Colorectal Cancer Screening Strategies Research Articles

High-Throughput Metabolic Pattern Screening Strategy for Early Colorectal and Gastric Cancers Based on Covalent Organic Frameworks-Assisted Laser Desorption/Ionization Mass Spectrometry.

Precise early diagnosis and staging are conducive to improving the prognosis of colorectal cancer (CRC) and gastric cancer (GC) patients. However, due to intrusive inspections and limited sensitivity, the prevailing diagnostic methods impede precisely large-scale screening. In this work, we reported a high-throughput serum metabolic patterns (SMP) screening strategy based on covalent organic frameworks-assisted laser desorption/ionization mass spectrometry (hf-COFsLDI-MS) for early diagnosis and staging of CRC and GC. Notably, 473 high-quality SMP were extracted without any tedious sample pretreatment and coupled with multiple machine learning algorithms; the area under the curve (AUC) value is 0.938 with 96.9% sensitivity for early CRC diagnosis, and the AUC value is 0.974 with 100% sensitivity for early GC diagnosis. Besides, the discrimination of CRC and GC is accomplished with an AUC value of 0.966 for the validation set. Also, the screened-out features were identified by MS/MS experiments, and 8 metabolites were identified as the biomarkers for CRC and GC. Finally, the corresponding disordered metabolic pathways were revealed, and the staging of CRC and GC was completed. This work provides an alternative high-throughput screening strategy for CRC and GC and highlights the potential of metabolic molecular diagnosis in clinical applications.

The association between organised colorectal cancer screening strategies and reduction of its related mortality: a systematic review and meta-analysis

BackgroundTo assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality.MethodsWe systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results.ResultsWe summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years.ConclusionsA CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.

Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With a Blood Test That Meets the Centers for Medicare & Medicaid Services Coverage Decision.

A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for 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.

Causes of death in patients operated for colorectal cancer

BackgroundColorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants. MethodsAn Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution. Data on the underlying cause of death was extracted from the Registry of Vital Records and Statistics in Massachusetts. ResultsA total of 576 deaths were recorded in the database, of which 290 (50.35%) patients died of colorectal cancer. Deaths from colorectal cancer gradually decreased over time, whereas deaths from other cancers increased, and deaths from cardiovascular diseases remained stable. Patients who died from colorectal cancer were younger, died earlier in the disease course, had fewer comorbidities, higher rates of stage IV disease, rectal cancer, neoadjuvant therapy, extramural vascular invasion, perineural invasion, R0 resection, and preserved mismatch repair protein status. On multivariate analysis, age (adjusted odds ratio for 10-year increase = 0.79, 95% confidence interval 0.65–0.95), American Society of Anesthesiologists score (adjusted odds ratio = 0.64, confidence interval 0.42–0.98), stage IV disease (adjusted odds ratio = 3.02, confidence interval 1.59–5.9), neoadjuvant therapy (adjusted odds ratio = 7.91, confidence interval 2.64–28.13), extramural vascular invasion (adjusted odds ratio = 2.3, confidence interval 1.36–3.91) & time from diagnosis to death (adjusted odds ratio = 0.76, confidence interval 0.68–0.83) predicted death due to colorectal cancer versus other causes, whereas tumor location, perineural invasion, R0 resection, and mismatch repair protein status did not. ConclusionThere is a declining trend of deaths from colorectal cancer, presumably reflecting advances in colorectal cancer management strategies and better screening over time. However, younger patients disproportionately contribute to death due to colorectal cancer and need aggressive screening and management strategies.

Impact of revising colorectal cancer screening guidelines on health care resources in Canada.

