Less Frequent Colonoscopy After Polyp Removal Could Be the Way to Go, Study Suggests

Surveillance colonoscopy beginning 5 years after removal of high-risk adenomas is just as effective for detecting colorectal cancer (CRC) as a shorter 3-year interval, an interim analysis of an ongoing noninferiority trial showed.

The cumulative incidence of CRC at 5.5 years of follow-up was 0.77% in patients who began colonoscopy at 5 years after polyp removal versus 0.82% in the 3-year group.

The upper boundary of the one-sided 99.12% confidence interval for the between-group difference was 0.68, which met the prespecified noninferiority margin of 0.7 percentage points, reported Michael Bretthauer, MD, PhD, of the University of Oslo in Norway, and colleagues in the New England Journal of Medicine.

Moreover, the incidence of early- or late-stage CRC did not appear to differ substantially between the groups, and death from CRC was rare in both groups — three patients in the 5-year group and two patients in the 3-year group.

“More than 99% of the patients in this trial did not receive a diagnosis of colorectal cancer within 5 years after polyp removal,” the authors wrote. “This finding may trigger a discussion of the categorization of these patients as being at high risk for colorectal cancer.”

In an accompanying editorial, Aasma Shaukat, MD, MPH, of the NYU Grossman School of Medicine in New York City, and Theodore R. Levin, MD, of the Kaiser Permanente Division of Research in Pleasanton, California, noted that “for decades, surveillance after adenoma removal has been guided by a reasonable instinct: more vigilance must be better.”

This “trial offers an important corrective,” they wrote.

Whether the trial’s findings will persist through 10 years — the planned primary endpoint — is unclear, they added. “But these interim findings make one point clear already: surveillance policy must be determined not by habit or by fear of doing too little, but by evidence of what benefits patients.”

Bretthauer and colleagues noted that U.S. guidelines, as well as international guidelines, recommend frequent surveillance colonoscopies (with the first at 3 years after polyp removal) for patients with high-risk adenomas (defined as one or more adenoma with a diameter of ≥10 mm, high-grade dysplasia, or a villous growth pattern, or 3 to 10 adenomas of any kind).

“However, the recommended intervals for surveillance are based on data from observational studies and two small, randomized trials with imprecise estimates, and the guidelines emphasize the need for long-term, high-quality, randomized trials,” they wrote.

This need is important considering surveillance colonoscopy is expensive, invasive, and comes with a risk of adverse events and complications, they pointed out. “Longer surveillance intervals should therefore improve cost-effectiveness and reduce the burden on patients. However, whether longer intervals are noninferior to the currently recommended intervals for the prevention of future colorectal cancer is uncertain.”

In the ongoing European Polyp Surveillance II trial conducted in eight countries, 5,398 patients were assigned to the 5-year group and 5,401 to the 3-year group. The main indication for the colonoscopy at enrollment was CRC screening (primary colonoscopy screening or colonoscopy after a positive fecal immunochemical test), followed by clinical symptoms.

More frequent surveillance did result in the detection of more advanced adenomas of any kind, with a between-group difference of 3.5 points.

Bretthauer and colleagues suggested that this was “probably” due to some adenomas being missed in a single colonoscopy. “Whether the higher level of detection is beneficial for patients remains to be seen,” they noted, adding that the between-group difference was small, and that even advanced adenomas grow slowly.

“Clinically significant lesions that are missed until the 10-year follow-up are still likely to be identified before malignant transformation,” they wrote. “Our findings with regard to the stage of colorectal cancer at diagnosis after 5 years of follow-up suggest that detection at 10 years may be early enough to prevent advanced-stage cancer.”

The total burden of colonoscopy (the number of colonoscopies performed between enrollment and the end of follow-up) was 4,434 in the 5-year group and 8,614 in the 3-year group. Thus, 4,180 (48.5%) fewer colonoscopies were performed in the 5-year group versus the 3-year group.

“Such a decrease in the number of surveillance colonoscopies would translate into a lower patient burden, lower procedural risk, and greater availability of colonoscopy for other indications,” Shaukat and Levin noted in their editorial.

However, caution is warranted, pending the analysis at 10 years, they wrote. “Longer follow-up regarding cancers, late-stage diagnoses, and death from colorectal cancer will increase confidence in the results.”