Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation. METHODS: Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMSmin) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses. RESULTS: CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation. CONCLUSIONS: CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.

Enrollee characteristics and receipt of colorectal cancer testing in Pennsylvania after adoption of the Affordable Care Act Medicaid expansion.

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer-related death in the U.S. Despite increased CRC screening rates, they remain low among low-income non-older adults, including Medicaid enrollees who are more likely to be diagnosed at advanced stages. OBJECTIVES: Given limited evidence regarding CRC screening service use among Medicaid enrollees, we examined multilevel factors associated with CRC testing among Medicaid enrollees in Pennsylvania after Medicaid expansion in 2015. RESEARCH DESIGN: Using the 2014-2019 Medicaid administrative data, we performed multivariable logistic regression models to assess factors associated with CRC testing, adjusting for enrollment length and primary care services use. SUBJECTS: We identified 15,439 adults aged 50-64 years newly enrolled through Medicaid expansion. MEASURES: Outcome measures include receiving any CRC testing and by modality. RESULTS: About 32% of our study population received any CRC testing. Significant predictors for any CRC testing include being male, being Hispanic, having any chronic conditions, using primary care services ≤4 times annually, and having a higher county-level median household income. Being 60-64 years at enrollment, using primary care services >4 times annually, and having higher county-level unemployment rates were significantly associated with a decreased likelihood of receiving any CRC tests. CONCLUSIONS: CRC testing rates were low among adults newly enrolled in Medicaid under the Medicaid expansion in Pennsylvania relative to adults with high income. We observed different sets of significant factors associated with CRC testing by modality. Our findings underscore the urgency to tailor strategies by patients' racial, geographic, and clinical conditions for CRC screening.

Counting Advanced Precancerous Lesions as True Positives When Determining Colorectal Cancer Screening Test Specificity.

The landmark Centers for Medicare & Medicaid Services (CMS) decision memo on blood-based biomarkers to screen for colorectal cancer (CRC) sets thresholds of 74% or higher for sensitivity and 90% or higher for specificity for CRC. This approach does not consider detection of advanced precancerous lesions as true positives. We contrasted the impact of counting advanced precancerous lesions as true vs false positives and projected CRC outcomes under contrasting tests in a validated model. A test with the threshold performance set by CMS decreased CRC incidence by 30% and CRC mortality by 48% in individuals aged 45 years. If this test also detected advanced precancerous lesions with 30% sensitivity, CRC incidence decreased by 45% and mortality by 58%, but the CRC specificity of the test of only 88% would not satisfy the CMS threshold. CMS should reconsider its definition of threshold specificity for CRC screening biomarkers. Future coverage determinations on biomarkers to screen for cancer should consider detection of relevant precursor lesions and projected outcomes.

Sex differences in the impact of Affordable Care Act Medicaid expansion on colorectal cancer screening.

Access to care varies by sex such that interactions with insurance status result in mixed patterns of preventive services utilization. We examined sex-specific effects of ACA Medicaid expansions on receipt of CRC screening. We used Behavioral Risk Factor Surveillance System data (2008-2016) for adults aged 50-64 years with household income ≤138% of federal poverty level to examine self-reported lifetime use of guideline-recommended CRC screening services overall and by screening modality. We employed difference-in-difference models comparing changes in CRC screening in 20 Medicaid expansion states before and after the ACA to changes in 18 states that did not expand Medicaid during our study period. We divided the expansion period into implementation (2014) and post-expansion (2016) periods to account for possible lagged effects. We observed time-varying effects of Medicaid expansion that revealed relative increases in CRC screening occurring during the post-expansion period. Heterogeneous effects by sex and by screening modality were also observed: there was a significant relative increase of 16.2 percentage points (95% CI [2.2, 30.2]; p-value = 0.023) in lifetime colonoscopy use among women in expansion states relative to non-expansion states in the post-expansion period. There were no significant effects of Medicaid expansion among men. Health insurance expansion had a lagged but significant effect on CRC screening among low-income non-elderly women in Medicaid expansion states, but no effect for men. The observed increase in CRC screening among women suggests that barriers to CRC screening may differ by sex, and tailored interventions to increase CRC screening improve outcomes.

Strategies for Colorectal Cancer Screening.

The incidence of colorectal cancer (CRC) is increasing worldwide. CRC has high mortality when detected at advanced stages, yet it is also highly preventable. Given the difficulties in implementing major lifestyle changes or widespread primary prevention strategies to decrease CRC risk, screening is the most powerful public health tool to reduce mortality. Screening methods are effective but have limitations. Furthermore, many screen-eligible people remain unscreened. We discuss established and emerging screening methods, and potential strategies to address current limitations in CRC screening. A quantum step in CRC prevention might come with the development of new screening strategies, but great gains can be made by deploying the available CRC screening modalities in ways that optimize outcomes while making judicious use of resources.

Cost-Effectiveness and National Effects of Initiating Colorectal Cancer Screening for Average-Risk Persons at Age 45 Years Instead of 50 Years.

BACKGROUND & AIMS: The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. METHODS: We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. RESULTS: Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13-14 CRC cases and 6-7 CRC deaths and gained 27-28 discounted QALYs while saving $163,700-$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50-75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. CONCLUSIONS: In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons.

Detection and localization of surgically resectable cancers with a multi-analyte blood test.

Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

Telephone Encounters Predict Future High Financial Expenditures in Inflammatory Bowel Disease Patients: A 3-Year Prospective Observational Study.