78 Background: The rising incidence of early-onset colorectal cancer (CRC) has prompted U.S. organizations to lower the recommended CRC screening age for average risk adults from 50 to 45 years old, while Canadian programs remain unchanged. Canadian guidelines also differ from the U.S. in preferentially screening with a fecal immunochemical test (FIT) and recommending against colonoscopies as a screening test. Differences in national healthcare administration warrants investigation into the resource impact of updating screening guidance in Canada. Methods: Microsimulation modeling was performed using OncoSim (version 3.6) to project health and economic outcomes of different CRC screening strategies based on Canadian population data. Four simulated birth cohorts of the Canadian population born between 1973–1992 were tracked for a 40-year span from the year the oldest in each cohort turned 40 until the youngest in the same cohort turned 75. Colorectal adenoma rates were adjusted according to cohort risk ratios estimated from historical incidence data to reflect real-world CRC rates. Outcomes were reported for the cumulative cohort. Results: Compared to FIT screening at age 50, FIT screening at 45 reduced deaths by 5,220, incidence by 11,980, and added 96,100 health-adjusted life years (HALY). Colonoscopy screening at age 45 led to 17,870 fewer deaths, 74,250 fewer cases and added 314,960 HALYs. FIT and colonoscopy screening at age 45 had incremental costs of CAD$3,259 and $7,881 per HALY gained vs. a FIT at age 50, respectively. Across screening strategies, the greatest benefits were observed in the youngest cohort. Colonoscopy screening at age 45 resulted in 10,679,540 more total colonoscopies than the current capacity of 8,966,979 with FIT screening at age 50. Lowering the screening age to 45 with a FIT increased colonoscopy demand by 329,555. The total cost of CRC care (screening, diagnosis and treatment) increased with lower screening ages and colonoscopy first modalities, while the cost of CRC management (diagnosis and treatment) decreased with lower screening ages and colonoscopy first approaches. Conclusions: Adjusting current CRC screening guidelines demonstrates significant resource implications with proportional health benefits. Lower screening ages and colonoscopy first approaches have the largest resource demand and greatest health outcomes, while the incremental cost per HALY gained for all screening strategies is modest compared to standard benchmarks. [Table: see text]

Cost-Utility Analysis for Colorectal Cancer Screening According to the Initiating Age of National Cancer Screening Program in Korea.

This study aimed to identify the most cost-effective strategy for colorectal cancer screening using the fecal immunochemical test (FIT), focusing on screening initiation age in Korea. We designed Markov simulation models targeting individuals aged 40 years or older. Twelve strategies combining screening initiation ages (40, 45, or 50 years old), termination ages (80 or no limit), and intervals (1 or 2 years) were modeled, and the most cost-effective strategy was selected. The robustness of the results was confirmed using one-way and probabilistic sensitivity analyses. Furthermore, the cost-effectiveness of the qualitative and quantitative FIT methods was verified using scenario analysis. The 2-year interval strategy with a screening age range of 45-80 years was the most cost-effective (incremental cost-utility ratio = KRW 7,281,646/quality adjusted life years). The most sensitive variables in the results were transition rate from advanced adenoma to local cancer and discount rate. The uncertainty in the model was substantially low. Moreover, strategies starting at the age of 40 years were also cost-effective but considered suboptimal. The scenario analysis showed that there was no significant difference in cost-effectiveness between strategies with various relative screening ratio of quantitative and qualitative method. The screening method for advancing the initiation age, as presented in the 2015 revised national screening recommendations, was superior regarding cost-effectiveness. This study provides a new paradigm for the development of a national cancer screening system in Korea, which can be utilized as a scientific basis for economic evaluations.

Value of fecal immunochemical test in colorectal cancer screening

Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.

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.

Utilization of access to colorectal cancer screening modalities in low-income populations after medicaid expansion.

