Average Risk For Colorectal Cancer Research Articles

Algorithm Development and Early Performance Evaluation of a Next-generation Multitarget Stool DNA Screening Test for Colorectal Cancer

Background and AimsThe multitarget stool DNA (mt-sDNA) assay is a non-invasive average-risk colorectal cancer (CRC) screening test. A new biomarker panel was developed for a next-generation test to improve specificity while maintaining/increasing sensitivity. We aimed first to establish an algorithm and cutoff for the next-generation mt-sDNA test and then to validate it using archived samples from the pivotal DeeP-C study (NCT01397747) of the first-generation test. MethodsAlgorithm development and cross-validation included 3011 samples from 2 specimen collection studies (NCT03821948, NCT03789162). The algorithm and cutoff were locked before validation. Validation test set samples included 57 CRC, 583 advanced precancerous lesions (APLs), and 7022 samples negative for CRC or APLs from the DeeP-C study, which prospectively enrolled average-risk, asymptomatic adults aged 50 to 84 years before screening colonoscopy. Next-generation biomarkers included methylated DNA markers LASS4, LRRC4, PPP2R5C, and ZDHHC1 (reference marker), and fecal hemoglobin. Primary validation endpoints were CRC sensitivity and specificity for the absence of advanced neoplasia. Secondary endpoints included APL sensitivity and specificity for non-neoplastic findings or negative colonoscopy. ResultsCross-validation and best-fit results from algorithm development closely matched, confirming algorithm reliability and reproducibility. For the test set, next-generation mt-sDNA test sensitivity was 93.0% (95% CI, 83.0%-98.1%) for CRC and 48.4% (95% CI, 44.2%-52.5%) for APLs. Specificity was 88.5% (95% CI, 87.7%-89.2%) for the absence of advanced neoplasia and 90.4% (95% CI, 89.5%-91.2%) for the combination of non-neoplastic findings or negative colonoscopy. ConclusionsBased on archived samples, the next-generation mt-sDNA test demonstrated promising CRC screening performance characteristics that will be further assessed in a prospective clinical validation study (BLUE-C; NCT04144738).

National Trends in the Incidence of Sporadic Malignant Colorectal Polyps in Young Patients (20-49 Years): An 18-Year SEER Database Analysis.

Background and Objectives: Conflicting guidelines exist for initiating average-risk colorectal cancer screening at the age of 45 years. The United States Preventive Services Task Force (USPSTF) changed its guidelines in 2021 to recommend initiating screening at 45 years due to an increasing incidence of young-onset colorectal cancer. However, the American College of Physicians (ACP) recently recommended not screening average-risk individuals between 45 and 49 years old. We aim to study the national trends in the incidence of sporadic malignant polyps (SMP) in patients from 20 to 49 years old. Materials and Methods: We analyzed the Surveillance, Epidemiology, and End Results database (2000-2017) on patients aged 20-49 years who underwent diagnostic colonoscopy with at least a single malignant sporadic colorectal polyp. Results: Of the 10,742 patients diagnosed with SMP, 42.9% were female. The mean age of incidence was 43.07 years (42.91-43.23, 95% CI). Approximately 50% of malignant polyps were diagnosed between 45 and 49 years of age, followed by 25-30% between 40 and 45. There was an upward trend in malignant polyps, with a decreased incidence of malignant villous adenomas and a rise in malignant adenomas and tubulovillous adenomas. Conclusions: Our findings suggest that almost half of the SMPs under 50 years occurred in individuals under age 45, younger than the current screening threshold recommended by the ACP. There has been an upward trend in malignant polyps in the last two decades. This reflects changes in tumor biology, and necessitates further research and support in the USPSTF guidelines to start screening at the age of 45 years.

Adenomas and Sessile Serrated Lesions in 45- to 49-Year-Old Individuals Undergoing Colonoscopy: A Systematic Review and Meta-Analysis.

