SAN DIEGO—The 2020 guidelines for surveillance colonoscopy have steered gastroenterologists toward more appropriate surveillance intervals for their patients post-colonoscopy, but research continues to refine individual risk and recommendations, according to the guideline author, Samir Gupta, MD.

In a presentation at DDW 2025, Dr. Gupta, a professor of medicine at the University of California, San Diego, and staff physician at the Jennifer Moreno VA Medical Center, also in San Diego, provided suggestions on how surveillance should be approached today and how it might be considered in the future.

Dr. Gupta said he envisions a future of “right-sized surveillance,” based less on guidelines incorporating number, size and histology of polyps and more on intervals informed by “very high-quality colonoscopy, with excellent ADR [adenoma detection rate] and complete polyp excision, along with tools for much more precise risk stratification.”

This approach should result in a substantial low-risk group for whom 10-year surveillance intervals would be sufficient, perhaps even with periodic noninvasive surveillance, and a much smaller high-risk group in whom colonoscopy would be performed every three to five years, perhaps incorporating intensive noninvasive surveillance. “To me, this should all come with much more certainty that surveillance can reduce the risk for colon cancer,” Dr. Gupta said.

image

The Right Understanding

But it is first important to understand what it means to right-size the surveillance intervals, he said, which means having the “right understanding of the drivers of post-polypectomy risk, the right patient based on colorectal cancer risk, and the right intervention to address the particular CRC risk.”

The “right understanding” of post-polypectomy risk is related to biological factors—including demographics, genetic predisposition, comorbidities, exposures to medications, smoking and other risk factors—and to the quality of colonoscopy, as measured by bowel prep and colonoscopist skill. “Together, these two big buckets collude to drive post-polypectomy CRC risk, with quality probably the most important factor and, advantageously, the most modifiable,” Dr. Gupta noted.

A study examining 10-year cumulative risk by baseline colonoscopy findings and colonoscopist performance (=20% vs. <20% ADR) showed that better performance was associated with lower risk within each adenoma risk group (Gastroenterology 2020;158[4]:875-883). Cumulative risk after high-risk adenoma removal by a higher-performing colonoscopist was similar to that in patients with a low-risk adenoma removed by a poorer performer.

Further emphasizing this point, Dr. Gupta cited data from a national case-cohort study of U.S. veterans followed after polypectomies that found that most incident CRCs (55.2%) and fatal CRCs (39.5%) occurred within four years, before surveillance colonoscopy was due. A root cause analysis showed that 60% of these interval cancers were likely missed at polypectomy (DDW 2024, abstract 185).

“This has nothing to do with the type of polyp that was removed. It really has to do with the quality, underscoring that much of the neoplasia we see after polypectomy was probably missed or incompletely resected at baseline,” said Dr. Gupta, who led that study.

The Right Patient

Regarding the “right patient,” the guidelines recommend looking at the polyp characteristics, which means broadly characterizing patients as having no adenoma, low-risk adenoma, non-advanced serrated polyp, high-risk adenoma or advanced serrated polyp. The CRC incidence per 10,000 person-years generally is low and similar for the first three subgroups (approximately 3-4/10,000) but is significantly higher for high-risk adenoma (14/10,000) and advanced serrated polyps (21/10,000)—about a threefold increase over the patient with normal findings on colonoscopy. Similarly, the risk for CRC mortality is almost tripled in the high-risk adenoma group, Dr. Gupta said, but he noted that “even in these high-risk groups, 14 to 20 cases per 10,000 person-years are still really low rates.”

Factors besides polyp size are associated with CRC after polypectomy and should also be kept in mind, he noted, such as advanced age, male sex, smoking, physical inactivity, poor diet, metabolic syndrome, obesity and lower ADR of the colonoscopist who performed the baseline polypectomy. Polygenic risk score remains under investigation and is not yet helpful in determining risk.

“With these factors in mind, there has been a lot of interest in generating prediction models for identifying patients at risk for metachronous advanced neoplasia or colon cancer,” Dr. Gupta said. Four studies published in the last two years evaluated models that included age, polyp size, type of polyp and patient characteristics. The performance of the models was calculated as the area under the curve (AUC) or C-statistic, and these were determined to be AUCs of 0.61, 0.62 and 0.70, and a C-statistic of 0.75 for predicting either metachronous advanced neoplasia or CRC (Clin Gastroenterol Hepatol 2023;21[1]:29-32; EClinicalMedicine 2023;62:102139; Am J Gastroenterol 2024;119[8]:1590-1599; Gastro Hep Advances 2024;3[5]:671-683). All models performed better than using polyp size, histology and number, or guidelines alone, he said.

“It’s important to remember that if you treat the current guidelines as a diagnostic or predictive test, where you try to identify those people who are going to go on to have metachronous neoplasia, they’re only 56% sensitive and 57% specific for identifying those who will go on to have a high-risk polyp—barely better than flipping a coin,” he commented. “There is a lot of room for improvement.”

The Right Intervention

When it comes to the “right intervention” to address CRC risk, Dr. Gupta maintained that “surveillance colonoscopy works, but I think that we can do better.”

The main question here is the effect of surveillance colonoscopy on CRC incidence and mortality. Two large retrospective cohort studies recently reported hazard ratios for incident CRC to be 0.71 and 0.61 for high-risk polyps and 0.58 and 0.57 for low-risk polyps (Gut 2021;70[12]:2307-2320; 2024;73[10]:1675-1683). The retrospective case-cohort study previously mentioned and led by Dr. Gupta examined the effect of exposure to guideline-concordant surveillance on post-polypectomy risk and found hazard ratios of 0.21 and 0.16, respectively (DDW 2024, abstract 185).

“Colonoscopy appears to be effective for reducing post-polypectomy incident CRC, but there are some challenges and problems,” he noted. “It’s expensive, participation is suboptimal, some patients prefer alternative methods and many patients receive surveillance late. Certainly, surveillance intervals are too late to catch post-polypectomy cancers, since a large proportion occur before the patient is due for surveillance exam. The question is, what could be the solution?”

Dr. Gupta said noninvasive testing methods could be acceptable alternatives to colonoscopy, which is supported by the observational MOCCAS (Molecular stool testing for Colorectal CAncer Surveillance) study, in which 2,226 participants with post-polypectomy surveillance indications underwent a multitarget stool DNA test and two fecal immunochemical tests, OC-SENSOR (Eiken) and FOB Gold (Sentinel) (Gastroenterology 2025;168[1]:121-135). The investigators simulated stool-based strategies to fine-tune each test’s positivity threshold to yield a strategy at least as effective as colonoscopy surveillance.

Using a 6-mcg cutoff every two years, the OC-SENSOR test had a sensitivity of 71% for CRC and 37% for advanced neoplasia. Using a 185-score cutoff every three years, the multitarget stool DNA test had a sensitivity of 86% for CRC and 59% for advanced neoplasia. The number of colonoscopies was reduced by up to 41%. “This approach could achieve similar outcomes as surveillance colonoscopy, but the big advantage was that you could reduce the number of surveillance colonoscopies,” Dr. Gupta noted.

He acknowledged that these sensitivities are still suboptimal but should be viewed in the context of current approaches. “The prediction models and these noninvasive tests are likely better than current guidelines for predicting who will have advanced neoplasia or colon cancer. For this reason, I think these alternatives have the potential to reduce the burden of colonoscopy and are, therefore, worth considering.”

—Caroline Helwick

Dr. Gupta reported financial relationships with CellMax, Freenome, Geneoscopy, Guardant Health, InterVenn Bio and Universal Diagnostics.

This article is from the July 2025 print issue.