Colorectal cancer screening for average risk adults: 2018 guideline update from the American Cancer Society

Andrew M. D. Wolf MD Elizabeth T. H. Fontham MPH, DrPH Timothy R. Church PhD Christopher R. Flowers MD, MS Carmen E. Guerra MD Samuel J. LaMonte MD … See all authors


In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a highsensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) averagerisk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;000:000-000. © 2018 American Cancer Society.


Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer among adults in the United States.1 Over 140,000 Americans are expected to be diagnosed with CRC in 2018. It is the second leading cause of cancer death, leading to over 50,000 deaths annually.1 CRC disease burden varies across racial groups, with the highest incidence and mortality rates in blacks, American Indians, and Alaska Natives.2 Temporal trends in CRC incidence and mortality among adults aged 55 years and older have shown a decline for several decades that accelerated around 2000, particularly among adults aged 65 years and older.2, 3 Although changes in exposure to risk factors account for an estimated one-half of the reduction in incidence and one-third of the reduction in mortality before 2000, subsequent accelerated declines in incidence and mortality since 2000 are largely attributable to increased uptake of screening, with improved treatment also contributing to mortality reductions.3-6 In contrast, among adults younger than 55 years, there was a 51% increase in the incidence of CRC from 1994 to 2014 and an 11% increase in mortality from 2005 to 2015.7, 8 Risk factors associated with a Western lifestyle that have been shown to increase CRC risk include: cigarette smoking; excess body weight; diet, including high consumption of alcohol and red and processed meat and low consumption of fruits/vegetables, dietary fiber, and dietary calcium; and physical inactivity.9, 10 Islami et al estimated that a significant proportion of CRC incidence among women and men in 2014 (50.8% and 58.2%, respectively) was attributable to these lifestyle factors.10 Thus, there is an important opportunity to reduce risk across the population through lifestyle modification. The use of aspirin in selected individuals has also been demonstrated to reduce the likelihood of developing CRC.11-14 Risk for developing CRC is associated with several identified hereditary CRC conditions; a family history of CRC15; medical conditions, including chronic inflammatory bowel disease16 and type 2 diabetes17; and a history of abdominal or pelvic radiation for a previous cancer.18-21 The detection and subsequent removal of precursor lesions detected during screening and the detection of CRC at an earlier, more favorable stage have been shown to significantly reduce incidence and mortality. The increased understanding of the natural history of CRC and precursor lesions and the development and accumulation of evidence on screening technologies have supported the evolution of screening recommendations and implementation of CRC screening in clinical practice and public health programs.22 This guideline is intended to provide guidance to adults at average risk of CRC, to clinicians who counsel and refer patients to CRC screening, and to health care systems to support best practices in the early detection and prevention of CRC. The American Cancer Society (ACS) first published evidence-based recommendations for early detection of cancer of the colon and rectum in 1980.23 The most recent update of recommendations for individuals at average risk occurred in 2008 and was based on an evidence-based consensus process that included the ACS, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (representing the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy), and the American College of Radiology.24 Since 2008, evidence has accumulated on the different screening modalities, test performance in population-based screening programs, and the changing risk of CRC.3, 25, 26 This guideline update is based on an assessment of the underlying burden of disease; the strength of evidence and the balance of benefits and harms for available screening tests; and consideration of patient values and preferences, including the importance of choice in the selection of screening test options.