Colorectal cancer (CRC) screening is now recommended at the age of 45 years in the United States. However, information regarding the adenomas detection rate (ADR) and sessile serrated lesions (SSLs) in 45- to 49-year-old individuals is limited. In addition, the impact of lowering the screening age to 45 years on the ADR and the detection rate of SSLs is not well elucidated. This systematic review and meta-analysis aims to report the overall ADR and SSL detection rate in 45- to 49-year-old individuals undergoing colonoscopy. We searched MEDLINE, EMBASE, SCOPUS, Web of Science, ClinicalTrials.gov , and the Cochrane database from inception through October 2022 to identify studies reporting on ADR and SSL detection rates in 45- to 49-year-old individuals undergoing colonoscopies for all indications. This approach acknowledges the possibility of including individuals undergoing diagnostic colonoscopies or those with increased risk factors for CRC. We also conducted a separate analysis examining ADR in average-risk individuals undergoing screening colonoscopy. The pooled rates with their corresponding 95% confidence intervals (CIs) were generated using the fixed-effects model. I2 was used to adjudicate heterogeneity. Sixteen studies met the inclusion criteria. All studies were retrospective except one; 3 had data from national/local registries. There were 41,709 adenomas detected across 150,436 colonoscopies. The pooled overall ADR was 23.1% (95% CI 19.7%-27.0%, I2 = 98.6%). The pooled ADR in individuals with average risk of CRC from 7 studies was 28.2% (95% CI 24.6%-32.0%, I2 = 96.5%). The pooled overall SSL detection rate from 6 studies was 6.3% (95% CI 3.8%-10.5%, I2 = 97%). The included studies were heterogeneous because of differences in the inclusion and exclusion criteria and patient population. In 45- to 49-year-old individuals undergoing a colonoscopy for any indication, the ADR and SSL detection rates were 23.1% and 6.3%, respectively. We conclude that these outcomes in 45- to 49-year-olds are comparable with individuals aged 50-54 years.

Commentary: Liquid Biopsy for Average-Risk Colorectal Cancer Screening

Commentary: Liquid Biopsy for Average-Risk Colorectal Cancer Screening

Would initiating colorectal cancer screening from age of 45 be cost-effective in Germany? An individual-level simulation analysis.

Colorectal cancer (CRC) screening has been shown to be effective and cost-saving. However, the trend of rising incidence of early-onset CRC challenges the current national screening program solely for people ≥50 years in Germany, where extending the screening to those 45-49 years might be justified. This study aims to evaluate the cost-effectiveness of CRC screening strategies starting at 45 years in Germany. DECAS, an individual-level simulation model accounting for both adenoma and serrated pathways of CRC development and validated with German CRC epidemiology and screening effects, was used for the cost-effectiveness analysis. Four CRC screening strategies starting at age 45, including 10-yearly colonoscopy (COL), annual/biennial fecal immunochemical test (FIT), or the combination of the two, were compared with the current screening offer starting at age 50 years in Germany. Three adherence scenarios were considered: perfect adherence, current adherence, and high screening adherence. For each strategy, a cohort of 100,000 individuals with average CRC risk was simulated from age 20 until 90 or death. Outcomes included CRC cases averted, prevented death, quality-adjusted life-years gained (QALYG), and total incremental costs considering both CRC treatment and screening costs. A 3% discount rate was applied and costs were in 2023 Euro. Initiating 10-yearly colonoscopy-only or combined FIT + COL strategies at age 45 resulted in incremental gains of 7-28 QALYs with incremental costs of €28,360-€71,759 per 1,000 individuals, compared to the current strategy. The ICER varied from €1,029 to €9,763 per QALYG, and the additional number needed for colonoscopy ranged from 129 to 885 per 1,000 individuals. Among the alternatives, a three times colonoscopy strategy starting at 45 years of age proves to be the most effective, while the FIT-only strategy was dominated by the currently implemented strategy. The findings remained consistent across probabilistic sensitivity analyses. The cost-effectiveness findings support initiating CRC screening at age 45 with either colonoscopy alone or combined with FIT, demonstrating substantial gains in quality-adjusted life-years with a modest increase in costs. Our findings emphasize the importance of implementing CRC screening 5 years earlier than the current practice to achieve more significant health and economic benefits.

