Uptake of Colorectal Cancer Screening in 45 to 49 Year Olds: An Early-Inning View from the Endoscopy Suite

Abstract

It has been a year since the US Preventive Services Task Force updated its recommendations for colorectal cancer (CRC) screening,1Davidson K.W. Barry M.J. Mangione C.M. et al.Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement.JAMA. 2021; 325: 1965-1977Crossref PubMed Scopus (260) Google Scholar supporting those initially made by the American Cancer Society2Wolf A.M.D. Fontham E.T.H. Church T.R. et al.Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.CA Cancer J Clin. 2018; 68: 250-281Crossref PubMed Scopus (851) Google Scholar and subsequently by the US Multi-Society Task Force3Patel S.G. May F.P. Anderson J.C. et al.Updates on age to start and stop colorectal cancer screening: recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2022; 162: 285-299Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar to begin average-risk CRC screening at age 45. US Preventive Services Task Force gave this recommendation a “B” rating, which means that there is moderate certainty of net benefit. In 2018, the American Cancer Society conditionally recommended that average-risk screening begin at age 45, whereas the Multi-Society Task Force recommended the starting age of 45 years earlier this year. All 3 organizations based their recommendations on population-based data showing a rising prevalence of CRC in persons younger than age 504Siegel R.L. Miller K.D. Fuchs H.E. et al.Cancer statistics, 2021.CA Cancer J Clin. 2021; 71: 7-33Crossref PubMed Scopus (7572) Google Scholar and the results of 3 independent simulation models demonstrating a reasonable balance of benefit and risk.5Peterse E.F.P. Meester R.G.S. Siegel R.L. et al.The impact of the rising colorectal cancer incidence in young adults on the optimal age to start screening: microsimulation analysis I to inform the American Cancer Society colorectal cancer screening guideline.Cancer. 2018; 124: 2964-2973Crossref PubMed Scopus (127) Google Scholar, 6Meester R.G.S. Peterse E.F.P. Knudsen A.B. et al.Optimizing colorectal cancer screening by race and sex: microsimulation analysis II to inform the American Cancer Society colorectal cancer screening guideline.Cancer. 2018; 124: 2974-2985Crossref PubMed Scopus (52) Google Scholar, 7Knudsen A.B. Zauber A.G. Rutter C.M. et al.Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force.JAMA. 2016; 315: 2595-2609Crossref PubMed Scopus (312) Google Scholar Lowering the age at which to begin average-risk screening by 5 years adds approximately 20 million people who now require screening.8Crockett S.D. Ladabaum U. Potential effects of lowering colorectal cancer screening age to 45 years on colonoscopy demand, case mix, and adenoma detection rate.Gastroenterology. 2022; 162: 984-986Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Although CRC screening in 45–49 year olds does not automatically equate with “screening colonoscopy,” colonoscopy is the most commonly used screening test, with more than 11 million performed annually in the United States.9Peery A.F. Crockett S.D. Murphy C.C. et al.Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018.Gastroenterology. 2019; 156: 254-272Abstract Full Text Full Text PDF PubMed Scopus (644) Google Scholar Accommodating 45–49 year olds raises questions deserving of consideration. Who among 45–49 year olds will get screened? Will those who submit to screening represent “average-risk” 45–49 year olds or will they comprise a high-risk subgroup (perhaps with low-grade, unreported symptoms, a family history, or both) or low-risk subgroup (healthy and health conscious)? How will they choose to be screened (with colonoscopy or noninvasively)? How will screening 45–49 year olds affect access to screening colonoscopy for older persons and for other indications, such as neoplasia surveillance? If uptake in 45–49 year olds is brisk, how can (and will) colonoscopy capacity increase? From a quality perspective, what effect will 45–49 year olds have on adenoma detection rates (ADR), the most evidence-based measure of colonoscopy quality?10Corley D.A. Jensen C.D. Marks A.R. et al.Adenoma detection rate and risk of colorectal cancer and death.N Engl J Med. 2014; 370: 1298-1306Crossref PubMed Scopus (1128) Google Scholar,11Kaminski M.F. Regula J. Kraszewska E. et al.Quality indicators for colonoscopy and the risk of interval cancer.N Engl J Med. 2010; 362: 1795-1803Crossref PubMed Scopus (1363) Google Scholar Should the benchmarks for ADR be lowered because of anticipated lower adenoma prevalence in 45–49 year olds? Although it is too early for clear and definitive answers to these questions, the study by Ladabaum et al12Ladabaum U. Shepard J. Mannalithara A. Adenoma and sessile serrated lesion detection rates at screening colonoscopy for ages 45-49 years vs older ages since the introduction of new colorectal cancer screening guidelines.Clin Gastroenterol Hepatol. 