible individuals that may have been resistant to other screening options and were in danger of avoiding screening altogether.

FIT vs. Cologuard

While the February article discusses the effectiveness of FIT, the only MSTF-ranked first-tier, noninvasive screening option, it is important to me to highlight the difference in performance between FIT and Cologuard. In a 10,000-patient, multi-site, prospective study directly comparing FIT and Cologuard performance, the manufacturer of Cologuard demonstrated an overall 92% sensitivity for all stages of CRC (essentially on par with colonoscopy’s detection rates) compared to FIT’s 74% sensitivity. Thomas F. Imperiale, MD, pointed out other benefits of Cologuard over FIT including its recommended 3-year testing interval (compared to FIT’s annual interval). Seth A. Gross, MD, FACG, also emphasized that Cologuard is better than FIT at identifying advanced adenomas and sessile serrated polyps, a critical consideration when comparing noninvasive CRC screening options. The clinical superiority of Cologuard is achieved through the design of the test and its multi-marker approach. Like FIT, Cologuard detects hemoglobin in a stool sample, but it also detects nine distinct DNA alterations in stool samples that are associated with CRC and precancer.

The February review of noninvasive CRC screening options raises questions about the cost effectiveness of Cologuard compared with FIT — another reason for the tiering decision by the MSTF. Since the MSTF reviewed the existing evidence and availability of the test, prior to publishing its recommendations in 2017, coverage of Cologuard by payers has increased substantially. The test is significantly more accessible to commercially insured individuals with minimal to no out-of-pocket costs. As reported, as of February 2018, Cologuard was covered by CMS for Medicare beneficiaries with no out-of-pocket costs and many major payers including UnitedHealthcare, Aetna, Humana and TRICARE. Since then, Blue Cross Blue Shield of Illinois, among other leading commercial insurers, now cover Cologuard, bringing coverage to nearly 90% of eligible patients.

Initial skepticism

As a gastroenterologist, I initially questioned the clinical utility of Cologuard given that a positive result requires a follow up diagnostic colonoscopy which can incur additional cost-sharing to patients. However, as a front-line screening test sensitive enough to detect CRC at its earliest, pre-symptomatic stage, it provides tremendous potential cost benefit. Early-stage CRC is easier and less costly to treat. Cologuard is cost effective in its ability to detect early, curable-stage CRC in patients resistant to colonoscopy or other invasive screening tests whose cancer may have otherwise gone undetected.

The concerns raised by the MSTF and other clinical guidelines about the specificity of Cologuard compared with FIT (87% vs. 95%, respectively) are also worthy of commentary. False positive results generated by the Cologuard test’s ability to detect the presence of blood and/or DNA alterations in stool should be considered beneficial, rather than a reason for steering patients away from using the test.

Ultimately, more patients undergo a diagnostic colonoscopy who might otherwise have skipped screening altogether. Recent published studies demonstrating this effect, as well as another study that demonstrated increased diagnostic colonoscopy yield in patients presenting with a positive Cologuard test, highlight the clinical practicality and use of the test.

I commend my colleague Dr. Loftus for his recent editorial and its underlying message urging gastroenterologists like myself to offer alternative CRC screening options to their patients. Only by offering a varied menu of screening choices will we be successful in convincing more patients to get screened for CRC and ultimately reach the 80% goal. We share in this mission of reducing the pain and suffering caused by a cancer that remains “the most preventable, yet least prevented” afflicting our population.

References:

American Cancer Society, Cancer Facts & Figures 2018; https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2018.html.

Exact Sciences press release, February 26, 2018; http://investor.exactsciences.com/investor-relations/press-releases/press-release-details/2018/More-than-1-Million-Screened-for-Colorectal-Cancer-with-Cologuard/default.aspx.

Exact Sciences Laboratories data, Patient Satisfaction Survey, May-Dec 2017; n=3772.

Imperiale TF. N Engl J Med. 2014;370(14):1287-1297.

Itzkowitz SH. J Natl Cancer Inst. 2009;101(18):1225-1227.

Johnson DH. Gastrointest Endosc. 2017;85(3):657-665.

Prince M. World J Gastroenterol. 2017;23(3):464-471.

Rex DK. Gastroenterol. 2017;153(1):307-323.

US Preventive Services Task Force. JAMA 2016;315(23):2564-2575.

For more information:

Karen Simon, MD

Ventura County Gastroenterology Medical Group

2241 Wankel Way, Suite A

Oxnard, CA 93030

Disclosure: Simon reports a consulting relationship with Exact Sciences.