Colorectal cancer screening uptake and adherence by modality at a large tertiary care center in the United States: a retrospective analysis

Objective Real-world data regarding colorectal cancer (CRC) screening adherence and use of various screening modalities is critical to improving efficacy of CRC prevention programs. We assessed overall CRC screening adherence rates and utilization by modality over a three-year period (2017-2019) within a large Primary Care network. Methods A retrospective review of individuals aged 50-75 years at average risk for CRC with at least one clinic visit in the previous 24 months. The primary outcome was CRC screening adherence each calendar year, overall and by modality, among the entire eligible population and among individuals newly completing screening (i.e., newly adherent). The final sample included 107,366 patients and 218,878 records. Results Overall CRC screening adherence increased from 2017 to 2019 (71% to 78%). Colonoscopy was the most utilized modality (up to approximately 74% were “up-to-date” with colonoscopy versus 4% for non-invasive options). However, utilization of various modalities accounting for individuals being “up-to-date” with screening changed over time, with the highest increase for mt-sDNA (10.2-fold increase), followed by FIT (1.6-fold increase) and colonoscopy (1.1-fold increase). Among newly adherent individuals, the proportion screened by colonoscopy and FOBT decreased (89% to 80% and 2.4% to 1.2%, respectively), while uptake of FIT and mt-sDNA increased (7.7% to 11.5% and 0.9% to 6.8%, respectively). Notably, FIT and mt-sDNA increased disproportionately among the age and race-ethnicity groups with the lowest overall screening rates. Conclusions In an opportunistic CRC screening program, adherence increased over time but remained below the national goal of 80%. Although colonoscopy remained the most utilized screening modality, colonoscopy uptake rates decreased, while utilization rates of mt-sDNA and FIT increased. Among minority populations, new uptake increased most with mt-sDNA and FIT. Multiple CRC screening options should be leveraged by patients and Providers to potentially improve the effectiveness and help address disparities in CRC prevention programs.

Colorectal cancer screening test exposure patterns in US adults 45 to 49 years of age, 2019-2021.

Several organizations now recommend that individuals at average risk for colorectal cancer (CRC) begin screening at 45 rather than 50 years of age. We present contemporary estimates of CRC screening in newly eligible adults aged 45 to 49 years between 2019 and 2021. Nationally representative prevalence estimates and population number screened were estimated based on the National Health Interview Survey. A logistic regression model assessed CRC screening prevalence differences by survey year and sociodemographic characteristics. In 2021, 19.7%-that is, fewer than 4 million of the eligible 19 million adults aged 45 to 49 years-were up-to-date on CRC screening. Screening was lowest in those who were uninsured (7.6%), had less than a high school diploma (15.4%), and Asian (13.1%). Additionally, fecal occult blood test and/or fecal immunochemical testing was underused, with only 2.4% (<460 000 people) reporting being up-to-date with screening usingthis modality in 2021. CRC screening in eligible young adults remains low. Concerted efforts to improve screening are warranted, particularly in underserved populations.

Cost-Effectiveness of Liquid Biopsy for Colorectal Cancer Screening in Patients Who Are Unscreened

