CRC Screening: 45 Is the New 50, and 85 Is the New 75

Build a better mousetrap, and the world will beat a path to your door. Find an accurate, completely noninvasive method for colorectal cancer screening and you’ll probably win the Nobel Prize for Medicine or Physiology.

But until then, we’ll have to make do with colonoscopy, fecal immunochemical testing (FIT), and other messy but necessary means for preventing full-blown CRC and reducing the risk of CRC morbidity and mortality. And start turning to them earlier in patients’ lives.

The US Preventive Services Task Force (USPSTF) has issued an update of its 2016 recommendations for CRC screening, for the first time advising that screening for all average-risk adults begin at age 45. This new recommendation is in line with the guidelines issued by the American Cancer Society, which were updated in 2018, to reflect the inescapable truth that CRC is increasingly being diagnosed at a younger age.

Not to be left out, the US Multi-Society Task Force (MSTF) — which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy — issued a statement supporting lowering the age of initial screening in normal-risk adults to 45, and promised that an update of their 2017 guidelines would include the new recommendation.

Recommendations Influence Reimbursement

Guidelines are often honored as much in the breach as in the observance, but those issued by the USPSTF have unique sway, according to Sonia S. Kupfer, MD, from the section of gastroenterology, hepatology, and nutrition in the Pritzker School of Medicine at the University of Chicago, and colleagues.

“While other guidelines have recommended this younger age, the USPSTF guidelines directly inform insurance coverage and waiving of cost sharing as part of federal law,” they write in an editorial accompanying the USPSTF guideline statement in the Journal of the American Medical Association.

Although the USPSTF rated its recommendation on starting at age 45, a ‘B’ level — indicating a moderate certainty of moderate benefit — it’s an important step, Kupfer said in an interview with Medscape Medical News.

“The big advantage here is that we may be able to make a dent in this early-onset colorectal cancer, which, having seen many of these patients, is very alarming, and they don’t always seem to have classic risk factors,” she said. “So, getting them when we can potentially prevent cancer by taking out polyps, or even getting them in an earlier stage, certainly will be beneficial.”

The MSTF also considered recommending 45 as the starting age for normal-risk patients in its 2017 guidelines, noted Douglas Rex, MD, who was chair of the committee that drew up those guidelines, as well as director of endoscopy at Indiana University Hospital in Indianapolis.

“Since that time there has been more evidence, and there’s also some empiric evidence about the yield of screening in the 45- to 49-year-old age group,” he said in an interview.

The One That Gets Done

Although the various guidelines differ in specifics, all are in agreement on the general proposition that colonoscopy is the gold standard for screening and detecting the presence of polyps, adenomas, and CRC.

But as USPSTF member Martha Kubik, PhD, RN, director of the George Mason University School of Nursing in Fairfax, Virginia, said in a statement: “The right test is the one that gets done.”

Gastroenterologists acknowledge that despite its efficacy, colonoscopy is an invasive procedure involving meticulous and unpleasant and/or uncomfortable bowel prep, sedation, and significant time requirements. 

In the theory that something is better than nothing, with clinical evidence of varying degrees of quality, the USPSTF recommends the following procedures or tests for average-risk adults:

• Colonoscopy screening every 10 years

• Flexible sigmoidoscopy every 10 years plus annual FIT

• CT colonography every 5 years

• High-sensitivity guaiac fecal occult blood test (gFOBT; Hemoccult II) or FIT every year

• Stool DNA-FIT (Cologuard) every 1 to 3 years

The US Food and Drug Administration also recently approved an artificial intelligence device designed for use with an endoscope, which its manufacturer says can help clinicians detect gastrointestinal lesions they might otherwise miss. This is not a new screening method, but rather an enhancement of existing ones. It neither diagnoses lesions nor recommends treatments, and is not intended to take the place of laboratory sampling.

“I think artificial intelligence is poised to make colonoscopy more effective,” Rex said. “In the first five trials that we’ve seen, the average increase in the adenoma detection rate has been 11%, and for each 1% gain in the adenoma detection rate, patients have about a 3% decline in their risk of getting cancer after a colonoscopy and about a 5% decline in their risk for fatal cancer. Those are the largest gains that we’ve seen from a technology.”

Different Evidence, Varied Outcomes

Despite the recommendations, a quick dive into the morass of evidence from multiple studies featured in the updated USPSTF guidelines shows that not all screening methods are created equal.

A single colonoscopy, for example, has been shown in large cohort studies to be associated with a 68% reduction in CRC mortality vs no screening, compared with a 26% reduction with flexible sigmoidoscopy performed every 3-5 years, 22% reduction with Hemoccult II, and 10% with FIT every 2 years.

The USPSTF investigators did not find any studies evaluating the effectiveness of CT colonography, high-sensitivity gFOBT, stool DNA with or without FIT, or serum tests on CRC incidence, CRC mortality, or both.

The two visualization methods for which studies were available, colonoscopy and CRC colonography, were generally comparable in sensitivity and specificity for detecting and correctly identifying adenomas 6 mm and larger, although colonography had higher sensitivity for CRC than colonoscopy.

When performed in two to nine annual or biennial rounds, gFOBT was associated with a reduction of CRC-specific mortality of 9% after 19.5 years and 22% at 30 years, as compared with no screening.

