Experts debate dilemmas in colorectal cancer screening

Most medical decisions require weighing risks and benefits, but colorectal cancer (CRC) screening poses more than the usual amount of challenge on this front.

"Screening recommendations vary considerably across the globe, and even among organizations within the United States," said Christine Laine, MD, MPH, FACP, noting that ACP added to the debate in August 2023, offering a guidance statement on screening average-risk patients that was published by Annals of Internal Medicine.

To help clinicians sift through the competing recommendations, Dr. Laine, Editor-in-Chief of Annals and a Senior Vice President at ACP, led off the latest ACP/Annals forum, "Controversies in Colorectal Cancer Screening." .

"We've assembled an astute panel of experts to discuss this controversy, clarify the rationale supporting the varying recommendations, and hopefully better equip physicians to help individual patients make colorectal cancer screening choices that best align with patients' clinical situation, values, and preferences," said Dr. Laine.

The forum panelists responded to screening vignettes posed by moderator Ana María López, MD, MPH, MACP, professor of medical oncology at Jefferson University in Philadelphia. The first vignette—a healthy 45-year-old with no risk factors coming in for a regular visit—focused squarely on ACP's latest guidance statement.

"The new American College of Physicians recommendations say clinicians should consider not screening asymptomatic average-risk adults between the ages of 45 and 49 years," said panelist Carolyn Janet Crandall, MD, MS, MACP, Chair of the College's Clinical Guidelines Committee and a professor of medicine at the University of California, Los Angeles.

That guidance is based on the evidence that screening offers little benefit, she explained. "Screening at age 45 instead of 50 would be expected to yield somewhere between eight to 10 additional life-days per person. It translates to about a 0.1% reduction in colorectal cancers and a 0.04% reduction in colorectal cancer mortality."

Dr. Crandall noted that she wouldn't even raise the issue of CRC screening in this case if the patient didn't, sparking the first difference of opinion among the panelists. Carol A. Burke, MD, FACP, disagreed. "As a gastroenterologist, my preference would be to discuss preferences with this patient," she said. "I know he didn't bring it up. … Part of my job is to ensure that patients get on the bandwagon."

Although the hypothetical patient is at low CRC risk right now, the trends in those just older than he is create cause for concern, according to Dr. Burke, a gastroenterologist at the Cleveland Clinic in Ohio and an international expert on polyposis syndromes.

"Unfortunately, what we've seen over time is that individuals between the ages of 50 to 55 have a slight uptick in colorectal cancer and a decrease in screening," she said. "So I like to talk to people about it and say, 'Here are the facts, here's the epidemiology that we're seeing in this birth cohort.'"

If the patient opted for screening, she'd recommend fecal immunochemical testing (FIT). If not, she'd educate about what symptoms should merit a return visit. "I wouldn't be offering colonoscopy necessarily to an individual at very low risk at a young age. We just don't have the resources to accomplish it," Dr. Burke said.

Michael Bretthauer, MD, PhD, brought the international perspective into the debate. "I don't think that any European country recommends screening below the age of 50," he said. "The risk is just too small."

The typical mechanism of screening is another difference across the continents, added Dr. Bretthauer, a gastroenterologist and professor of medicine at the University of Oslo in Norway and an Associate Editor of Annals. "Almost all [European] countries use fecal testing and not colonoscopy as the primary screening test, with a few exceptions."

The panelists moved on to a second vignette, which posed the opposite screening dilemma—a 70-year-old woman with several serious comorbidities, including three heart failure exacerbations in the past year, who has never undergone CRC screening. Should she now?

"Don't even discuss it," said Dr. Burke. "With these multiple life-threatening comorbidities, as well as recent hospitalizations, she probably doesn't even have a life expectancy of more than five years, let alone more than 10 years." The protective benefits of colonoscopy are seen over 10 to 15 years, she noted.

In addition to lower benefit, the patient also faces higher risks. "I am concerned that colonoscopy can be associated with adverse events that would impact the quality of her life," said Dr. Burke. "The risk of colonoscopy increases from 2% to 4% to about 11% by age groups 75 to 85 and 85 and over."