Despite recommendations for universal screening, adherence to colorectal cancer screening in the US is approximately 60%. Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening. To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US. In this economic evaluation, a Markov model was developed to compare no screening and 5 colorectal cancer screening strategies: colonoscopy, liquid biopsy, liquid biopsy following nonadherence to colonoscopy, stool DNA, and fecal immunochemical test. Adherence to first-line screening with colonoscopy, stool DNA, or fecal immunochemical test was assumed to be 60.6%, and adherence for liquid biopsy was assumed to be 100%. For colonoscopy, stool DNA, and fecal immunochemical test, patients who did not adhere to testing were not offered other screening. In colonoscopy-liquid biopsy hybrid, liquid biopsy was second-line screening for those who deferred colonoscopy. Scenario analyses were performed to include the possibility of polyp detection for liquid biopsy. No screening, colonoscopy, fecal immunochemical test, stool DNA, liquid biopsy, and colonoscopy-liquid biopsy hybrid screening. Model outcomes included life expectancy, total cost, and incremental cost-effectiveness ratios. A strategy was considered cost-effective if it had an incremental cost-effectiveness ratio less than the US willingness-to-pay threshold of $100 000 per life-year gained. This study used a simulated cohort of patients aged 45 years with average risk of colorectal cancer. In the base case, colonoscopy was the preferred, or cost-effective, strategy with an incremental cost-effectiveness ratio of $28 071 per life-year gained. Colonoscopy-liquid biopsy hybrid had the greatest gain in life-years gained but had an incremental cost-effectiveness ratio of $377 538. Colonoscopy-liquid biopsy hybrid had a greater gain in life-years if liquid biopsy could detect polyps but remained too costly. In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid biopsy tests for colorectal cancer screening may become cost-effective if their cost is substantially lowered.

Patterns of colorectal cancer screening and adherence rates among an average-risk population enrolled in a national health insurance provider during 2009–2018 in the United States

While colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US), outcomes can be improved through timely screening. Despite the benefits and widespread availability of screening tests, adherence to recommended screening strategies is low. The study aimed to provide recent evidence regarding screening rates and adherence to screening recommendations among adults at average risk for CRC in a commercially insured and Medicare Advantage population. De-identified administrative data from a large US research database were examined to determine screening rates for the years 2009 through 2018. The study population included adults aged 50–75 years and annual study population counts ranged from 1,390,594 in 2009 to 1,654,544 in 2018. Incident screening rates were found to be relatively stable across the study years (approximately 15 %) with adherence lowest in the youngest age group (ages 50–54 years). Colonoscopies accounted for approximately 50 % of all screening tests performed, while there was a substantial increase in the use of home-based screening tests over the study timeframe. The use of the fecal immunochemical test increased from 17.2 % in 2009 to 28.9 % in 2018 and the multi-target stool DNA test increased from 0.4 % in 2015 to 9.0 % in 2018. Overall though, CRC screening and adherence rates remain relatively low among adults at average risk for CRC in the US. Improving adherence rates with CRC screening recommendations among individuals at average risk for CRC is required to improve health outcomes.

Personalized Initial Screening Age for Colorectal Cancer in Individuals at Average Risk

Colorectal cancer (CRC) risk varies widely in the population at average risk without a family history, but there are no established routines for translating this variation into personalized starting ages of screening. To illustrate derivation of risk-adapted starting ages of CRC screening based on the concept of risk advancement period (RAP) using sex and a polygenic risk score (PRS) as an example. This cohort study included participants in the UK Biobank study recruited in England, Wales, and Scotland between March 13, 2006, and October 1, 2010. Participants were aged 40 to 69 years, with no previous bowel cancer screening and no family history of CRC. Follow-up of cancer data was completed February 29, 2020, for England and Wales and January 31, 2021, for Scotland. The censoring date for death data was September 30, 2021, for England and Wales and October 31, 2021, for Scotland. Data on age, sex, and family history were collected at the baseline interview. A PRS was calculated based on 139 CRC-related risk loci. Hazard ratios (HRs) of sex and PRS with CRC risk and mortality were estimated using Cox proportional hazards regression models and were translated to RAPs to quantify how many years of age earlier or later men and individuals in higher or lower PRS deciles would reach risks comparable with those of the reference group (ie, women or those in the 5th and 6th PRS deciles). Among 242 779 participants (median age, 55 [IQR, 48-61] years; 55.7% women), 2714 incident CRC cases were identified during a median follow-up of 11.2 (IQR, 10.5-11.8) years and 758 deaths during a median follow-up of 12.8 (IQR, 12.0-13.4) years. The HRs of CRC risk were 1.57 (95% CI, 1.46-1.70) for men vs women and ranged from 0.51 (95% CI, 0.41-0.62) to 2.29 (95% CI, 2.01-2.62) across PRS deciles compared with the reference. The RAPs were 5.6 (95% CI, 4.6-6.6) years for men vs women and ranged from -8.4 (95% CI, -11.0 to -5.9) to 10.3 (95% CI, 8.5-12.1) years across PRS deciles compared with the reference deciles. Risk-adapted starting ages of screening would vary by 24 years between men in the highest PRS decile and women in the lowest PRS decile. Similar results were obtained regarding CRC mortality. In this large cohort study including women and men at average risk of CRC, risk-adapted starting ages of screening strongly varied by sex and a PRS. The RAP concept could easily accommodate additional factors for defining personalized starting ages of screening.

