Projected Colorectal Cancer Incidence and Mortality Based on Observed Adherence to Colonoscopy and Sequential Stool-Based Screening.

INTRODUCTION: Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening colonoscopy every 10 years vs annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data. METHODS: The MIcrosimulation SCreening ANalysis (MISCAN) model used observed sequential screening adherence, HSgFOBT positivity, and diagnostic colonoscopy adherence in HSgFOBT-positive individuals from the National Colonoscopy Study (single-screening colonoscopy vs ≥4 HSgFOBT sequential rounds). We compared CRC incidence and mortality over 15 years with no screening or 10 yearly screening colonoscopy vs annual HSgFOBT with 100% and differential observed adherence from the trial. RESULTS: Without screening, simulated incidence and mortality over 15 years were 20.9 (95% probability interval 15.8-26.9) and 6.9 (5.0-9.2) per 1,000 participants, respectively. In the case of 100% adherence, only screening colonoscopy was predicted to result in lower incidence; however, both tests lowered simulated mortality to a similar level (2.1 [1.6-2.9] for screening colonoscopy and 2.5 [1.8-3.4] for HSgFOBT). Observed adherence for screening colonoscopy (83.6%) was higher than observed sequential HSgFOBT adherence (73.1% first round; 49.1% by round 4), resulting in lower simulated incidence and mortality for screening colonoscopy (14.4 [10.8-18.5] and 2.9 [2.1-3.9], respectively) than HSgFOBT (20.8 [15.8-28.1] and 3.9 [2.9-5.4], respectively), despite a 91% adherence to diagnostic colonoscopy with FOBT positivity. The relative risk of CRC mortality for screening colonoscopy vs HSgFOBT was 0.75 (95% probability interval 0.68-0.80). Findings were similar in sensitivity analyses with alternative assumptions for repeat colonoscopy, test performance, risk, age, and projection horizon. DISCUSSION: Where sequential adherence to stool-based screening is suboptimal and colonoscopy is accessible and acceptable-as observed in the national colonoscopy study, microsimulation, comparative effectiveness, screening recommendations.

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. CONCLUSION: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Decreased colorectal cancer incidence and mortality in a diverse urban population with increased colonoscopy screening.

BACKGROUND: Although colorectal cancer screening has contributed to decreased incidence and mortality, disparities are present by race/ethnicity. The Citywide Colon Cancer Control Coalition (C5) and NYC Department of Health and Mental Hygiene (DOHMH) promoted screening colonoscopy from 2003 on, and hypothesized future reductions in CRC incidence, mortality and racial/ethnic disparities. METHODS: We assessed annual percent change (APC) in NYC CRC incidence, stage and mortality rates through 2016 in a longitudinal cross-sectional study of NY State Cancer Registry, NYC Vital Statistics, and NYC Community Health Survey (CHS) data. Linear regression tested associations between CRC mortality rates and risk factors. RESULTS: Overall CRC incidence rates from 2000 decreased 2.8% yearly from 54.1 to 37.3/100,000 population in 2016, and mortality rates from 2003 decreased 2.9% yearly from 21.0 to 13.9 in 2016 at similar rates for all racial/ethnic groups. Local stage disease decreased overall with a transient increase from 2002 to 2007. In 2016, CRC incidence was higher among Blacks (42.5 per 100,000) than Whites (38.0), Latinos (31.7) and Asians (30.0). In 2016, Blacks had higher mortality rates (17.9), than Whites (15.2), Latinos (10.4) and Asians (8.8). In 2016, colonoscopy rates among Blacks were 72.2%, Latinos 71.1%, Whites 67.2%, and Asians, 60.9%. CRC mortality rates varied by neighborhood and were independently associated with Black race, CRC risk factors and access to care. CONCLUSIONS: In a diverse urban population, a citywide campaign to increase screening colonoscopy was associated with decreased incidence and mortality among all ethnic/racial groups. Higher CRC burden among the Black population demonstrate more interventions are needed to improve equity.

Feasibility of Patient Navigation and Impact on Adherence to Screening Colonoscopy in a Large Diverse Urban Population.

INTRODUCTION: Disparities observed in colorectal cancer (CRC) incidence and mortality among blacks and Hispanics compared with whites may be in part due to lower screening rates. The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has implemented a patient navigator (PN) program at NYC hospitals serving lower-income patients to promote high adherence by patients referred for screening colonoscopy. A prior study showed this PN program increased adherence at 3 public hospitals. The aim of this study was to determine the feasibility of expanding the PN program to 10 hospital sites by assessing the impact of the PN program on adherence to screening colonoscopy in a large, urban, lower-income population. METHODS: Data were collected from 2007 through the first quarter of 2012 from PN sites. One site also contributed data from the pilot phase of the project, from 2005 to 2006. Adherence to scheduled screening colonoscopy among those ≥ 50 years was assessed among 10 hospital sites in NYC participating in the colonoscopy PN program. RESULTS: Among the 37,077 asymptomatic adults ≥ 50 years who were scheduled for a screening colonoscopy from 2005 to the first quarter of 2012, 84.2% (83.2% of black, 84.9% of Hispanic, and 87.5% of white adults) were adherent to scheduled colonoscopy. CONCLUSIONS: Expansion of PN programs to navigate all patients referred for a colonoscopy was feasible in a large, urban setting. This can be implemented resulting in high overall adherence rates to screening colonoscopies. The program likely did not result in large ethnic disparities.