Materials and Methods

The ACS follows a protocol for developing and disseminating guidelines that is designed to maintain transparency, consistency, and rigor.27, 28 This process includes the use of systematic evidence reviews on the topic, consideration of the overall balance of benefits and harms of interventions and patient preferences, a guidelines panel of scientific experts without any direct professional specialization in the issue under review, a transparent disclosure and management process that minimize biases and conflicts of interest, explicit explanation of the logical relationships between screening interventions and health outcomes, and ratings of both the quality of evidence and the strength of the recommendations. The ACS Guideline Development Group (GDG), a multidisciplinary panel of volunteers comprising generalist clinicians, biostatisticians, epidemiologists, economists, and a patient representative, is charged with the development and update of the ACS cancer screening guidelines. The GDG has full responsibility for interpretation of the evidence, formulating the recommendations, deliberation and voting on the recommendations and strength, and writing the guideline. A record of voting on the recommendations is kept without attribution. While the GDG attempts to achieve complete agreement, a three-quarters majority is considered acceptable for adopting a recommendation and assigning strength. For the update of the CRC screening guideline, a subcommittee consisting of 6 GDG members had primary responsibility for reviewing the evidence, drafting recommendations, and preparing the manuscript for publication, although the entire GDG reviewed and voted on the updated guideline. ACS staff members served as guideline methodologists and in an administrative capacity to support the GDG. ACS staff members also contributed cancer screening and CRC expertise to the GDG evaluation of the evidence and participated in preparation of the manuscript but did not formulate recommendations or vote to approve the final guideline. Guideline development is supported by ACS general operating funds. Individuals with recognized clinical and research expertise in the areas of CRC natural history, detection, diagnosis, and decision making were invited to advise the GDG and to provide broader knowledge and understanding of the complexity of CRC screening (see Supporting Information). The GDG consulted the expert advisors at several stages in the guideline development process: the expert advisors were requested to respond to questions about the key evidence questions and the evidence and logic underlying screening recommendations and to assess the primary evidence reports and suggest additional data for consideration. In addition, they served as external reviewers of the draft recommendation statements and the guideline manuscript before publication. Participants (GDG members, ACS staff, expert advisors) in all stages of the guideline development process were required to disclose all financial and nonfinancial (personal, intellectual, practice-related) relationships and activities that might be perceived as posing a conflict of interest in the update of the CRC screening guideline. The GDG chairpersons had the responsibility to ensure balanced perspectives were considered in deliberations and decision making. For the update of the CRC screening guideline, the GDG chose to use 2 reports commissioned by the US Preventive Services Task Force (USPSTF) for its 2016 CRC screening recommendation update as sources of evidence to inform recommendations: a systematic evidence review on CRC screening and a report of simulation modeling findings from the Cancer Intervention and Surveillance Modeling Network (CISNET) CRC group.26, 29-31 The evidence synthesis conducted for the USPSTF addressed 3 issues: the effectiveness of screening in reducing incidence and mortality from CRC, the test performance characteristics of different screening tests for detecting CRC and important precursor lesions, and the adverse effects associated with different screening tests. Three microsimulation models of CRC screening developed as part of the CISNET consortium estimated the impact of a variety of programmatic screening strategies for the screening-eligible US population. The CISNET-CRC group consists of 3 CRC microsimulation models that were independently developed for the evaluation of interventions, and their use to date principally has focused on screening. The 3 models differ somewhat in their underlying assumptions about the natural history of CRC, which allows for estimation of outcomes based on these different assumptions. The CISNET-CRC models include: 