Effect of aspirin, warfarin, and proton-pump inhibitors on performance of fecal immunochemical test in colorectal cancer screening: a systematic review and meta-analysis.

This study aims to investigate the impact of antithrombotic agents and proton-pump inhibitors (PPIs) on fecal immunochemical test (FIT). PubMed, EMBASE, Web of Science, Cochrane Central, and Google Scholar were searched from inception until September 3, 2023. Studies comparing the diagnostic performance of FIT between medicine users and non-users in average-risk colorectal cancer screening populations were included. Pooled sensitivity, specificity, and positive predictive values (PPVs) for advanced neoplasia (AN) of FIT were compared by reporting pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model. Twenty-two studies enrolling 5,572,367 individuals were included. For aspirin, pooled sensitivity and specificity for AN were 57.2% and 88.4% in users versus 60.2% and 93.2% in non-users; while pooled ORs were 1.49 (95% CI 0.89-2.48, P = 0.13) and 0.72 (95% CI 0.62-0.83, P < 0.001), respectively. In subgroup analysis, there was no difference in sensitivity and specificity between the two groups at the cutoff of 20μg Hb/g (P = 0.57 and 0.29, respectively) but a significantly lower specificity in users compared with non-users at lower cutoffs (P < 0.001). Moreover, a significantly lower PPVAN in users compared with non-users was observed after matching age and sex confounders (P = 0.001). Warfarin had no significant influence on PPVAN of FIT (P = 0.43). PPIs were associated with a significantly lower PPVAN in users (P < 0.001). Aspirin use was associated with lower specificity and PPV of FIT. Aspirin discontinuation before FIT to reduce false-positive results should be interpreted with caution given concerns about cardiovascular events. Increasing cutoff values of FIT in aspirin users may be another possible approach. Additionally, warfarin withdrawal before FIT is unnecessary but PPIs withdrawal before FIT is recommended to reduce false-positive results.

The impact on clinical outcomes and healthcare resources from discontinuing colonoscopy surveillance subsequent to low-risk adenoma removal: A simulation study using the OncoSim-Colorectal model.

To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1-2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1-2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs.

The cost-effectiveness of non-invasive stool-based colorectal cancer screening offerings from age 45 for a commercial and medicare population

AimThe United States Preventive Services Taskforce (USPSTF) recently recommended lowering the age for average-risk colorectal cancer (CRC) screening from 50 to 45 years. While initiating screening at age 45 versus 50 provides a greater opportunity for CRC early detection and prevention, the full profile of benefits, risks, and cost-effectiveness of expanding the screen-eligible population requires further evaluation.Materials and methodsThe costs and clinical outcomes for screening at age 45 for triennial multi-target stool DNA [mt-sDNA], and other non-invasive stool-based modalities (annual fecal immunochemical test [FIT] and annual fecal-occult blood test [FOBT]), were estimated using the validated CRC-AIM microsimulation model over a lifetime horizon. Test sensitivity and specificity inputs were based on 2021 USPSTF modeling analyses; adherence rates were based on published real-world data and the costs of the screening test, follow-up colonoscopies, complications, and CRC care were included. Outcomes are reported from the perspective of a United States payer as clinical, life-years gained (LYG), and incremental cost-effectiveness ratio (ICER); stool-based and follow-up colonoscopy adherence ranges were explored in one-way, probabilistic and threshold analyses.ResultsWhen compared to initiation of CRC screening at age 45 versus 50, all modalities reduced both the incidence of and mortality from CRC and increased LYG. Initiating CRC screening at age 45 was cost-effective with an ICER of $59,816 and $35,857 per quality-adjusted life year (QALY) for mt-sDNA versus FIT and FOBT, respectively. In the threshold analyses, at equivalent rates to stool-based screening, mt-sDNA was always cost-effective at a willingness-to-pay threshold of $100,000 per QALY versus FIT and FOBT.ConclusionsInitiating average-risk CRC screening at age 45 instead of age 50 increases the estimated clinical benefit by reducing disease burden while remaining cost-effective. Among stool-based screening modalities, mt-sDNA provides the most clinical benefit in a Commercial and Medicare population.

