Search

Background: Aspirin may decrease colorectal cancer incidence, but its role as an adjunct to or substitute for screening has not been evaluated.Objective: To examine the potential cost-effectiveness of aspirin chemoprophylaxis in relation to screening.Design: Markov model.Data Sources: Literature on colorectal cancer epidemiology, screening, costs, and aspirin chemoprevention (1980-1999).Target Population: General U.S. population.Time Horizon: 50 to 80 years of age.Perspective: Third-party payer.Intervention: Aspirin therapy in patients screened with sigmoidoscopy every 5 years and fecal occult blood testing every year (FS/FOBT) or colonoscopy every 10 years (COLO).Outcome Measures: Discounted cost per life-year gained.Results Of Base-case Analysis: When a 30% reduction in colorectal cancer risk was assumed, aspirin increased costs and decreased life-years because of related complications as an adjunct to FS/FOBT and cost $149 161 per life-year gained as an adjunct to COLO. In patients already taking aspirin, screening with FS/FOBT or COLO cost less than $31 000 per life-year gained.Results Of Sensitivity Analysis: Cost-effectiveness estimates depended highly on the magnitude of colorectal cancer risk reduction with aspirin, aspirin-related complication rates, and the screening adherence rate in the population. However, when the model's inputs were varied over wide ranges, aspirin chemoprophylaxis remained generally non-cost-effective for patients who adhere to screening.Conclusions: In patients undergoing colorectal cancer screening, aspirin use should not be based on potential chemoprevention. Aspirin chemoprophylaxis alone cannot be considered a substitute for colorectal cancer screening. Public policy should focus on improving screening adherence, even in patients who are already taking aspirin. [ABSTRACT FROM AUTHOR]

Background: Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine.Objective: To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives.Design: Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers.Data Sources: Published literature.Target Population: All persons with newly diagnosed colorectal cancer and their relatives.Time Horizon: Lifetime.Perspective: Third-party payer.Intervention: Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery.Outcome Measures: Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios.Results Of Base-case Analysis: The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36,200 per life-year gained.Results Of Sensitivity Analysis: The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50,000 per life-year gained. Immunohistochemistry followed by BRAF mutation testing was preferred in 59% of iterations in probabilistic sensitivity analysis at a threshold of $100,000 per life-year gained. Screening for the Lynch syndrome with immunohistochemistry followed by BRAF mutation testing only up to age 70 years cost $44,000 per incremental life-year gained compared with screening only up to age 60 years, and screening without an upper age limit cost $88,700 per incremental life-year gained compared with screening only up to age 70 years.Limitation: Other types of cancer, uncertain family pedigrees, and genetic variants of unknown significance were not considered.Conclusion: Widespread colorectal tumor testing to identify families with the Lynch syndrome could yield substantial benefits at acceptable costs, particularly for women with a mutation associated with the Lynch syndrome who begin regular screening and have risk-reducing surgery. The cost-effectiveness of such testing depends on the participation rate among relatives at risk for the Lynch syndrome.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: Cell-free DNA blood tests (cf-bDNA) and next-generation stool tests could change colorectal cancer (CRC) screening., Objective: To estimate the clinical and economic impacts of novel CRC screening tests., Design: Cost-effectiveness analysis using MOSAIC (Model of Screening and Surveillance for Colorectal Cancer)., Data Sources: Published data., Target Population: Average-risk persons., Time Horizon: Ages 45 to 100 years., Perspective: Health sector., Intervention: Novel versus established CRC screening tests., Outcome Measures: Incidence and mortality of CRC, quality-adjusted life-years (QALYs), costs., Results of Base-Case Analysis: For colonoscopy every 10 years, annual fecal immunochemical test (FIT), and triennial next-generation multitarget stool DNA, FIT-RNA, cf-bDNA (Guardant Shield), or cf-bDNA (Freenome), the relative rates (RRs) and 95% uncertainty intervals (UIs) versus no screening for CRC incidence were 0.21 (0.19 to 0.22), 0.29 (0.27 to 0.31), 0.33 (0.32 to 0.36), 0.32 (0.30 to 0.34), 0.58 (0.55 to 0.61) and 0.58 (0.55 to 0.60), respectively; the RRs for CRC death were 0.19 (0.17 to 0.20), 0.25 (0.23 to 0.27), 0.28 (0.27 to 0.30), 0.28 (0.26 to 0.30), 0.44 (0.42 to 0.47), and 0.46 (0.44 to 0.49), respectively. The cf-bDNA test (Shield; list price $1495) cost $89 600 ($74 800 to $102 300) per QALY gained versus no screening; alternatives were less costly and more effective., Results of Sensitivity Analysis: Incremental costs exceeded incremental benefits when novel test intervals were shortened to 2 or 1 years. The cf-bDNA test matched FIT's impact on CRC mortality at 1.35 (1.30 to 1.40)-fold FIT's uptake rate, assuming equal colonoscopy follow-up. If persons who accept colonoscopy or stool tests shifted to cf-bDNA, CRC deaths increased. This adverse effect was overcome if every 3 such substitutions were counterbalanced by cf-bDNA uptake by 2 or more persons refusing alternatives, assuming equal colonoscopy follow-up., Limitation: Longitudinal test-specific participation patterns are unknown., Conclusion: First-generation cf-bDNA tests may deliver net benefit or harm, depending on the balance between achieving screening in persons who decline alternatives versus substituting cf-bDNA for more effective alternatives., Primary Funding Source: The Gorrindo Family Fund., Competing Interests: Disclosures: Disclosure forms are available with the article online.

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.

Background: Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied., Objective: To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors., Design: Retrospective cohort study., Setting: A large, diverse, community-based health care system., Participants: 3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016., Measurements: Diagnostic yield of different LS screening strategies., Results: Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC., Limitation: Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics., Conclusion: The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed., Primary Funding Source: Kaiser Permanente Northern California Division of Research.