1) MISCAN-CRC, with investigators from Erasmus University Medical Center and Memorial Sloan Kettering Cancer Center; 2) SimCRC from the University of Minnesota and Massachusetts General Hospital; and 3) CRC-SPIN from RAND Corporation.32 To gain additional understanding of outcomes associated with different screening strategies (particularly starting age) for black and white adults, the ACS commissioned a modeling study by the MISCAN and SimCRC investigators (2 of the CISNET modeling groups) that extended the previous analysis conducted for the USPSTF. The objective was to assess the potential benefit (lifeyears gained and CRC deaths averted) and the burden of different CRC screening strategies for black and white women and men.33 Subsequently, the GDG determined that recent evidence demonstrating a significant increase in CRC incidence among individuals younger than 55 years, which was attributable to a strong birth-cohort effect,3 warranted a reevaluation of the optimal age to start screening in the average-risk population. Additional modeling analyses by the MISCAN investigators incorporated recent Surveillance, Epidemiology, and End Results (SEER) incidence data and evaluated screening outcomes for the general US population.34 Analyses of outcomes for race-specific and sexspecific groups by MISCAN and SimCRC, which initially were carried out under the assumption of stable incidence, were repeated to incorporate recent SEER incidence data.33 Under the direction of the GDG, the ACS staff performed a supplemental literature review to examine differential risk and screening outcomes in racial and ethnic subgroups. In addition, literature searches were conducted to identify relevant new studies that have addressed screening outcomes since completion of the USPSTF evidence review. The GDG also examined data provided by the ACS Surveillance and Health Services Research Program on disease burden using data from the SEER program.35 Unless otherwise indicated, all incidence and mortality rates are per 100,000 person-years and age-adjusted to the US standard population. While the primary source of evidence for this guideline used a different rating system for the appraisal of evidence,26, 29 the GDG applied the principles of the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) and GRADE Evidence-to-Decision (EtD) frameworks in formulating and assigning the strength of recommendations.36, 37 The principal GRADE decision-making criteria are: 1) balance between desirable and undesirable effects—the greater the difference between desirable and undesirable effects, the higher the likelihood that a strong recommendation is warranted, and the narrower the difference, the higher the likelihood that a qualified recommendation is warranted; 2) quality of evidence—the higher the quality of evidence, the higher the likelihood that a strong recommendation is warranted; and 3) values and preferences—the greater the uniformity or certainty in values and preferences, the higher the likelihood that a strong recommendation is warranted. Each recommendation was designated by the GDG as either strong or qualified, in accordance with GRADE guidance.38 A strong recommendation conveys the consensus that the benefits of adherence to the intervention outweigh the undesirable effects and that most patients would choose the intervention. A qualified recommendation indicates there is clear evidence of benefit (or harm) but less certainty either about the balance of benefits and harms or about patients’ values and preferences, which could lead to different individual decisions. Additional elements included in the GRADE EtD framework and considered in this guideline are the impact on health equity, feasibility, and acceptability.37 The ACS does not apply cost and resource use as a decision-making criterion for recommendations. Actual costs of CRC screening tests and follow-up examinations vary widely in the United States, and costs, coverage, and reimbursement may be important considerations for individuals when making decisions about screening tests (see Patient considerations of cost and reimbursement, below). Before final preparation of a manuscript for publication, the guideline was submitted to the ACS Mission Outcomes Committee and Board of Directors for review and approval of the proposed recommendations. The expert advisors and representatives from 30 relevant outside organizations were then invited to participate in an external review of the guideline. Responses were documented and reviewed by the GDG to determine whether modifications in the recommendations or narrative were warranted, and adopted changes were incorporated in the final manuscript.