Older Age at First Screening Colonoscopy is Associated With an Increased Risk of Colorectal Adenomas and Cancer.

The goal of colorectal cancer (CRC) screening is to detect precancerous polyps before cancer development or identification of cancer at an early stage. Guidelines have recommended screening colonoscopy to start at age 45. Our aim was to determine the impact of delays in performing the first screening colonoscopy on the risk of adenoma or CRC detection. We analyzed colonoscopy and histopathology data of average CRC risk patients who had their first screening colonoscopy between 2010 and 2017. Univariate and multivariable logistic regression was performed to determine the association between demographic variables and the risk of adenomas or CRC. A total of 1155 average risk patients underwent their initial screening colonoscopy during the study period. Median age was 54 years (range of 45-87) and 58.2% were females. In multivariable analysis, older age at first screening colonoscopy was significantly associated with the detection of adenomatous polyps (odds ratio 1.05, 95% confidence interval 1.04-1.07, P<0.001) and CRC (odds ratio 1.11, 95% confidence interval 1.06-1.16, P<0.001). The association between age and risk of adenomatous polyps (F-test 35.43, P=0.0019) and CRC (F-test 36.94, P=0.0017) fit an exponential growth model. It was estimated that the detection rate doubled every 14.20 years and 4.75 years for adenomas and CRC, respectively. We found that older age at the initial performance of a screening colonoscopy was associated with increased detection of adenomatous polyps and CRC. This work highlights the need for guideline adherence for the prevention of CRC development.

Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians (Version 2).

The purpose of this updated guidance statement is to guide clinicians on screening for colorectal cancer (CRC) in asymptomatic average-risk adults. The intended audience is all clinicians. The population is asymptomatic adults at average risk for CRC. This updated guidance statement was developed using recently published and critically appraised clinical guidelines from national guideline developers since the publication of the American College of Physicians' 2019 guidance statement, "Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults." The authors searched for national guidelines from the United States and other countries published in English using PubMed and the Guidelines International Network library from 1 January 2018 to 24 April 2023. The authors also searched for updates of guidelines included in the first version of our guidance statement. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to assess the quality of eligible guidelines. Two guidelines were selected for adoption and adaptation by raters on the basis of the highest average overall AGREE II quality scores. The evidence reviews and modeling studies for these 2 guidelines were also used to synthesize the evidence of diagnostic test accuracy, effectiveness, and harms of CRC screening interventions and to develop our guidance statements. Clinicians should start screening for colorectal cancer in asymptomatic average-risk adults at age 50 years. Clinicians should consider not screening asymptomatic average-risk adults between the ages of 45 to 49 years. Clinicians should discuss the uncertainty around benefits and harms of screening in this population. Clinicians should stop screening for colorectal cancer in asymptomatic average-risk adults older than 75 years or in asymptomatic average-risk adults with a life expectancy of 10 years or less. Clinicians should select a screening test for colorectal cancer in consultation with their patient based on a discussion of benefits, harms, costs, availability, frequency, and patient values and preferences. Clinicians should select among a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years as a screening test for colorectal cancer. Clinicians should not use stool DNA, computed tomography colonography, capsule endoscopy, urine, or serum screening tests for colorectal cancer.

