Dataset Information

Emerging Tests for Noninvasive Colorectal Cancer Screening.

ABSTRACT: Colorectal cancer (CRC) is among the most common cancers globally and a major cause of cancer-related deaths. The American Cancer Society estimates that CRC will kill 1 in 60 Americans, and CRC screening is recommended for all Americans ≥45 years of age. Current CRC screening methods are effective for preventing CRC and have been shown to reduce CRC-related mortality. However, none of the currently available tests is ideal, and many people are not compliant with screening recommendations. Novel screening tests based on advances in CRC molecular biology, genetics, and epigenetics, combined with developments in sequencing technologies and computational analytic methods, have been developed to address the shortcomings of current CRC screening tests. These emerging tests include blood-based assays that use plasma-derived circulating tumor DNA and serum proteins to detect early CRC and advanced adenomas, assays that use stool DNA or mRNA, and methods for profiling the gut microbiome. Here we review current screening modalities, and we discuss the principles behind the most promising emerging CRC screening tests and the data supporting their potential to be used in clinical practice.

SUBMITTER: Hanna M

PROVIDER: S-EPMC9974876 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Emerging Tests for Noninvasive Colorectal Cancer Screening.

Hanna Marina M Dey Neelendu N Grady William M WM

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20221217 3

Colorectal cancer (CRC) is among the most common cancers globally and a major cause of cancer-related deaths. The American Cancer Society estimates that CRC will kill 1 in 60 Americans, and CRC screening is recommended for all Americans ≥45 years of age. Current CRC screening methods are effective for preventing CRC and have been shown to reduce CRC-related mortality. However, none of the currently available tests is ideal, and many people are not compliant with screening recommendations. Novel ...[more]

PMID: 36539002

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Project description:Background & aimsBiomarker assays could increase the accuracy of noninvasive detection of colorectal cancer (CRC); fecal immunochemical tests (FITs) are estimated to miss 27%-47% of CRCs and 70%-80% of advanced adenomas per round of screening. We investigated the conditions under which biomarker screens would be cost-effective compared with FIT screens of average-risk individuals.MethodsWe used the MISCAN-Colon microsimulation model to estimate the effects of various CRC screening test characteristics on life-years gained (LYG) and; age-specific all-cause mortality was based on the 2010 Dutch life tables. Simulated CRC incidence rate and CRC stage distribution were calibrated to observed data in The Netherlands from 1999 through 2003 (before opportunities for screening). Survival rates after diagnosis of CRC at an age younger than 75 years were based on CRC relative survival data from 1985 through 2004; survival for individuals diagnosed at an age of 75 years or older was adjusted to fit the observed age-increasing mortality/incidence ratio. We modeled FIT along with hypothetical biomarker tests with different test performance levels. For each biomarker test we calculated the maximum unit cost for the test to be cost-effective compared with FIT, assuming a willingness-to-pay threshold of €50,000 ($56,000) per LYG.ResultsBiennial FIT screening of subjects 55-75 years old provided 84.9 LYG at a cost of €122,000 ($137,000) per 1000 participants. Considering a unit cost of €7 ($8) for FIT (including kit and analysis only, excluding organizational costs), a biomarker test that detects CRC with higher levels of specificity and sensitivity (100%) and advanced adenomas at a proportionally higher level of sensitivity (53%) should never exceed a cost of €51 ($57). The threshold cost could increase to more than €200 ($224) for high-performing biomarker tests in cases of limited colonoscopy capacity or higher uptake of this test.ConclusionsBy using the MISCAN-Colon microsimulation model to estimate effects of CRC screening tests, we found that for a biomarker test with increased overall performance to be cost-effective, it should not exceed 7-fold the unit cost of FIT. This maximum would increase substantially if colonoscopy becomes more expensive or scarce, or if the new test has higher screening uptake. These values could be used to estimate the added value of new biomarkers compared with current FIT screening.

Project description:BackgroundHealthcare is a major contributor to global greenhouse gas emissions. Colorectal cancer (CRC) screening is one of the most widely used healthcare services in the US, indicated for approximately 134 million adults. Recommended screening options include fecal immunochemical tests (FITs) every year, CT colonographies (CTCs) every 5 years, or colonoscopies every 10 years. We compared the environmental impacts of these tests and identified opportunities for impact reduction.MethodsWe conducted a comparative life cycle assessment of three CRC screening strategies at the University of California, San Francisco. We performed on site audits to document the materials and energy used for each screening test. We used the ReCiPe 2016 method to estimate the environmental impacts of these procedures, measured by global warming potential (GWP) and damage to human health. We estimated the 10-year cumulative impacts of each screening strategy using a Markov reward model. We accounted for model uncertainty using hierarchical Monte Carlo simulations.FindingsFIT-based screening had the lowest environmental impacts, with a roughly 20% margin of superiority over colonoscopies, and this finding was robust in sensitivity analyses. Across tests, the biggest cause of environmental harm was car-based transportation of patients and staff. Prioritizing FITs over screening colonoscopies in the US could enhance population health by roughly 5.2 million disability adjusted life years per decade. Transitioning to electric vehicles could reduce the GWP of all screening tests by 15-20%.InterpretationGiven the similar efficacy and safety of these tests, payors should prioritize FITs for low-risk patients. Government initiatives to decarbonize transportation, incentivize telehealth, and mandate environmental product declarations will help reduce the environmental impacts of healthcare more generally. Our results call for a closer look at resource-intensive preventative health strategies, which could result in more harm than good if applied to a low-risk population.FundingNIH, UCSF.

Project description:BackgroundColorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications.Main resultsRecently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection.ConclusionHere, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.

Dataset Information

Emerging Tests for Noninvasive Colorectal Cancer Screening.

Publications

Emerging Tests for Noninvasive Colorectal Cancer Screening.

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