Considerations in Developing Recommendations

Outcomes of Screening The GDG identified reduction in CRC mortality (measured as lifeyears gained [LYGs] in the modeling reports) and incidence as the principal benefits of screening. Although the previous ACS guideline gave priority to CRC incidence reduction, in this update, the GDG did not prioritize incidence reduction over mortality reduction. There is variability in prevention potential among the available screening tests, but all noncolonoscopy screening tests contribute to prevention through colonoscopy follow-up and adenoma removal after a positive initial screening test, as demonstrated by the reduction in incidence in the US guaiac fecal occult blood test (gFOBT) randomized trial.39 Although prevention is highly valued by patients, test preparation, invasiveness, potential costs, and other considerations will lead some patients to prefer a noncolonoscopy test for screening. Greater value was placed on the role of patient preferences and on the potential to increase CRC screening utilization through offering choice in screening test options. The GDG recognized the potential relevance of other beneficial outcomes, including reduction of disease and treatment morbidity and improved quality of life, but identified no studies that demonstrated direct associations with screening. The principal recognized harms of CRC screening, which are rare, are those associated with colonoscopy (bleeding, perforation, cardiorespiratory complications of sedation) as a primary screening test or as a follow-up of other positive noncolonoscopy tests.26, 40, 41 The harm conventionally associated with workup of false-positive test results is partly mitigated when a normal follow-up examination removes the patient from the screening pool for 10 years. In addition to estimating the number of colonoscopy-related complications, the CISNET modeling group used the number of colonoscopies required as a proxy for harms and a measure of the burden of CRC screening.30 The GDG regarded the number of colonoscopies (and related risk of complications) as a proxy for harms. Individual patient burden was considered primarily in the context of patient decision making on the basis of test attributes. For computed tomography colonography (CTC), attention was given to additional potential harms associated with radiation exposure and workup of incidental findings not leading to residual benefit. Screening test performance measures (sensitivity, specificity, etc) were included as important outcomes in evaluating the evidence on screening tests. Relatively low importance was ascribed to the beneficial effect of reassurance from a negative screening test as well as to the burden of anxiety precipitated by a false-positive test result. Evidence-Based Inferential Reasoning Results from randomized controlled trials (RCTs) of CRC screening with either a stool-based test (gFOBT) or a structural examination (flexible sigmoidoscopy [FS]) have demonstrated mortality reductions associated with the detection of advanced neoplasia in asymptomatic adults.26 The evidence of benefit for all other screening tests is limited to test performance data demonstrating the ability to detect early stage CRC and/or advanced adenomas and observational studies. In addition to this body of evidence for the individual modalities, the GDG adopted evidence-based inferential reasoning to extrapolate from the evidence establishing a rationale for using the detection of occult blood as an effective screening tool to support fecal immunochemical testing (FIT) and multitarget stool DNA (mt-sDNA) testing, which includes multiple molecular assays combined with a hemoglobin immunoassay. Similarly, findings from RCTs of FS provide a compelling “proof of concept” for structural evaluation of the colon to detect both CRC and adenomas as an effective approach to reducing CRC incidence and mortality. In addition to examining the test performance and observational data on the other 2 currently available structural examinations (colonoscopy and CTC), the GDG made the judgment to extrapolate the RCT evidence on FS. Use of Modeling Studies Given the limited evidence on long-term outcomes for the different screening options as well as direct comparisons, modeling studies have been used to compare the potential effectiveness of different screening strategies, and the results of these studies have influenced the USPSTF CRC screening recommendations.30, 42-44 The CISNET investigators have devised a methodology to identify model-recommended screening strategies for consideration among the numerous unique strategies that are generated by combinations of tests with different starting and stopping ages and screening intervals. Model-recommended screening strategies for individual tests are based on the balance of benefits, expressed as LYGs (corrected for life-years lost because of screening complications) versus burden and harms, expressed as the number of colonoscopies required for a given strategy (screening, follow-up, surveillance, and diagnosis of symptomatic cancer). The burden of noncolonoscopy tests is addressed by grouping and comparing screening options that have similar test characteristics, resulting in 4 separate classes of screening tests (ie, colonoscopy, all stool tests, FS, and CTC). Strategies within each class that achieve the highest LYGs for a given number of colonoscopies are deemed efficient, whereas strategies that achieve at least 98% of the highest LYGs are deemed “near-efficient.” For all efficient and near-efficient strategies, an efficiency ratio (ER) is estimated, which is a measure of burden to benefit based on the ratio of the incremental number of colonoscopies divided by the incremental number of LYGs compared with the nearest less effective efficient strategy. From the efficient or near-efficient strategies in each class, modelrecommendable strategies are those that have an acceptable overall benefit and ER (balance of burden to benefit).33, 34 The limitations of modeling arise from the uncertainty inherent in the parameters and assumptions that underpin the model inputs. One such assumption in the CISNET models30, 31 is 100% adherence to all screening strategies, including 100% adherence to follow-up colonoscopy for positive initial noncolonoscopic screening examinations. The assumption of full adherence allows for comparison of the screening options under a uniform scenario. However, actual screening and follow-up adherence rates vary by test, setting, and population group, meaning that actual outcomes could diverge from predicted outcomes based on differential uptake and follow-up. These limitations are acknowledged by the CISNET investigators and were acknowledged by the GDG in integrating modeling results with empirical evidence. Patient Preferences, Choice, and Adherence CRC screening presents a unique challenge and opportunity, as there are multiple screening tests with variability in supporting evidence of effectiveness, risk of harm, prevention potential, and patient burden. There is no consistent, direct evidence that adults prefer any one CRC screening tool or strategy over others. Individual preferences can be influenced by patient education about screening, test characteristics (ie, accuracy, degree of invasiveness, test preparation, required screening interval, and cost), and clinician recommendation.45-50 The ACS is committed to increasing utilization to achieve the benefits of CRC screening by recommending that patients be given an opportunity to choose a testing strategy, thus increasing the likelihood of adherence. Patient preference is an important consideration, although the choice of test must be predicated on high-quality screening test options that are accessible to the patient, and there must be access to follow-up colonoscopy if needed.


The ACS recommends that adults aged 45 years and older with an average risk of colorectal cancer undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation (Table 1). Table 1. American Cancer Society Guideline for CRC Screening, 2018