A novel liquid biopsy methylation-based technology and early detection of colorectal cancer in patients.

e15527 Background: Since colorectal cancer (CRC) remains as the third most common and second most deadly malignant neoplasm, accurate and non-invasive detection technologies became a promising strategy to enhance early diagnosis. Our goal is to develop a liquid biopsy test able to detect methylation-based biomarkers in circulating tumor DNA (ct-DNA) collected from CRC patients' plasma. We are currently working on a digital PCR (dPCR)-based technology focused on detecting with high sensitivity and specificity our proprietary CRC specific epigenetic biomarker panel. Methods: We developed a bioinformatic platform that identifies methylation-based biomarkers from genome-wide Illumina 450K methylation data available in GDC-TCGA public databases. The platform uses multidimensional analysis algorithms and, through a predictive model, establishes a ranking with the most appropriate diagnostic epigenetic biomarkers. First, we tested the selected biomarkers in tumor tissue and in distant colonic mucosa from average risk CRC patients using qPCR. Then, ct-DNA from plasma samples of CRC patients and circulating DNA (cf-DNA) from risk matched negative colonoscopy-confirmed healthy individuals was analyzed by a novel dPCR-based technology in order to detect our panel of epigenetic biomarkers. Lastly, we applied a ROC analysis to the Area Under the Curve (AUC) values and obtained the corresponding sensitivity and specificity results. Results: Illumina 450K methylation data from primary tumor and normal tissue was incorporated into our bioinformatic platform that subsequently ranked 275 candidate genes. Based on several classification criteria we selected a panel composed of the three best ranked candidates. We validated the bioinformatic platform performance in identifying sensitive and specific CRC epigenetic biomarkers by detecting the presence of these biomarkers in tumor mucosa from paired CRC patients and its absence in distant colonic mucosa (n = 20) using qPCR. Furthermore, we applied our dPCR-based technology to simultaneously detect the three-gene panel of epigenetic biomarkers in ctDNA from 34 CRC patients and cfDNA from 33 healthy individuals. We obtained an overall AUC = 0.92, with 76% sensitivity (95% CI: 60-87%) and 90.9% specificity (95% CI: 76-97%). Conclusions: We validated a technology capable of detecting a novel and proprietary methylation-based biomarkers panel. This accurate liquid biopsy technology based on epigenetic biomarker detection applies dPCR and might be implemented in screening or early colorectal cancer detection. Although our technology needs further clinical validations and optimizations, we consider that the obtained results are strong enough to evolve in a complete epigenetic biomarker's blood-based test.

Screening for colorectal cancer : Arecommendation statement of the Austrian National Committee for Cancer Screening.

Colorectal cancer is the fourth most common cancer in Austria. To date, colorectal cancer screening in Austria remains opportunistic and includes colonoscopy or stool-based blood tests. The Austrian National Committee for Cancer Screening developed evidence-based recommendations for anationwide organized colorectal cancer screening program. The methodological framework followed the approach of the United States Preventive Services Task Force. The evidence base underlying the newly developed recommendations comprised areview of the existing published evidence and adecision analytic model tailored to the Austrian context. Using astructured process, committee members considered 1)the magnitude of the net benefit of each screening strategy, 2)the certainty of evidence, and 3)the level of acceptance of the interventions among the target population. The Austrian National Committee for Cancer Screening recommends the implementation of anationwide organized colorectal cancer screening program for all adults aged 45-75years. For persons 65years or older, screening decisions should occur on an individual basis in accordance with aperson's overall health, prior screening history, and preferences. Specifically, the committee recommends either a10-year screening colonoscopy or biennial fecal immunochemical tests with colonoscopy following apositive result, with both screening strategies considered equivalent. Each citizen should be able to make an informed decision about their preferred screening method. Switching between the two screening strategies should be possible. Following an unremarkable colonoscopy, screening by fecal immunochemical test (FIT) is only required after 10years. Screening recommendations apply only to asymptomatic persons at average risk for colorectal cancer. The screening program must be pilot tested, and accompanied by apublic information campaign, formative evaluation, quality assurance, and data collection.