In observational studies, screening colonoscopy and FIT were both associated with lower risk of CRC incidence or mortality, compared with no screening.

When to Stop?

The major guidelines are all in agreement that once an individual reaches age 75, the decision about whether to continue screening should be made on a case-by-case basis, depending on the patient’s overall health, relative risks, and life expectancy.

But if a study published 2 days after the release of the USPSTF guidelines is any indication, just as 45 is the new 50 for starting screening, 85 may be the new 75 for stopping it.

As researchers from the Massachusetts General Hospital Cancer Center in Boston reported in JAMA Oncology, screening endoscopy for persons older than 75 in otherwise good health can reduce the risk for CRC incidence and CRC-related death by approximately 40%.

The researchers also found, however, that screening did not provide a significant survival benefit for individuals older than 75 with cardiovascular disease, diabetes, or 3 or more other health conditions.

“Until now, there really weren’t clear data to help us decide whether patients should be screened after age 75,” said co-investigator Andrew T. Chan. MD, MPH, a gastroenterologist and chief of the clinical and translational epidemiology unit at Mass General, in a statement. “Current guidance was largely based on modeling and extrapolation of studies conducted in other age groups, and not on solid data to show whether screening was actually helpful in an older population.”

In an interview, Chan said that while the recommendation to screen older adults has to be tailored to individual risk factors, “it should help to provide more confidence for clinicians and patients.”

“I think this is particularly important, because we know that the population as a whole is aging, so more and more people are in this category of over the age of 75, and it’s not an infrequent issue in the clinic as to what to continue with respect to preventative interventions,” he said.

Kupfer said that the findings by Chan and colleagues are largely in keeping with guideline recommendations.

“We factor in a lot of different things, including comorbidities, in making the decision to continue screening up to age 85. Certainly, physiological age and chronological age aren’t always the same, so not every 75-year-old is going to be in the same boat,” she said.

“The risk goes up as people get older, but there starts to be competing mortality at some point, and if you have to do a colonoscopy there are obviously issues related to sedation that, as someone gets older, we have to take into consideration,” she added.

Patients frequently confuse screening with surveillance, Rex said, and he has had patients tell him: “I hear you don’t do these anymore on people over the age of 75.”

“But that’s not true,” Rex emphasized.

“Screening is generally considered appropriate even up to the age of 85, but between 75 and 85 it should be considered on an individual basis, and there are several considerations there,” Rex said. “One is whether a patient has ever been screened before. The second is how they were screened. Third is their life expectancy and how many comorbidities they have. And fourth is their personal feelings about it and interest in it.”

He pointed out that the false-positive rate of stool DNA-FIT tests increases with age, and that for older patients who were previously screened, a standard FIT test may be a more appropriate.

So Doc, What Should I Do?

Multiple guidelines, levels of evidence, different screening methods with varying efficacy individual risk factors — how can clinicians make sense of all these data at the practice level?

“Any modality can be used for screening. Colorectal cancer screening can be done in a number of different ways, and I think that sometimes gets lost in the shuffle, and the thought becomes that everybody has to get a colonoscopy at 45, but there are certainly other tests,” Kupfer said.

“This just reminds us that we should be thinking about ways we can be doing screening on a population basis, so that we make sure there is equity,” she said.

It’s also important to remember that patients with familial CRC syndromes should begin screening at an even earlier age than average-risk adults, she emphasized.

“To really make a dent in early-onset colorectal cancer, we have to continue to take an active case-finding approach,” she said.

Rex noted that despite minor differences, the major guidelines are all similar in their initial statements that screening works.

“We’ve still got 50,000 people a year dying from colorectal cancer, lots more than that of new cases,” he said. “If you look at a single factor contributing to that the most, it’s that a lot of the American public is not getting screened at all — it can be up to 40% of the population, depending on what state you’re in.”

Although there are a variety of screening methods available, there are few studies directly comparing them, leaving clinicians at the practice level with the task of presenting all or some of them to patients.

“What the Multi-Society Task Force says that is different, and I think that they get right, is that we don’t have any data [indicating] that offering five, six, or seven options increases the chance of screening — there’s really no evidence that going past two does,” Rex said.

“The list of options also includes things that nobody actually does,” he added. “For example, flexible sigmoidoscopy has dropped off the map, and FIT has largely replaced guaiac-based testing, even high-sensitivity guaiac. Nobody is really doing CT colonography. The three tests that are being used are colonoscopy, FIT, and [stool DNA-FIT].”

Rex said that he favors sequential offers, presenting colonoscopy first, emphasizing the benefits for higher-risk patients, and if the patients refuse, offering a fecal-based test.

“Minimizing the number of options makes the conversation feasible, and it’s still very responsible,” he said.

Kupfer has performed collaborative research with Myriad Genetic Laboratories, Inc. She is an editorial advisory board member for GI & Hepatology News from MDedge, part of the Medscape Professional Network. Rex serve(d) as a consultant for Olympus Corporation; Boston Scientific; Medtronic; and Aries; and received research support from EndoAid; Olympus Corporation; and Medivators. He has ownership in ai4gi. He is an editorial board member for Medscape Gastroenterology. Chan has served as a consultant to Pfizer, Bayer AG, and Boehringer Ingelheim.

JAMA. Published online May 18, 2021. Full text

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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