2022; 20: 2895-2904Abstract Full Text Full Text PDF Scopus (1) Google Scholar provides robust first-look answers to some of them. The study is based on colonoscopic and histologic data from the Stanford Colonoscopy Quality Assurance Program, which was established in the Fall of 2017 and contains information on all colonoscopies performed in 4 geographically separate endoscopy units affiliated with endoscopists from Stanford University and Stanford Health Care System.13Ladabaum U. Stanford Colonoscopy Quality Assurance Program: lessons from the intersection of quality improvement and clinical research.Gastroenterology. 2021 Oct 12; (S0016-5085(21)03621-0)Abstract Full Text Full Text PDF Google Scholar,14Ladabaum U. Mannalithara A. Desai M. et al.Age-specific rates and time-courses of gastrointestinal and nongastrointestinal complications associated with screening/surveillance colonoscopy.Am J Gastroenterol. 2021; 116: 2430-2445Crossref PubMed Scopus (3) Google Scholar The investigators examined nearly 8000 first-time or rescreening colonoscopies with documented cecal intubation and Boston Bowel Preparation Scores of ≥2 in each colonic segment, dividing the colonoscopies into 2 periods: Period I (October 2017 through December 2018) representing the time before the 2018 updated ACS guideline, and Period II (January 2019 through August 2021) representing the postguideline period. Prevalence of any adenoma, advanced adenoma, any sessile serrated lesion, advanced sessile serrated lesion, adenomas per colonoscopy, and lesions per colonoscopy were analyzed according to first screening or rescreening, with patients divided into 5-year age groups from <45 years to ≥85 years. Both overall and age group–specific prevalence rates were calculated and compared between Periods I and II. Patients 45–49 years old were compared specifically with initial screening of 50–54 year olds and with rescreening of 50–75 year olds, the aim of this latter comparison to determine the rescreening age subgroup with lesion prevalence most comparable with 45–49 year olds’ index screening results. The main study findings are: (1) the proportion of first-time screening colonoscopies in 45–49 year olds increased by just over 8%, from 3.5% in Period I to 11.6% in Period II, while decreasing modestly (a net decline of 8.7%) across all other age categories; (2) Period II detection rates for all lesions were only slightly higher for 50–54 year olds than for 45–49 year olds; (3) for nearly all lesions and in nearly all age groups, detection rates were higher in Period II; and (4) lesion prevalence for index screening colonoscopy findings in 45–49 year olds was most closely matched to rescreening colonoscopic findings in 60–64 year olds. The authors are to be complimented for their well-organized and thoughtful reporting of this first observation of screening colonoscopy uptake of 45–49 year olds. They have established a reporting framework for other investigators. Because of feasibility issues, data on CRCs detected were not available, a minor limitation given the likely imprecise point estimates for any age category and for both reporting periods. Prevalence of any adenoma and advanced adenoma are broadly comparable with previous reports of screening colonoscopy in persons younger than 50 years,9Peery A.F. Crockett S.D. Murphy C.C. et al.Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018.Gastroenterology. 2019; 156: 254-272Abstract Full Text Full Text PDF PubMed Scopus (644) Google Scholar,15Kolb J.M. Hu J. DeSanto K. et al.Early-age onset colorectal neoplasia in average-risk individuals undergoing screening colonoscopy: a systematic review and meta-analysis.Gastroenterology. 2021; 161: 1145-1155Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,16Liang P.S. Williams J.L. Dominitz J.A. et al.Age-stratified prevalence and predictors of neoplasia among US adults undergoing screening colonoscopy in a national endoscopy registry.Gastroenterology. 2022 May 26; (S0016-5085(22)00527-3.)Abstract Full Text Full Text PDF Scopus (1) Google Scholar with the limitation that these previous reports of screening colonoscopy in persons younger than 50 may have included a higher-than-average proportion of persons with 1 or more first-degree relatives with CRC. There is little reason to question the validity of the findings by Ladabaum et al,12Ladabaum U. Shepard J. Mannalithara A. Adenoma and sessile serrated lesion detection rates at screening colonoscopy for ages 45-49 years vs older ages since the introduction of new colorectal cancer screening guidelines.Clin Gastroenterol Hepatol. 