Patient and provider factors associated with colorectal cancer screening among average risk health plan enrollees in the US, 2015–2018

BackgroundTo assess patient and primary care provider (PCP) factors associated with adherence to American Cancer Society (ACS) and United States Preventive Services Task Force (USPSTF) guidelines for average risk colorectal cancer (CRC) screening.MethodsRetrospective case-control study of medical and pharmacy claims from the Optum Research Database from 01/01/2014 − 12/31/2018. Enrollee sample was adults aged 50 − 75 years with ≥ 24 months continuous health plan enrollment. Provider sample was PCPs listed on the claims of average-risk patients in the enrollee sample. Enrollee-level screening opportunities were based on their exposure to the healthcare system during the baseline year. Screening adherence, calculated at the PCP level, was the percent of average-risk patients up to date with screening recommendations each year. Logistic regression modelling was used to examine the association between receipt of screening and enrollee and PCP characteristics. An ordinary least squares model was used to determine the association between screening adherence among the PCP’s panel of patients and patient characteristics.ResultsAmong patients with a PCP, adherence to ACS and USPSTF screening guidelines ranged from 69 to 80% depending on PCP specialty and type. The greatest enrollee-level predictors for CRC screening were having a primary/preventive care visit (OR = 4.47, p < 0.001) and a main PCP (OR = 2.69, p < 0.001).ConclusionsIncreased access to preventive/primary care visits could improve CRC screening rates; however, interventions not dependent on healthcare system contact, such as home-based screening, may circumvent the dependence on primary care visits to complete CRC screening.

Colorectal Cancer Diagnostic Methods: The Present and Future.

To meet the needs of the colorectal cancer (CRC) patient population, colorectal cancer screening is continuously updated. The most significant advice is to start CRC screening exams at age 45 for people at average risk for CRC. CRC testing is divided into two categories: stool-based tests and visual inspections. High-sensitivity guaiac-based fecal occult blood testing, fecal immunochemical testing, and multitarget stool DNA testing are stool-based assays. Colon capsule endoscopy and flexible sigmoidoscopy are visualization examinations. There have been arguments about the importance of these tests in detecting and managing precursor lesions because of the lack of validation of screening results. Recent advancements in artificial intelligence and genetics have prompted the creation of newer diagnostic tests, which require validation in diverse populations and cohorts. In this article, we have discussed the present and emerging diagnostic tests.

Adenoma Detection Rate in Average-Risk Population: An Observational Consecutive Retrospective Study.

Although colonoscopy is considered the most effective tool for reducing colorectal cancer-related morbidity, the age at which average-risk individuals begin colonoscopic screening is undetermined. This study aimed to compare the adenoma and advanced adenoma detection rates according to age and sex in a large average-risk population in the rural areas of Eastern China. This observational, single-center, retrospective study included patients with average colorectal cancer risk and examined the adenoma and advanced adenoma detection rates using age intervals of 5years. We also compared the size and age of patients with and without advanced adenoma. We included 18928 patients with a median age of 54 years (range 15-90years), including 10143 men and 8785 women. The adenoma and advanced adenoma detection rates were 17.08% and 5.24%, respectively, and increased with age in the whole population. The adenoma detection rates increased from 8.97% (aged 40-44) to 14.98% (aged 45-49) and 6.24% (aged 45-49) to 11.00% (aged 50-54) in men and women (both P < .001), respectively. The advanced adenoma detection rates increased from 2.19% (aged 40-44) to 4.76% (aged 45-49) and 1.89% (aged 45-49) to 3.13% (aged 50-54) in men (P = .002) and women (P = .056), respectively. Patients with advanced adenomas were significantly older than those with non-advanced adenomas (P < .001). The tumors in the advanced adenoma group were significantly larger than those in the non-advanced adenoma group (P < .001). The adenoma and advanced adenoma detection rates increased significantly in average-risk population aged 45years and older, especially in men.