BACKGROUND: Telephone activity is essential in management of complex chronic diseases including inflammatory bowel disease (IBD). Telephone encounters logged in the electronic medical record have recently been proposed as a surrogate marker of disease activity and impending health care utilization; however, the association between telephone calls and financial expenditures has not been evaluated. STUDY: We performed a 3-year prospective observational study of telephone encounters logged at a tertiary referral IBD center. We analyzed patient demographics, disease characteristics, comorbidities, clinical activity, and health care financial charges by telephone encounter frequency. RESULTS: Eight hundred one patients met inclusion criteria (52.3% female; mean age, 44.1 y), accounted for 12,669 telephone encounters, and accrued $70,513,449 in charges over 3 years. High telephone encounter frequency was associated with female gender (P=0.003), anxiety/depression (P<0.001), and prior IBD surgery (P<0.001). High telephone encounter categories had significantly more hospitalizations (P<0.001), IBD surgery (P<0.001), worse quality of life (P<0.001), more corticosteroid (P<0.001), biological (P<0.001), and opiate prescriptions (P<0.001). High telephone encounter frequency patients amassed higher total available charges in each year (P<0.001) and over the 3 years (P<0.001). Telephone encounters in 2009 (P=0.02) and 2010 (P<0.001) were significantly associated with financial charges the following year after controlling for demographic, utilization, and medication covariates. CONCLUSIONS: Increased telephone encounters are associated with significantly higher health care utilization and financial expenditures. Increased call frequency is predictive of future health care spending. Telephone encounters are a useful tool to identify patients at risk of clinical deterioration and large financial expense.

Physicians encouraging colorectal screening: a randomized controlled trial of enhanced office and patient management on compliance with colorectal cancer screening.

BACKGROUND: Colorectal cancer screening is underused. Our objective was to evaluate methods for promoting colorectal cancer screening in primary care practice. METHODS: A 2 x 2 factorial randomized clinical trial measured the effects of a tailored vs nontailored physician recommendation letter and an enhanced vs nonenhanced physician office and patient management intervention on colorectal cancer screening adherence. The enhanced and nonenhanced physician office and patient management interventions varied the amount of external support to help physician offices develop and implement colorectal cancer screening programs. The study included 10 primary care physician office practices and 599 screen-eligible patients aged 50 to 79 years. The primary end point was medical-record-verified flexible sigmoidoscopy or colonoscopy. Statistical end-point analysis (according to randomization intent) used generalized estimating equations to account for correlated outcomes according to physician group. RESULTS: During a 1-year period, endoscopy in the lower gastrointestinal tract (lower endoscopy) occurred in 289 of 599 patients (48.2%). This finding included the following rates of lower endoscopy: 81 of 152 patients (53.3%) in the group that received the tailored letter and enhanced management; 103 of 190 (54.2%) in the group that received the nontailored letter and enhanced management; 58 of 133 (43.6%) in the group that received the tailored letter and nonenhanced management; and 47 of 124 (37.9%) in the group that received the nontailored letter and nonenhanced management. Enhanced office and patient management increased the odds of completing a colonoscopy or flexible sigmoidoscopy by 1.63-fold (95% confidence interval, 1.11-2.41; P = .01). However, the tailored letter increased the odds of completion by only 1.08-fold (95% confidence interval, 0.72-1.62; P = .71). CONCLUSIONS: Approximately one-half of the screen-eligible primary medical care patients aged 50 to 79 years obtained lower endoscopic colorectal cancer screening within 1 year of recommendation. An enhanced office and patient management system significantly improved colorectal cancer screening adherence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00327457.

The management of small polyps found by virtual colonoscopy: results of a decision analysis.

BACKGROUND & AIMS: There is a firm consensus that larger (> or =10 mm) colonic polyps should be removed; however, the importance of removing smaller polyps (<10 mm) is more controversial. If computed tomographic colonography (CTC) is used for colorectal cancer screening, the majority of polypoid lesions identified will be less than 10 mm in size. Decision-analytic techniques were used to compare the outcomes of 2 management strategies for smaller (6-9 mm) polyps discovered by CTC. METHODS: Hypothetic average-risk patients who had undergone a CTC examination and found to have a small (6-9 mm) polyp were simulated to either: (1) undergo immediate colonoscopy for polypectomy (COLO), or (2) wait 3 years for a repeat CTC examination (WAIT). A Markov model was constructed to analyze outcomes including the number of deaths and cancers after a 3-year follow-up period or time horizon. Values for the model parameters were derived from the published literature and from Surveillance Epidemiology and End Results data, and an extensive sensitivity analysis was performed. RESULTS: The COLO strategy resulted in 14 total deaths per 100,000 patients compared with 79 total deaths in the WAIT strategy, for a difference of 65 deaths. The COLO strategy resulted in 39 cancers per 100,000 patients vs 773 in the WAIT strategy, for a difference of 734 cancers. Sensitivity analysis found that model findings were robust and only sensitive at extreme parameter values. CONCLUSIONS: Managing smaller polyps detected on a screening CTC with another CTC examination 3 years later likely will result in more deaths and cancers than immediate colonoscopy and polypectomy.

The case for population-based screening for colorectal cancer.

Screening for colorectal cancer is commanding increasing attention. Other cancer screening programmes have been a part of public consciousness for some time, but, until recently, colorectal cancer screening has remained in the background. Fuelled by new research, market opportunities and increased recognition of individual risk, screening for colorectal cancer is becoming a recommended procedure, but controversy about how best to implement widespread screening remains.