2022; 20: 2895-2904Abstract Full Text Full Text PDF Scopus (1) Google Scholar given their comparability with previous studies and their face validity (ie, the findings make sense). We have begun seeing 45–49 year olds for screening colonoscopy or for diagnostic colonoscopy following a positive noninvasive screening test, and separately see ADRs increasing through quality improvement initiatives and advances in technology. What remains uncertain is their generalizability: how well do they reflect what is happening in other areas of the country and in other health care systems, some of which may lead with noninvasive screening? Given this perspective, what does the study by Ladabaum et al12Ladabaum U. Shepard J. Mannalithara A. Adenoma and sessile serrated lesion detection rates at screening colonoscopy for ages 45-49 years vs older ages since the introduction of new colorectal cancer screening guidelines.Clin Gastroenterol Hepatol. 2022; 20: 2895-2904Abstract Full Text Full Text PDF Scopus (1) Google Scholar help us understand about the early diffusion of CRC screening among 45–49 year olds? What remains to be determined? Perhaps most significantly, we see that detection rates between 45–49 year olds and 50–54 year olds were nearly the same, with differences even smaller than the findings of Bilal et al,17Bilal M. Holub J. Greenwald D. et al.Adenoma detection rates in 45-49-year-old persons undergoing screening colonoscopy: analysis from the GIQuIC Registry.Am J Gastroenterol. 2022; 117: 806-808Crossref PubMed Scopus (3) Google Scholar who compared adenoma prevalence between these 2 age groups using 2014–2020 screening colonoscopy data from the GIQuIC registry. Given population-based data on CRC incidence, this more current close similarity between the 2 age groups should not be surprising. The modest uptake of screening colonoscopy in 45–49 year olds, with its minimal effect on age distribution, suggests that there is no need to reduce ADR benchmarks at this point. Rather, the improvement in lesion detection from Period I to Period II, whether caused by increases in age-specific prevalence, the success of quality improvement initiatives, technology, or any combination, provides support for increasing them. As a sidenote, it remains unclear as to whether the ADR will remain the only validated measure of colonoscopy quality, because evidence for other quality metrics, such as adenomas per colonoscopy,18Wang S. Kim A.S. Church T.R. et al.Adenomas per colonoscopy and adenoma per positive participant as quality indicators for screening colonoscopy.Endosc Int Open. 2020; 8 (E1560-e5)Google Scholar,19Gessl I. Waldmann E. Penz D. et al.Evaluation of adenomas per colonoscopy and adenomas per positive participant as new quality parameters in screening colonoscopy.Gastrointest Endosc. 2019; 89: 496-502Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar and other measures is emerging.20Anderson J.C. Hisey W. Mackenzie T.A. et al.Clinically significant serrated polyp detection rates and risk for postcolonoscopy colorectal cancer: data from the New Hampshire Colonoscopy Registry.Gastrointest Endosc. 2022; 96: 310-317Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar,21Wieszczy P. Bugajski M. Januszewicz W. et al.Comparison of quality measures for detection of neoplasia at screening colonoscopy.Clin Gastroenterol Hepatol. 2022 Mar 24; (S1542-3565(22)00298-1)Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Down the road, the adenomas per colonoscopy and other metrics could well supplant ADR, or more likely, colonoscopy quality may best be measured by a combination of 1 or more detection metrics along with a measure of polypectomy quality. What do we not yet know? We cannot know what segment of 45–49 year olds has thus far shown up for screening, with colonoscopy or otherwise. Do they represent average-, low-, or high-risk individuals in this age group? Only with continued monitoring of the yield of neoplastic lesions over time will this become clearer. We also cannot yet know whether the modest Period II reduction in initial screening colonoscopy for persons ≥50 years will continue and if it does, at what rate it will progress, and with what consequences. If a large segment of 45–49 year olds chooses screening colonoscopy, it could decrease access for older persons, for whom colonoscopy for screening, diagnosis, and surveillance of persons with high-risk neoplasms is arguably more important. This possible scenario is a reminder of our need to be good stewards of colonoscopy. Strategies to mitigate this possibility include greater use of noninvasive screening for 45–49 year olds, either with fecal immunochemical testing or fecal immunochemical testing/DNA, both of which have very good or excellent specificity in this age group.22Imperiale T.F. Gruber R.N. Stump T.E. et al.Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: a systematic review and meta-analysis.Ann Intern Med. 2019; 170: 319-329Crossref PubMed Scopus (86) Google Scholar,23Imperiale T.F. Kisiel J.B. Itzkowitz S.H. et al.Specificity of the multi-target stool DNA test for colorectal cancer screening in average-risk 45-49 year-olds: a cross-sectional study.Cancer Prev Res (Phila). 