Colorectal cancer (CRC) remains a relevant public health problem. Current research suggests that racial, economic and geographic disparities impact access. Despite the expansion of Medicaid eligibility as a key component of the Affordable Care Act (ACA), there is a dearth of information on the utilization of newly gained access to CRC screening by low-income individuals. This study investigates the impact of the ACA's Medicaid expansion on utilization of the various CRC screening modalities by low-income participants. Our working hypothesis is that Medicaid expansion will increase access and utilization of CRC screening by low-income participants. To investigate the impact of the Affordable Care Act and in particular the effect of Medicaid expansion on access and utilization of CRC screening modalities by Medicaid state expansion status across the United States. This was a quasi-experimental study design using data from the Behavioral Risk Factor Surveillance System, a large health system survey for participants across the United States and with over 2.8 million responses. The period of the study was from 2011 to 2016 which was dichotomized as pre-ACA Medicaid expansion (2011-2013) and post-ACA Medicaid expansion (2014-2016). The change in utilization of access to CRC screening strategies between the expansion periods were analyzed as the dependent variables. Secondary analyses included stratification of the access by ethnicity/race, income, and education status. A greater increase in utilization of access to CRC screening was observed in Medicaid expansion states than in non-expansion states [+2.9%; 95% confidence interval (95%CI): 2.12, 3.69]. Low-income participants showed a +4.02% (95%CI: 2.96, 5.07) change between the expansion periods compared with higher income groups +3.19% (1.70, 4.67). Non-Hispanic Whites and Hispanics [+3.01% (95%CI: 2.16, 3.85) vs +5.51% (95%CI: 2.81, 8.20)] showed a statistically significant increase in utilization of access but not in Non-Hispanic Blacks, or Multiracial. There was an increase in utilization across all educational levels. This was significant among those who reported having a high school graduate degree or more +4.26 % (95%CI: 3.16, 5.35) compared to some high school or less +1.59% (95%CI: -1.37, 4.55). Medicaid expansion under the Affordable Care Act led to an overall increase in self-reported use of CRC screening tests by adults aged 50-64 years in the United States. This finding was consistent across all low-income populations, but not all races or levels of education.

Robotic Colonoscopy and Beyond: Insights into Modern Lower Gastrointestinal Endoscopy.

Lower gastrointestinal endoscopy is considered the gold standard for the diagnosis and removal of colonic polyps. Delays in colonoscopy following a positive fecal immunochemical test increase the likelihood of advanced adenomas and colorectal cancer (CRC) occurrence. However, patients may refuse to undergo conventional colonoscopy (CC) due to fear of possible risks and pain or discomfort. In this regard, patients undergoing CC frequently require sedation to better tolerate the procedure, increasing the risk of deep sedation or other complications related to sedation. Accordingly, the use of CC as a first-line screening strategy for CRC is hampered by patients' reluctance due to its invasiveness and anxiety about possible discomfort. To overcome the limitations of CC and improve patients' compliance, several studies have investigated the use of robotic colonoscopy (RC) both in experimental models and in vivo. Self-propelling robotic colonoscopes have proven to be promising thanks to their peculiar dexterity and adaptability to the shape of the lower gastrointestinal tract, allowing a virtually painless examination of the colon. In some instances, when alternatives to CC and RC are required, barium enema (BE), computed tomographic colonography (CTC), and colon capsule endoscopy (CCE) may be options. However, BE and CTC are limited by the need for subsequent investigations whenever suspicious lesions are found. In this narrative review, we discussed the current clinical applications of RC, CTC, and CCE, as well as the advantages and disadvantages of different endoscopic procedures, with a particular focus on RC.

Personalised colorectal cancer screening strategies: Information needs of the target population

Prior faecal Hemoglobin (f-Hb) concentrations of a negative fecal immunochemical test (FIT) can be used for risk stratification in colorectal cancer (CRC) screening. Individuals with higher f-Hb concentrations may benefit from a shorter screening interval (1 year), whereas individuals with undetectable f-Hb concentrations could benefit from a longer screening interval (3 year). Individuals’ views on personalised CRC screening and information needed to make a well-informed decision is unknown. We conducted three semi-structured focus groups among individuals eligible for CRC screening (i.e. men and women aged 55 to 75) in the Netherlands. Thematic analysis was used to analyse participants’ information need on personalised CRC screening strategies. Fourteen individuals took part. The majority were positive about CRC screening and indicated that they would participate in personalised CRC screening. The rationale for a longer interval among those at lowest risk was, however, unclear for many. The preferred information on individual risk was variable: ranging from full information to only information on the personalised strategy without mentioning the risk. It was not possible to address everyone’s need with a single approach. Additional communications, e.g. public media campaigns, billboards, videos on social media, were also suggested as necessary. This study showed that preferences on receiving information on individual CRC risk varied substantially and no consensus was reached. Introducing a personalised screening programme will require careful communication, particularly around the rationale for the strategy, and a layered approach to deliver information.

