Long-term Risk of Colorectal Cancer After Removal of Conventional Adenomas and Serrated Polyps

doi:10.1053/j.gastro.2019.06.039

Gastroenterology

Volume 158, Issue 4, March 2020, Pages 852-861.e4

https://doi.org/10.1053/j.gastro.2019.06.039 Get rights and content

Background & Aims

Endoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance.

Methods

We examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses’ Health Study 1 (1990–2012), Nurses’ Health Study 2 (1989–2013), or the Health Professionals Follow-up Study (1990–2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (≥10 mm, high-grade dysplasia, or tubulovillous or villous histology) or nonadvanced, and serrated polyps were assigned to categories of large (≥10 mm) or small (<10 mm). We used a Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors.

Results

After a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared with participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% confidence interval [CI] 2.89–5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI 1.37–8.15). In contrast, there was no significant increase in risk of CRC in patients with nonadvanced adenomas (HR 1.21; 95% CI 0.68–2.16, P = .52) or small serrated polyps (HR 1.25; 95% CI 0.76–2.08; P = .38).

Conclusions

These findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with nonadvanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps.

Graphical abstract

Section snippets

Study Population

The NHS included 121,700 US female nurses aged 30 to 55 at enrollment in 1976. The NHS2 included 116,430 registered US female nurses aged 25 to 42 years at the time of enrollment in 1989. The HPFS enrolled 51,529 male health professionals aged 40 to 75 at enrollment in 1986. Participants were mailed a questionnaire at baseline and every 2 years thereafter that inquired about detailed medical and lifestyle information, including history of endoscopic examinations and diagnosis of colorectal

Results

Based on the findings of the first lower endoscopies among 122,899 participants, we identified 6161 cases with at least 1 conventional adenoma, 5918 with SP (1287 [22%] of those also had conventional adenomas), and 112,107 with no polyp. As shown in Table 1, compared with participants with no polyp at the first endoscopy, those with polyps were more likely to have a family history of CRC, smoke, drink alcohol, and have a higher body mass index; and were less likely to exercise and regularly use

Discussion

Within 3 large prospective US cohorts with a median follow-up of 10 years since the first endoscopy, we observed that individuals with advanced adenoma or large SP were more likely to develop CRC compared with participants with no polyp. Through detailed analysis according to adenoma features, we found that large size, multiplicity, and villous histology all predicted a higher CRC risk. In contrast, individuals with nonadvanced adenoma or small SP did not have an increased risk of CRC. Our

Acknowledgments

We thank the participants and staff of the Nurses’ Health Study, the Nurses’ Health Study 2, and the Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.

