Another Look
By Beth W. Orenstein
Radiology Today
Vol. 22 No. 7 P. 14

Why the USPSTF Recognizing CTC for Screening Is Good News for Colon Cancer Prevention

Most types of colorectal cancer begin as adenomatous polyps—glandlike growths on the mucous membrane that lines the large intestine. They typically take several years to develop. Early detection and removal of these precancerous polyps can reduce the incidence and mortality of colorectal cancer.

While colon cancer is highly treatable and one of the more curable cancers if detected in its early stages, more than 52,900 people in the United States are expected to die from it this year, according to the US Preventive Services Task Force (USPSTF). Colon cancer is most frequently diagnosed in people aged 65 to 74. However, 10.5% of new colorectal cancer cases occur in those younger than 50, and the incidence of colon cancer is on the rise, according to a report in the May 2021 issue of the Journal of the American Medical Association. The death of actor Chadwick Boseman at 43 from colon cancer in August 2020 helped shine a light on the dangers of undetected disease in younger adults.

In May, the USPSTF updated its 2016 recommendations for screening for colorectal cancer. The task force reviews its recommendations about every five years to make sure that they reflect the latest research. With new research showing that colon cancer is on the rise in younger adults and that screening is effective and can be lifesaving, the task force was able to expand its screening recommendations to include people aged 45 to 49. Previously, the USPSTF had recommended screening for colorectal cancer in all adults aged 50 to 75.

The USPSTF recommendations “mean that payers will need to reimburse for screening in younger patients,” says Judy Yee, MD, FACR, university chair of radiology at Montefiore, a professor of radiology at Albert Einstein College of Medicine in New York, and chair of the ACR Colon Cancer Committee. Yee notes that the updated USPSTF recommendations parallel those of the American Cancer Society (ACS), helping to make the guidelines more uniform and less confusing for patients, providers, and payers.

The updated guidelines for colon cancer screening include CT colonography (CTC), also known as virtual colonoscopy, every five years. Significantly, both the USPSTF and the ACS now recognize CTC as a valid test option for colorectal cancer screening. CTC is a less invasive test than optical colonoscopy and “is a great option for those patients who otherwise would remain unscreened,” Yee says. CTC is also indicated for patients who are unwilling to undergo the more invasive optical colonoscopy or have contraindications for colonoscopy. Contraindications for colonoscopy include those who are frail with multiple comorbidities or who have a sedation risk, those on anticoagulation therapy, and those who have failed colonoscopy, Yee says.

Best Noninvasive Screening
An advantage to CTC for colorectal cancer screening is that it is noninvasive. “There’s no need for sedation, so patients don’t have to have someone else accompany them to the procedure or drive them home,” Yee says. Perhaps, having to arrange transportation is a minor inconvenience for most people, “but it could be particularly pertinent during and after the COVID-19 pandemic,” she adds.

Stool-based exams, such as the fecal immunochemical test (FIT), which uses antibodies to detect blood in the stool, and the FIT-DNA test, which combines the FIT with a test that detects altered DNA in the stool, are also noninvasive. However, they are only able to detect cancer and not the precursor polyp, Yee says. “Cancer prevention requires reliable detection of large, precancerous polyps—and CTC is the only noninvasive test that provides this,” she says.

Perry J. Pickhardt, MD, a professor of radiology, chief of gastrointestinal imaging, and medical director of cancer imaging at the University of Wisconsin School of Medicine & Public Health in Madison, is the lead author of a systematic meta-analysis comparing the diagnostic performance of noninvasive colorectal cancer screening tests published earlier this year in the American Journal of Roentgenology. The study found that colorectal cancer prevention was highest with CTC, followed by multitarget stool-DNA, and lowest with FIT, with an emphasis on the comparison of positive predictive value and detection rate for advanced neoplasia. The researchers limited their search to screening studies in asymptomatic adults and excluded studies with symptomatic patients or high-risk groups, such as patients with inflammatory bowel disease, hereditary nonpolyposis colorectal cancer, or familial adenomatous polyposis.

“The only other way to offer this level of colorectal cancer prevention comparable to CTC is to undergo full/invasive optical colonoscopy,” Pickhardt says. However, he explains, optical colonoscopy is “more expensive, more inconvenient, and riskier” than CTC. Because only 5% to 10% of older adults will harbor a large polyp, the vast majority of people do not require an invasive colonoscopy, Pickhardt says.

Tricky Comparisons
Colon cancer is seen in only about 1 in 500 screening individuals, and all of the approved screening tests will detect most of these cancers, although CTC and colonoscopy are somewhat better than the stool-based tests, Pickhardt says. Stool-based tests also have a higher false-positive rate, which ultimately leads to more unnecessary colonoscopies—although that number is still many fewer than if everyone were screened with colonoscopy to start, he says.