Yield and cost of government-organized colorectal cancer screening in young high-risk population in Northeast China

Guidelines for colorectal cancer (CRC) screening recommend screening at age 40 for high-risk population in China. However, the yield and cost of CRC screening in younger population are lacking. This analysis aimed to evaluate the yield and cost of CRC screening in high-risk 40- to 54-year-olds. Individuals aged 40–54 years who were determined to have a high risk of CRC were recruited from December 2012 to December 2019. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the detection rate of colorectal lesions among the three age groups and further calculated number of colonoscopies needed to screen (NNS) to detect one advanced lesion and cost of each group. The detection rates of advanced colorectal neoplasm in men aged 45–49 years (OR = 2.00, 95% CI: 0.93–4.30) and 50–54 years (OR = 2.19, 95% CI: 1.04–4.62) were higher than that aged 40–44 years. The detection rates of colorectal adenoma in women aged 50–54 years was higher than that aged 40–44 years (OR = 1.64, 95% CI: 1.23–2.19). Among the male screening population, NNS and cost to detect one advanced lesion in participants aged 45–49 years were similar to that aged 50–54 years, saving approximately half endoscopic resources and financial expenses compared with screening that aged 40–44 years. From the perspective of screening results and costs, it might be beneficial to delay the starting age of screening by gender. This study may provide reference for optimizing CRC screening strategies.

Effect of sedated colonoscopy with different cost coverage on improving compliance with colorectal cancer screening in China.

Colorectal cancer is the third most common cancer worldwide. Colonoscopy is the gold standard for colorectal cancer screening. However, the colonoscopy participation rate in China is much lower than that in Europe and the United States. As only non-sedated colonoscopies are offered in colorectal cancer screening programs in China, the absence of sedation may contribute to this gap. To explore the effect of free and partially participant-paid sedated colonoscopy on improving colorectal screening participation, we conducted a cross-sectional study under the framework of the Cancer Screening Program in Urban China in Xuzhou from May 2017 to December 2020. The Quanshan district was set as the control group and provided free non-sedated colonoscopy, the Yunlong district was set as a partial cost coverage group and offered partially participant-paid sedated colonoscopy, and the Gulou district was set as the full cost coverage group and offered free sedation colonoscopies. Multivariate logistic regression was used for multivariate analysis of colonoscopy participation and colorectal lesion detection rates between the groups. From May 2017 to May 2020, 81,358 participants were recruited and completed questionnaire, 7,868 subjects who met high-risk conditions for CRC were invited to undergo colonoscopy. The colonoscopy participation rates in the control group, partially cost coverage, and full cost coverage groups were 17.33% (594/3,428), 25.66% (542/2,112), and 34.41% (801/2,328), respectively. Subjects in the partial and full cost coverage groups had 1.66-fold (95% CI: 1.48-1.86) and 2.49-fold (95% CI: 2.23-2.76) increased rates compared with those in the control group. The adjusted PARs for the partially and the full cost coverage group was 9.08 (95% CI: 6.88-11.28) and 18.97 (95% CI: 16.51-21.42), respectively. The detection rates of CAN in the control, partial-cost coverage, and full-cost coverage groups were 3.54% (21/594), 2.95% (16/542), and 5.12% (41/801), respectively. There were no significant differences in the detection rates between the group. However, sedated colonoscopy increases costs. Sedated colonoscopy increased colonoscopy participation rates in both the partial and full cost-covered groups. A partial cost coverage strategy may be a good way to increase colorectal cancer participation rates and quickly establish a colorectal cancer screening strategy in underfunded areas.