High-Intensity Versus Low-Intensity Surveillance for Patients With Colorectal Adenomas: A Cost-Effectiveness Analysis.

Background: Surveillance of patients with colorectal adenomas has limited long-term evidence to support current practice. Objective: To compare the lifetime benefits and costs of high- versus low-intensity surveillance. Design: Microsimulation model. Data Sources: U.S. cancer registry, cost data, and published literature. Target Population: U.S. patients aged 50, 60, or 70 years with low-risk adenomas (LRAs) (1 to 2 small adenomas) or high-risk adenomas (HRAs) (3 to 10 small adenomas or ≥1 large adenoma) removed after screening with colonoscopy or fecal immunochemical testing (FIT). Time Horizon: Lifetime. Perspective: Societal. Intervention: No further screening or surveillance, routine screening after 10 years, low-intensity surveillance (10 years after LRA removal and 5 years after HRA removal), and high-intensity surveillance (5 years after LRA removal and 3 years after HRA removal). Outcome Measures: Colorectal cancer (CRC) incidence and incremental cost-effectiveness. Results of Base-Case Analysis: Without surveillance or screening, lifetime CRC incidence for patients aged 50 years was 10.9% after LRA removal and 17.2% after HRA removal at screening colonoscopy. Subsequent colonoscopic screening, low-intensity surveillance, or high-intensity surveillance decreased incidence by 39%, 46% to 48%, and 55% to 56%, respectively. Incidence of CRC and surveillance benefits were higher for adenomas detected at FIT screening and lower for older patients. High-intensity surveillance cost less than $30 000 per quality-adjusted life-year (QALY) gained compared with low-intensity surveillance. Results of Sensitivity Analysis: High-intensity surveillance cost less than $100 000 per QALY gained in most alternative scenarios for adenoma recurrence, CRC incidence, longevity, quality of life, screening ages, surveillance ages, test performance, disutilities, and cost. Limitation: Few surveillance outcome data exist. Conclusion: The model suggests that high-intensity surveillance as recommended in the United States provides modest but clinically relevant benefits over low-intensity surveillance at acceptable cost. Primary Funding Source: National Cancer Institute.

Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer.

BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion. CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach.

New York Citywide Colon Cancer Control Coalition: A public health effort to increase colon cancer screening and address health disparities.

BACKGROUND: Although screening for colorectal cancer (CRC) is a widely accepted concept nationally and screening rates are increasing, there are differences in screening rates between states and within states. METHODS: In an effort to increase screening rates and ensure equal access with respect to race/ethnicity, the New York City Department of Health and Mental Hygiene formed a coalition of stakeholders in 2003, with its primary focus on colonoscopy, to develop and implement strategies across the city to achieve this goal. RESULTS: From a screening colonoscopy rate of only 42% in 2003, these concerted efforts contributed to achieving a screening rate of 62% by 2007 and a screening rate of almost 70% in 2014 with the elimination of racial and ethnic disparities. CONCLUSIONS: This article provides details of how this program was successfully conceived, implemented, and sustained in the large urban population of New York City. The authors hope that by sharing the many elements involved and the lessons learned, they may help other communities to adapt these experiences to their own environments so that CRC screening rates can be maximized. Cancer 2016;122:269-277. © 2015 American Cancer Society.

Development and validation of a clinical score for predicting risk of adenoma at screening colonoscopy.

BACKGROUND: Currently, no clinical tools use demographic and risk factor information to predict the risk of finding an adenoma in individuals undergoing colon cancer screening. Such a tool would be valuable for identifying those who would most benefit from screening colonoscopy. METHODS: We used baseline data from men and women who underwent screening colonoscopy from the randomized, multicenter National Colonoscopy Study (NCS) to develop and validate an adenoma risk model. The study, conducted at three sites in the United States (Minneapolis, MN; Seattle, WA; and Shreveport, LA) asked all participants to complete baseline questionnaires on clinical risk factors and family history. Model parameters estimated from logistic regression yielded an area under the receiver operating characteristic curve (AUROCC) used to assess prediction. RESULTS: Five hundred forty-one subjects were included in the development model, and 1,334 in the validation of the risk score. Variables in the prediction of adenoma risk for colonoscopy screening were age (likelihood ratio test for overall contribution to model, P < 0.001), male sex (P < 0.001), body mass index (P < 0.001), family history of at least one first-degree relative with colorectal cancer (P = 0.036), and smoking history (P < 0.001). The adjusted AUROCC of 0.67 [95% confidence interval (CI), 0.61-0.74] for the derivation cohort was not statistically significantly different from that in the validation cohort. The adjusted AUROCC for the entire cohort was 0.64 (95% CI, 0.60-0.67). CONCLUSION: We developed and validated a simple well-calibrated risk score. IMPACT: This tool may be useful for estimating risk of adenomas in screening eligible men and women.