Yee says it is difficult to tell how false-positive rates compare in CTC and colonoscopy. “It’s hard to say whether the lesion shown by CTC and not confirmed by colonoscopy really constitutes a false-positive result,” she says. “Of course, this may be the case, but there is also a possibility that the lesion was not detected during colonoscopy or was assessed as a lesion of a different size or location.”

The USPSTF recommends a five-year interval for initial CTC screening. Pickhardt agrees with this recommendation. However, he says, if an individual has a second negative CTC exam after five years, “we recommend that they can wait up to 10 years before repeating.”

Like colonoscopy, CTC still requires bowel cleaning. But having to cleanse the bowel may be its biggest disadvantage, Yee says. Also, if the CTC has a significant finding, the patient is likely to be referred to colonoscopy for biopsy or polypectomy. Fortunately, Yee notes, the number of patients who must be referred for colonoscopy because of positive CTC findings is small.

If precancerous polyps are found on CTC, patients likely will need to undergo a visual colonoscopy and, thus, will have to prep again. Pickhardt has two answers to the many who bring up this argument against CTC: One is that in some screening centers, if a large polyp or cancer is detected with CTC, patients can go on to same-day colonoscopy without the need to re-prep. Also, he says, because less than 10% of individuals who are screened will have a large polyp at risk for cancer progression, 90% would therefore avoid the more invasive and expensive test. Besides, Pickhardt says, over the years, the CTC bowel prep has become easier (lower volume and less intense).

Radiation dose associated with CTC screening also has been lowered considerably and is not a realistic safety concern, Pickhardt says. A study published in Academic Radiology in May 2021 found that applying spectral filtration and advanced modeled iterative reconstruction techniques in third-generation dual-source CT provides an alternative low-dose CTC strategy that could be feasible in clinical colorectal cancer screening or diagnostic scenarios. Yee says dual-energy CT technology is being evaluated for improved electronic cleansing with decreased artifacts. “This could potentially aid in decreasing the bowel cleansing requirements for CTC,” she says.

Some insurers will consider a follow-up colonoscopy triggered by a potentially positive CTC to be diagnostic and no longer classified as a screening test. Because of the change from preventive to diagnostic, some insurers may no longer cover CTC in full. Yee recommends that patients check their coverage with their insurance companies about whether they will be covered if they undergo a CTC and subsequently require a colonoscopy. That way, they will not be surprised with a bill for the deductible and copay, she says. And if they do undergo CTC followed by a colonoscopy and are billed afterward, “they can always appeal the insurance company’s decision,” Yee says.

Differentiating Factors
Another issue with CTC is that it does not differentiate definitively between benign and premalignant colorectal polyps, which is crucial for individual risk stratification and therapy guidance. Yee says AI is being evaluated for use in colon cancer screening with CTC and that it shows promise. “Areas of investigation include the use of AI for lesion detection, such as for sessile serrated lesions, lesion characterization of benign vs malignant lesion, and automated segmentation of extracolonic findings,” she says.

A machine learning algorithm could be the answer to this issue, according to a proof-of-concept study published in May 2021 in the journal Radiology. “Adding machine learning to CTC promises a more precise selection of patients who would profit from subsequent endoscopic polypectomy,” study lead author Sergio Grosu, MD, a radiologist from University Hospital, Ludwig Maximilian University of Munich in Germany. Grosu says his team’s study used radiomics-based image analysis and found that it enabled noninvasive differentiation of benign and premalignant CTC-detected colorectal polyps with an area under the operating characteristic curve of 0.91, sensitivity of 82%, and specificity of 85%. In two subgroup analyses of the external test set, the area under the receiver operating characteristic curve was 0.87 in the size category of 6 to 9 mm and 0.9 in the size category of 10 mm or larger, the study found.

“Our initial results were surprisingly good,” Grosu says. However, he says, “further studies with larger numbers of participants and prospective settings are needed to make a reliable and consistent statement.”

To perform the study, the researchers leveraged the power of radiomics, a process of extracting quantitative features from medical images, to characterize polyps beyond what was apparent to the naked eye. They developed a machine learning algorithm to predict the character of the individual polyps based on quantitative image features extracted through radiomics. They applied the noninvasive, radiomics-based machine learning method on CTC images from a group of asymptomatic patients at average risk of colorectal cancer. The machine learning algorithm was trained on a set of more than 100 colorectal polyps in 63 patients and then tested on a set of 77 polyps in 59 patients.

Additional studies with larger samples and prospective settings needed to validate the research team’s findings, and further refinement of the machine learning–based image analysis is also necessary, Grosu says. Refining machine learning–based image analysis is necessary to “achieve higher precision in polyp differentiation as well as workflow optimization for better applicability in clinical routine,” he says.

— Beth W. Orenstein of Northampton, Pennsylvania, is a freelance medical writer and regular contributor to Radiology Today.