Methylated SDC2 testing in stool DNA for early screening of colorectal cancer in Shipai Town, Dongguan City

Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ2=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.

Abstract 995: Evaluation of plasma cytokines and chemokines as potential biomarkers for colorectal cancer detection

Abstract Despite evidence suggesting that current Colorectal Cancer (CRC) screening strategies reduce mortality rates, screening compliance is suboptimal; for this, our study aimed to evaluate the discriminatory potential of plasma cytokine and chemokine levels for CRC detection in plasma samples in a Hispanic subpopulation. Using a retrospective case-control study design, we evaluated plasma samples in 20 CRC cases and 20 age-gender matched controls from the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). BD CBA Human Th1/Th2/Th17 Cytokine and Human Chemokine kits were used to prepare plasma samples for flow cytometric analysis (Becton-Dickinson &amp; Co). Mann-Whitney-U test was used to detect differences between biomarkers and case-control groups. Measures of diagnostic accuracy were estimated for comparisons according to CRC disease stage. We compared multivariable models to determine the best CRC case-classifier. The median levels of six of the cytokines evaluated (IL-2, IL-4, IL-6, IL-10, TNF, and IL-17A) and one chemokine (CXCL10-/IP-10) significantly differed between cases and controls (P&amp;lt;0.05). ROC plots and logistic regression analysis showed that these seven biomarkers displayed good to excellent accuracy (AUC: 0.6-0.9). Multivariate analysis showed that the best-case classifying model included the seven statistically significant markers. Our findings suggest that discriminatory biomarker levels between CRC cases and controls observed show their great potential as targets in novel blood-based screening tests for CRC. The development of a non-invasive CRC screening test will provide an alternative to increasing adherence, early detection, survivorship, and a tool for a population-based prevention strategy approach. Citation Format: Elba V. Caraballo, Hilmaris Centeno-Girona, Yilda Macias, Madeline M. Mártir Ocasio, Marcia R. Cruz-Correa. Evaluation of plasma cytokines and chemokines as potential biomarkers for colorectal cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 995.

Abstract 6525: Colon cancer screening and treatment with engineered probiotics

Abstract Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate selective colonization of CRC tumors with the orally-delivered probiotic E. coli Nissle 1917 (EcN) in genetically-engineered and orthotopic murine models of CRC, and human CRC patients. We subsequently engineer EcN to produce screening and therapeutic molecules, resulting in non-invasive detection of precursor CRC lesions and reduction of tumor burden through local induction of robust anti-tumor immunity. Citation Format: Candice R. Gurbatri, Georgette Radford, Jongwon Im, Courtney Coker, Nicholas Arpaia, Susan L. Woods, Daniel L. Worthley, Tal Danino. Colon cancer screening and treatment with engineered probiotics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6525.

Optimization of screening strategies for colorectal cancer based on fecal DNA and occult blood testing.

Fecal DNA and occult blood testing have been gradually developed for colorectal cancer (CRC) screening. Comparison of different testing strategies for these methods in CRC screening is in urgent need. This study aims to examine the efficacy of different testing strategies including multi-target fecal DNA testing, qualitative and quantitative fecal immunoassay tests (FITs). Fecal samples were collected from patients diagnosed by colonoscopy. Tests using fecal DNA, quantitative FIT or qualitative FIT were performed on same fecal samples. Efficiency of different testing strategies within different populations was investigated. For high-risk populations (CRC and advanced adenoma), the positive rate of the three methods alone was 74.3-80%; the positive predictive values (PPVs) ranged from 37.3% to 77.8%, and the negative predictive values (NPVs) ranged from 86.3% to 92.2%. For combined testing strategies, the positive rate was 71.4-88.6%, PPVs ranged from 38.3% to 86.2%, and NPVs ranged from 89.6% to 92.9%. Parallel fecal multi-target DNA test and quantitative FIT appears to be superior when using a combined testing strategy. For the normal population, no significant difference was identified in efficacy between these methods when used alone and in combination. Single testing strategy among the three methods is more suitable for the general population screening, and the combined testing strategy is more suitable for high-risk populations screening. The use of different combination strategies may have superiority in CRC high-risk population screening, but cannot conclude significant differences which may be attributed to the small sample size, large samples controlled trials are needed.

