Posted on May 19, 2022

In Case You Missed It
Wait 7-10 Years for Repeat Colonoscopy If You Only Find 1-2 Small Adenomas… It’s Not Too Long!

Swati G. Patel, MD, MS

Associate Professor of Medicine, University of Colorado School of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado

This summary reviews Click B, Pinsky PF, Hickey T, Doroudi M, Schoen, RE. Association of Colonoscopy Adenoma Findings with Long-Term Colorectal Cancer Incidence. JAMA 2018; 319(19): 2022-2031.

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Correspondence to Swati G. Patel, MD, MS, Associate Editor. Email: EBGI@gi.org

STRUCTURED ABSTRACT

Question: Is the long-term risk of colorectal cancer (CRC) different between individuals with 1-2 non-advanced (<10mm) adenomas vs no adenomas?

Study Design: Multi-center, prospective cohort from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Study. This study only examines PLCO patients randomized to receive flexible sigmoidoscopy and had a polyp or mass found and subsequently completed a colonoscopy.

Setting: Participants were recruited from 1993-2001 from 10 centers participating in PLCO.

Patients: Average-risk 55-74-year-olds who had a polyp or mass in the distal colon on flexible sigmoidoscopy, and then completed a follow up colonoscopy were included.  Participants diagnosed with cancer at time of colonoscopy and those with no follow up time were excluded. Of the 15,935 participants included, 2,882 participants (18.1%)  had an advanced adenoma, 5,068 participants (31.8%) had non-advanced adenomas, and 7,985 participants (50.1%) had no adenoma (i.e., hyperplastic polyp or no polyp found at colonoscopy). The median age was 64 (IQR: 61-68), 59.7% were men, 90.7% were White, and median follow up was 12.9 years (IQR: 9.8-15).

Exposure: Index colonoscopy with no adenoma, 1-2 non-advanced adenomas (< 10 mm) or advanced adenoma (adenoma ≥ 10 mm, with highgrade dysplasia or villous architecture).

Outcomes: Primary outcome was CRC incidence within 15 years of baseline colonoscopy. Secondary outcome was CRC mortality.
Results: Over a median 12.9 years of follow up, CRC incidence per 10,000-person years was 20.0, 9.1, and 7.5 in those with advanced adenomas, non-advanced adenomas, and no adenomas, respectively. Cumulative incidence of CRC over 15 years was 2.9%, 1.4%, and 1.2%, respectively, in those groups. Although those with advanced adenomas were significantly more likely to develop CRC (relative risk = 2.7; 95% CI: 6.7-11.5) compared to those with no adenoma, there was no significantly increased risk of CRC in
those with non-advanced adenomas compared to those with no adenomas (RR = 1.2; 95% CI: 0.8-1.7) (Figure 1). The cumulative CRC incidence was similar between individuals with non-advanced adenomas and no adenomas at 5 years, 7 years, and 10 years from index colonoscopy (illustrated in Figure 2 of Click et al). The risk of CRC mortality was significantly increased in those with advanced adenomas (RR 2.6, 95% CI 1.2-5.7) compared to those with no adenomas. Again, those with nonadvanced adenomas were not at increased risk of mortality compared to those with no adenomas (Figure 1).
Funding: National Cancer Institute.

COMMENTARY

Why Is This Important?
This research, along with 2 meta-analyses and European cohort studies, provide the foundation for the United States Multi-Society Task Force on Colorectal Cancer recommendation in 2020 to extend surveillance intervals to 7-10 years for average-risk individuals with 1-2 small or non-advanced adenomas on index screening colonoscopy.1 The PLCO study was crucial because its large size (n = 15,935), prolonged follow-up (median 12.9 years), and comprehensive follow-up (93.8% compliance with annual study  update on health) provided precise estimates of CRC incidence in the no adenoma and 1-2 small adenoma group.

Key Study Findings
Patients diagnosed with 1-2 non-advanced adenomas have the same long-term risk of colorectal cancer and death from colorectal cancer as those with no adenomas (Figure 1). Those with advanced adenomas have a 2.7-fold increased risk of developing CRC and a 2.6-fold increased risk of dying from CRC.

Figure 1. Realtive risk of CRC and CRC mortality based on adenoma findings.

Caution
There was insufficient data to draw a conclusion about whether patients with three or more adenomas have an increased risk of CRC. This study was also conducted in an era  before there was a strong commitment to colonoscopy quality (before split-dose bowel preparations, high-definition colonoscopes, adenoma detection monitoring, serrated lesion detection monitoring, endoscopic mucosal resection techniques). Most importantly, use of surveillance colonoscopy was only tracked for 21.9% of the study population,
and surveillance colonoscopy was used more frequently in patients with 1-2 small adenomas (78.1%) vs individuals with no adenomas (69.9%). So, differences in use of  surveillance colonoscopy could partly account for similarity of CRC incidence in these groups.

My Practice
This high-quality study, along with other recent meta-analyses and European cohort studies cited in the 2020 USMSTF on CRC Screening Guideline, I strongly support extending surveillance intervals for those with 1-2 small tubular adenomas. If a patient has undergone a high-quality colonoscopy (adequate bowel preparation, complete to cecum, high-adenoma detection rate provider, complete polyp resection), I recommend 7-year surveillance for those with 1-2 small adenomas and additional risk factors (male sex, smokers, metabolic syndrome/diabetes, obesity, > age 60) and 10-year surveillance for those without additional risk factors and under age 60.

For Future Research
Validation that 1-2 small adenomas truly confer low risk of future CRC through a prospective randomized controlled trial of different surveillance intervals is currently  underway (the FORTE trial, NCT05080673). We also still need studies to assess long-term CRC risk in patients with three or more small tubular adenomas and studies in the contemporary era of high-quality colonoscopy to validate whether intensive surveillance of advanced adenomas is still warranted.

REFERENCE
1. Gupta S, Lieberman D, Anderson JC, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020;158:1131-1153 e5.

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