Author contributions: A.T.C. and

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High-risk adenomas predict metachronous advanced adenomatous neoplasia. Limited data exist on predictors of metachronous advanced serrated lesions (mASLs). We analyzed clinical and endoscopic predictors of mASLs.
In this retrospective cohort study, adults with >1 outpatient colonoscopy between 2008 and 2019 at a tertiary center were included. Serrated lesions (SLs) included sessile SLs (SSLs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). Patient and endoscopic characteristics were obtained using electronic medical records. Five-year cumulative incidence of mASL (HP ≥10 mm, SSL ≥10 mm or with dysplasia, any TSA) and factors associated with mASL were evaluated using Kaplan-Meier estimates and Cox proportional hazards models.
A total of 4990 patients were included and 45.4% were women. Mean age was 60.9 ± 9.2 years and median follow-up time was 3.7 years. Female sex and active smoking were associated with mASL. Endoscopically, any SSL and TSA were associated with mASL. The 5-year cumulative incidence for mASL was 26% (95% confidence interval [CI], 18%–32%) for SSL ≥10 mm, 17% (95% CI, 3.5%–29%) for HP ≥10 mm, 21% (95% CI, 0%–42%) for 3–4 SSLs <10 mm, 18% (95% CI, 0%–38%) for TSA, and 27% (95% CI, 3.6%–45%) for SSL with low-grade dysplasia. Baseline synchronous nonadvanced SL and nonadvanced adenoma were not associated with mASL.
Our data support current recommendations for a 3-year surveillance interval in patients with baseline SSL ≥10 mm, SSL with dysplasia, and TSA. A 3-year interval may be more appropriate than 3–5 years for patients with baseline HP ≥10 mm or 3–4 SSLs <10 mm. Patients with synchronous nonadvanced SLs and adenomas do not appear to be at increased risk of mASL.
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We retrieved data from a cohort of patients undergoing postpolypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were postpolypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia, and location of the index lesion. We adopted as comparators FIT+/colonoscopy-negative and FIT– patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables.
Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had an LRA, and 22,709 (26.0%) an HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.92–1.53) was not increased compared with the FIT+/colonoscopy-negative group, while for HRAs a significant increase in CRC incidence (HR, 1.53; 95% CI, 1.14–2.04) was found. The presence of 1 or more risk factors among proximal location, nonpedunculated morphology, and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR, 1.85; 95% CI, 1.36–2.52). Patients with only distal pedunculated polyps without high-grade dysplasia, representing 39.2% of HRA, did not have increased risk compared with the FIT– group (HR, 0.87; 95% CI, 0.59–1.28).
CRC incidence is significantly higher in patients with HRAs diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without high-grade dysplasia, an observation that could potentially reduce the burden of surveillance in FIT programs.
Differences in circulating lymphocyte subpopulations among patients with inflammatory polyps, colorectal adenomas and colorectal cancer
2024, Arab Journal of Gastroenterology
Colorectal cancer (CRC) may develop from focal changes within benign or precancerous polyps. The immune system’s failure to detect and eradicate tumor cells due to immune surveillance evasion, allows cancer to develop and spread. This study aims to analyze the differences in circulating lymphocyte subpopulations in patients with colorectal inflammatory polyps, colorectal adenomas and CRC.
We retrospectively reviewed patients from September 2016 to December 2019 at the Shaoxing Second Hospital. Using flow cytometry, the subset distribution and immunophenotype of T cells, CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells were investigated in peripheral blood mononuclear cell samples. The counts of lymphocytes were determined by white blood cell counts.
In total, 518 patients were included in this study. The counts of lymphocytes, T cells and NK cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts and percentages of CD8⁺ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts of CD4⁺ T cells were lower in patients with CRC than inflammatory polyps. The percentages of CD4⁺ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were higher than controls, but lower in the CRC than inflammatory polyps, colorectal adenomas. The counts and percentages of B cells were lower in CRC patients than colorectal adenomas patients. In addition, the percentages of B cells were higher in patients with inflammatory polyps and colorectal adenomas than in controls.
The decrease in counts of lymphocyte, T cells, CD8⁺ T cells and NK cells in patients may be related to the dysplasia of epithelial cells. Furthermore, the B cells and CD4⁺ T cells may be related to the malignant growth of the dysplastic epithelial cells.
Randomized Trial of Patient Outreach Approaches to De-implement Outdated Colonoscopy Surveillance Intervals
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Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7–10 years and those with the previously recommended 5-year interval be re-evaluated. We tested 3 outreach approaches for transitioning patients to the 10-year interval recommendation.
This was a 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. The setting was Kaiser Permanente Northern California, a large integrated healthcare system. Participants were patients 54–70 years of age with 1–2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all 3 outreach modalities. Patients were randomly assigned to the outreach arm (telephone [n = 200], secure message [n = 203], and mailed letter [n = 201]) stratified by age, sex, and race/ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2–4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval.
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: Conflicts of interest Andrew T. Chan previously served as a consultant for Bayer Healthcare and Pfizer Inc. for work unrelated to the topic of this manuscript. This study was not funded by Bayer Healthcare or Pfizer Inc. The other authors disclose no conflicts.

: Funding This work was supported by the American Cancer Society Mentored Research Scholar Grant (MRSG-17-220-01-NEC to M.S.); by the US National Institutes of Health grants [P01 CA87969 to M.J. Stampfer; UM1 CA186107 to M.J. Stampfer; P01 CA55075, to W.C. Willett; UM1 CA167552 to W.C. Willett; P50 CA127003 to C.S. Fuchs; K24 DK098311, R01 CA137178, R01 CA202704, R01 CA176726, to A.T.C.; R01 CA151993, R35 CA197735 to S.O.; CA202704, R01 CA176726, to A.T.C.; R01 CA151993, R35 CA197735 to S.O.; R03 CA197879 to K.W.; R21 CA230873 to K.W. and S.O.; R21 CA230873 to K.W. and S.O.; K99 CA215314 and R00 CA215314 to M.S.]; by National Key R&D Program of China [2017YFC1308800 to X.H.; 2017YFC0908300 to D.H.] and by grants from the American Institute for Cancer Research (K.W.), the Project P Fund for Colorectal Cancer Research, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. Andrew T. Chan is a Stuart and Suzanne Steele MGH Research Scholar. The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

: Author names in bold designate shared co-first authorship.

^∗: Authors share co-first authorship

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Original ResearchFull Report: Clinical—Alimentary TractLong-term Risk of Colorectal Cancer After Removal of Conventional Adenomas and Serrated Polyps

Background & Aims

Methods

Results

Conclusions

Graphical abstract

Section snippets

Study Population

Results

Discussion

Acknowledgments

Lancet

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

CA Cancer J Clin

Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths

N Engl J Med

Long-term colorectal-cancer incidence and mortality after lower endoscopy

N Engl J Med

Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial

JAMA

Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)

Gut

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Colonoscopic surveillance following adenoma removal

Endoscopy

Original Research
Full Report: Clinical—Alimentary Tract
Long-term Risk of Colorectal Cancer After Removal of Conventional Adenomas and Serrated Polyps