Application of Polypyrrole-Based Electrochemical Biosensor for the Early Diagnosis of Colorectal Cancer

Although colorectal cancer (CRC) is easy to treat surgically and can be combined with postoperative chemotherapy, its five-year survival rate is still not optimistic. Therefore, developing sensitive, efficient, and compliant detection technology is essential to diagnose CRC at an early stage, providing more opportunities for effective treatment and intervention. Currently, the widely used clinical CRC detection methods include endoscopy, stool examination, imaging modalities, and tumor biomarker detection; among them, blood biomarkers, a noninvasive strategy for CRC screening, have shown significant potential for early diagnosis, prediction, prognosis, and staging of cancer. As shown by recent studies, electrochemical biosensors have attracted extensive attention for the detection of blood biomarkers because of their advantages of being cost-effective and having sound sensitivity, good versatility, high selectivity, and a fast response. Among these, nano-conductive polymer materials, especially the conductive polymer polypyrrole (PPy), have been broadly applied to improve sensing performance due to their excellent electrical properties and the flexibility of their surface properties, as well as their easy preparation and functionalization and good biocompatibility. This review mainly discusses the characteristics of PPy-based biosensors, their synthetic methods, and their application for the detection of CRC biomarkers. Finally, the opportunities and challenges related to the use of PPy-based sensors for diagnosing CRC are also discussed.

Clinical performance of a multimodal screening blood test for advanced adenomas and CRC in an average-risk cohort of 1,038 participants.

75 Background: The National Polyp Study and 2021 USPSTF CRC-update highlight that the detection and removal of precancerous advanced adenomas (AA) prevents colorectal cancer (CRC), decreases mortality, and leads to higher cost savings than early cancer detection. Performance of a multimodal blood-based test for the detection of CRC and AA that integrates sensitive and accurate detection of circulating gastrointestinal epithelial cells and somatic oncologic variants as well as SEER data of the impact of sex and age is described. Methods: The prospective study included average-risk, asymptomatic screening subjects from 18 geographically dispersed US colonoscopy centers with blood drawn before colonoscopy. Monte Carlo cross-validation (MCCV) methods were used to evaluate the robustness of test performance through 2000 iterations of independent training and validation using bootstrap resampling with stratification to balance patient histopathology, age, and gender. Results include point estimates, confidence intervals, and distributions of sensitivity and specificity to detect AA and CRC. Results: The study cohort (53.2% female; mean age 56.7 yrs.) consisted of 1,038 subjects (White 65.1%; Black 8.5%; Hispanic 24.8%; Asian 1.7%); of which 954 (92%) were asymptomatic, average-risk screening subjects without age enrichment (including 11 CRC and 93 AA) and 84 (8%) were enriched case-control (65 CRC and 19 AA) subjects. The algorithm derives a test score from 0 (low risk) to 100 (high risk) as a quantitative measure of AA and CRC risk. A pre-defined cut point of 47.2 yields a test specificity &gt; 90%, and 92.1% and 54.5% sensitivity for the detection of CRC and AA, respectively. Estimated sensitivities and selected Clopper-Pearson (Exact) 95% confidence intervals based on validation results from MCCV are presented. A split analysis shows for the 954 intended-use, asymptomatic, average-risk screening subjects, the sensitivity for CRC and AA are 100% and 55.9%. Conclusions: A multi-site, prospective, average-risk CRC screening study using a multimodal assay had high sensitivity and specificity for AA and CRC. The quantitative correlation of test scores with disease pathology indicates that the modes of the assay interrogate the primary underlying pathophysiology of disease. The results demonstrate the potential of this novel test to meet the clinically unmet need for a noninvasive strategy for CRC screening and prevention that detects CRC and AA. Clinical trial information: NCT05127096 . [Table: see text]