2021; 14: 489-496Crossref PubMed Scopus (13) Google Scholar An effective strategy for consideration is to start screening at age 45 noninvasively, and use the “hybrid” strategy of noninvasive screening before age 50 followed by colonoscopic screening, part of an excellent and thoughtful cost-effectiveness analysis done by the same authors,24Ladabaum U. Mannalithara A. Meester R.G.S. et al.Cost-effectiveness and national effects of initiating colorectal cancer screening for average-risk persons at age 45 years instead of 50 years.Gastroenterology. 2019; 157: 137-148Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar who also clearly show that a fixed amount of screening resources is more effectively and efficiently directed to screening of older persons. Effective use of noninvasive screening will require design of robust tracking systems, ensuring diagnostic colonoscopy for positive noninvasive tests and repeat testing at the appropriate interval for negative ones. Some degree of risk stratification for the risk of advanced neoplasia may be useful in 45–49 year olds for directing initial use of screening colonoscopy to those at high risk. Lastly, we can consider ways to improve colonoscopy efficiency among older persons by elongating rescreening intervals based on procedure-related factors (eg, prep quality, endoscopist ADR). In the current study, the prevalence of index colonoscopic findings in 45–49 year olds was most comparable to rescreening findings in 60–64 year olds, for whom prevalence of advanced adenomas and advanced sessile serrated lesions was 6.3% and 2.9% versus 6.1% and 2.3%, respectively. Although the size and histology of advanced adenomas were not compared, this finding provides some support for longer rescreening intervals, which would create colonoscopy capacity. Rescreening colonoscopy for some persons in their early 60s may be too early (assuming that the previous one was in their early 50s), because studies of high-quality colonoscopy suggest up to 17 years of protection against CRC,25Pilonis N.D. Bugajski M. Wieszczy P. et al.Long-term colorectal cancer incidence and mortality after a single negative screening colonoscopy.Ann Intern Med. 2020; 173: 81-91Crossref PubMed Scopus (43) Google Scholar and that the value of surveillance for low-risk neoplasia is uncertain.26Duvvuri A. Chandrasekar V.T. Srinivasan S. et al.Risk of colorectal cancer and cancer related mortality after detection of low-risk or high-risk adenomas, compared with no adenoma, at index colonoscopy: a systematic review and meta-analysis.Gastroenterology. 2021; 160: 1986-1996Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Like many well-done studies, the study by Ladabaum et al12Ladabaum U. Shepard J. Mannalithara A. Adenoma and sessile serrated lesion detection rates at screening colonoscopy for ages 45-49 years vs older ages since the introduction of new colorectal cancer screening guidelines.Clin Gastroenterol Hepatol. 2022; 20: 2895-2904Abstract Full Text Full Text PDF Scopus (1) Google Scholar provides clear and valid answers to some questions but raises others, the answers to which are pending. Perhaps the most significant contribution of their work is the reporting framework and clarity of presentation. We expect other investigators to report on current and subsequent diffusion of CRC screening in 45–49 year olds. It is likely that the diffusion will vary based on region of the country, health care system, access to care, patient preferences, and other factors. We await analyses like those of Ladabaum et al12Ladabaum U. Shepard J. Mannalithara A. Adenoma and sessile serrated lesion detection rates at screening colonoscopy for ages 45-49 years vs older ages since the introduction of new colorectal cancer screening guidelines.Clin Gastroenterol Hepatol. 2022; 20: 2895-2904Abstract Full Text Full Text PDF Scopus (1) Google Scholar from others, with the distinct possibility that a more complete understanding of uptake, yield, and other outcomes may require quantitative systematic reviews of these studies. Ladabaum et al12Ladabaum U. Shepard J. Mannalithara A. Adenoma and sessile serrated lesion detection rates at screening colonoscopy for ages 45-49 years vs older ages since the introduction of new colorectal cancer screening guidelines.Clin Gastroenterol Hepatol. 2022; 20: 2895-2904Abstract Full Text Full Text PDF Scopus (1) Google Scholar have blazed the reporting pathway for these subsequent investigations. Adenoma and Sessile Serrated Lesion Detection Rates at Screening Colonoscopy for Ages 45–49 Years vs Older Ages Since the Introduction of New Colorectal Cancer Screening GuidelinesClinical Gastroenterology and HepatologyVol. 20Issue 12PreviewAll major U.S. guidelines now endorse average-risk colorectal cancer (CRC) screening at 45–49 years of age. Concerns exist that endoscopic capacity may be strained, that low-risk persons may self-select for screening, and that calculations of the adenoma detection rate may be diluted. We analyzed age-specific screening colonoscopy volumes and lesion detection rates before vs after the endorsement of CRC screening at 45–49 years of age. Full-Text PDF