Choosing a test other than colonoscopy doesn't solve that problem, noted Dr. Bretthauer. "It's a slippery slope even for fecal testing here, because then what would you do when you get that positive test? This patient, from her comorbidities, probably is on an anticoagulant, which gives you additional problems, because there is a higher probability that the FIT is false positive."

The biggest challenge in this scenario may not be coming up with a recommendation, but communicating it to patients and families, the panelists agreed. Dr. Burke described the response she sometimes receives when she recommends that a patient should stop screening. "Their sons say, 'Are you sending my family member home to die? Why would you tell my mother that now?' Because there is an overestimation by loved ones as well as patients."

She noted that more detailed risk prediction tools are needed to really solve this problem but suggested using the data that are available to carefully explain the balance of risks and benefits. "You're really bringing to the fore the importance of really sitting with a patient going through what are the risks," agreed Dr. López.

The third vignette offered a less common scenario: A 40-year-old woman whose brother was diagnosed with colon cancer at age 46 years and who is wondering if she should start screening. Dr. Bretthauer offered a simple way to think about patients like this.

"Rule of thumb in this situation is that you take the age of the index case and you subtract 10 years. So he was 46, the sister is now 40, … so about now, she's a little late [starting screening] actually," he said. "I would definitely choose colonoscopy for this patient."

Dr. Burke didn't disagree but also suggested a much higher-tech decision-making method. "Her brother should have had tumor testing to look for evidence of microsatellite instability," she said. "It's a screening test for Lynch syndrome and some of the other pathogenic variants."

Such DNA testing is now widespread in the U.S., she noted, and if for some reason the brother doesn't undergo it, the patient can do some DNA testing of her own. "Then the patient should be counseled by a genetics expert and have panel testing for the pathogenic variants that would be associated with colorectal cancer, because that changes the whole ballgame if she has something."

DNA testing is much less expensive than it used to be and should be covered by insurance for this patient, Dr. Burke noted. "It includes the most common polyposis-related genes, as well as the ones that occur less than 1% of the time."

While it may be appropriate for this patient to undergo DNA testing of her blood or saliva, stool DNA testing is not a good fit for anyone whose risk comes from a family history, noted the experts, who all agreed on colonoscopy as the right test in such cases.

"That multitarget stool DNA test is not FDA-approved for high-risk individuals," said Dr. Crandall. "Fecal immunochemical testing, again, is an average-risk test."

She went on to describe her reservations about stool DNA testing for any patient. "In the latest version of the recommendations from the American College of Physicians, we observed that no randomized clinical trials that were included in the systematic review have evaluated the efficacy of stool DNA testing," said Dr. Crandall.

Dr. Bretthauer doesn't expect any to be forthcoming, either. "I don't think the companies are interested in sponsoring such trials," he said. "I think the DNA test which is on the market now is not really that much better than a FIT test and the FIT test is so much cheaper, which I think should be taken into consideration, at least on a [societal] level."

Limitations of stool DNA include that results come back simply positive or negative, without any adjustable threshold, and that it's uncertain how often testing needs to be repeated, Dr. Bretthauer added. "The company says every three years, but there's no data for that."

Clinicians are likely to be faced with yet another screening option before long. "The new RNA test, which I predict will be on the market soon, is fairly similar in performance to the DNA test that we currently have," Dr. Bretthauer said.

Testing frequency is an important issue in judging the cost-effectiveness of new testing options, said Dr. Crandall. "It isn't just the single one, right? It's over a 10-year window, and sometimes with these newer, more expensive tests, it actually will add up to more than a single colonoscopy, depending on the interval."

Finally, the panelists circled back to the issue that drove the ACP guidance—when to start screening average-risk patients. "It's really challenging," said Dr. Crandall. "Our patients really want us to listen. And so if we hear their concerns, we should address them."

Patients may be alarmed by media reports of increasing CRC incidence in their age group, but she advised physicians to focus on the absolute rather than relative risk. "In average-risk person, between ages 45 and 49, we're expecting about 35 cases per 100,000," said Dr. Crandall. "Put things into perspective. … If that person really does desire a screen, then a screen can be ordered."

If not, there are likely many other medical issues that time with these patients could be spent on, she added. "Let's help take care of the blood pressure management, hypertension management, the diabetes management, things where we have proven efficacy," Dr. Crandall said.