麻豆传媒

Patients with any polyp subtype had a higher risk than the general population of developing colorectal cancer (CRC) in a Swedish cohort that had generally not been previously screened, a large register-based study found -- a finding that contrasts with the general belief that individuals with non-advanced adenomas have no significantly increased risk. CRC risk rose with advanced histology for both conventional adenomas and serrated polyps.

In terms of CRC mortality, however, the risk increased only in patients with sessile serrated polyps, tubulovillous adenomas, or villous adenomas but not in those with hyperplastic polyps or tubular adenomas. "Our findings suggest that patients with any of the latter three lesions might benefit from colonoscopy surveillance," wrote Jonas F. Ludvigsson, MD, PhD, of the Karolinska Institutet in Stockholm, and colleagues.

Their study, published online in the compared 178,377 polypectomy patients and 864,831 matched individuals from the general population. Over a median follow-up of 6.6 years (interquartile range 3.0-11.6), the researchers identified 4,278 incident CRCs and 1,269 CRC deaths in the polyp cohort, and 14,350 incident CRCs and 5,242 CRC deaths in "general reference" individuals.

In terms of polyp type, the investigators found the following:

• A 10-year cumulative CRC incidence of 1.6% (95% CI 1.5%-1.7%) for hyperplastic polyps, 2.5% (95% CI 1.9%-3.3%) for sessile serrated polyps, 2.7% (95% CI 2.5%-2.9%) for tubular adenomas, 5.1% (95% CI 4.8%-5.4%) for tubulovillous adenomas, and 8.6% (95% CI 7.4%-10.1%) for villous adenomas compared with 2.1% (95% CI 2.0%-2.1%) in reference individuals

• An increased risk of CRC in polyp patients, with a multivariable hazard ratio (HR) of 1.11 (95% CI 1.02-1.22) for hyperplastic polyps, 1.77 (95% CI 1.34-2.34) for sessile serrated polyps, 1.41 (95% CI 1.30-1.52) for tubular adenomas, 2.56 (95% CI 2.36-2.78) for tubulovillous adenomas, and 3.82 (95% CI 3.07-4.76) for villous adenomas (P<0.05 for all subtypes)

• A higher proportion of proximal colon cancers in patients with serrated (hyperplastic and sessile) polyps (52%-57%) than in those with conventional (tubular, tubulovillous, and villous) adenomas (30%-46%)

• A positive association with CRC mortality for sessile serrated polyps (HR 1.74, 95% CI 1.08-2.79), tubulovillous adenomas (HR 1.95, 95% CI 1.69-2.24), and villous adenomas (HR 3.45, 95% CI 2.40-4.95), but not for hyperplastic polyps (HR 0.90, 95% CI 0.76-1.06) or tubular adenomas (HR 0.97, 95% CI 0.84-1.12)

The researchers said they believe their study to be the first to comprehensively characterize CRC incidence and mortality by histological subtypes of polyps in a largely screening-naive population, and no previous study has examined CRC mortality after removal of different subtypes of polyps. "Further studies are needed to examine the impact of colonoscopy surveillance on prevention of colorectal cancer," the team wrote.

Last year, 麻豆传媒 reported that both low- and high-intensity surveillance after polypectomy yielded similar benefits in CRC incidence, with a slight lifetime advantage for the latter approach.

Asked for his perspective, Douglas A. Corley, MD, PhD, of Kaiser Permanente Division of Research in Oakland, California, said the findings were interesting and pose several questions. "In contrast to other recent publications, including large community-based studies with detailed data on polyp size, quality, and bowel preparation, the results suggest that patients who had polyps detected, and presumably completely removed, did not have a lower future risk of colorectal cancer," he told 麻豆传媒.

Other recent studies from the U.S. and elsewhere, however, have indicated that small adenomas and/or hyperplastic polyps confer long-term risks similar to those found with normal colonoscopy. "And the risks for these patients were much lower in the settings where this was evaluated than in unscreened individuals in the same population," Corley continued.

Among the questions raised by the findings, he said, was whether the study patients were at higher CRC risk from family history or other reasons. And could the results be explained largely by an inability to distinguish polyp size so that a small number of high-risk patients with larger polyps were averaged in with low-risk patients? Were there challenges with colonoscopy quality, such as rates of adenoma detection, that tempered the expected protective effect of colonoscopy? Were there challenges with the completeness of the exam or the quality of bowel preparation?

Corley commended the authors for their "detailed evaluation" by polyp type, which he said emphasizes the importance of screening effectiveness in different settings and of understanding the underlying drivers of cancer risk among persons undergoing screening in each setting in order to guide follow-up screening intervals.

A that accompanied the study noted that although polyp removal can substantially reduce CRC mortality, it is not 100% effective at preventing death. "Polyps come in different shapes and sizes and with different microscopic features, and exactly how some characteristics affect patient outcomes is uncertain," wrote Reinier G.S. Meester, PhD, of Erasmus MC University Medical Center in Rotterdam, the Netherlands, and Uri Ladabaum, MD, MS, of Stanford University School of Medicine in California.

Particularly uncertain, they said, is the risk in patients with sessile serrated polyps, a more recently recognized CRC precursor. "Addressing these questions is increasingly urgent as efforts to prevent the disease intensify and more patients have polyps removed," the commentators wrote.

Cautioning that the current study was done in a non-screening setting that might have included persons with more advanced lesions, Meester and Ladabaum said the study's main contribution is the analysis of isolated serrated polyps, including hyperplastic polyps versus sessile serrated polyps, since very few studies have assessed long-term cancer outcomes in these patients, and previous studies were comparatively small.

"Future studies should further clarify the risk after removal of different polyp types, how to best survey patients, and whether further reductions in subsequent risk of cancer incidence and mortality are possible," the commentators wrote.

Study limitations, Ludvigsson and co-authors said, include the use of individuals drawn from the general population as the reference group, which may have underestimated CRC risk in relation to polyps because of the established benefit of endoscopic examination itself and the possibility that some reference individuals might have had undiagnosed polyps because they did not undergo colonoscopy. Because patients with polyps are more likely to receive surveillance endoscopy, there is a risk of detection bias driving the effect estimates of CRC incidence, the researchers noted, which might explain why hyperplastic polyps and tubular adenomas were associated with an increased risk of incidence but not mortality, which is not affected by detection bias.

Moreover, the researchers continued, there was no information on other risk factors such as polyp size and multiplicity, quality, and indication of endoscopy, and lifestyle behaviors such as smoking, obesity, and diet. In addition, endoscopy data were based on procedure coding and subject to measurement error, and therefore the results might not be generalizable to populations in which screening endoscopy is common.

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