Population-level impact of the BMJ Rapid Recommendation for colorectal cancer screening: a microsimulation analysis.

OBJECTIVE: In 2019, a BMJ Rapid Recommendation advised against colorectal cancer (CRC) screening for adults with a predicted 15-year CRC risk below 3%. Using Switzerland as a case study, we estimated the population-level impact of this recommendation. DESIGN: We predicted the CRC risk of all respondents to the population-based Swiss Health Survey. We derived the distribution of risk-based screening start age, assuming predicted risk was calculated every 5 years between ages 25 and 70 and screening started when this risk exceeded 3%. Next, the MISCAN-Colon microsimulation model evaluated biennial faecal immunochemical test (FIT) screening with this risk-based start age. As a comparison, we simulated screening initiation based on age and sex. RESULTS: Starting screening only when predicted risk exceeded 3% meant 82% of women and 90% of men would not start screening before age 65 and 60, respectively. This would require 43%-57% fewer tests, result in 8%-16% fewer CRC deaths prevented and yield 19%-33% fewer lifeyears gained compared with screening from age 50. Screening women from age 65 and men from age 60 had a similar impact as screening only when predicted risk exceeded 3%. CONCLUSION: With the recommended risk prediction tool, the population impact of the BMJ Rapid Recommendation would be similar to screening initiation based on age and sex only. It would delay screening initiation by 10-15 years. Although halving the screening burdens, screening benefits would be reduced substantially compared with screening initiation at age 50. This suggests that the 3% risk threshold to start CRC screening might be too high.

Integrating artificial intelligence techniques for advancements in colorectal cancer management: navigating past and predicting future direction.

Artificial Intelligence (AI) in the last few years has emerged as a valuable tool in managing colorectal cancer, revolutionizing its management at different stages. In early detection and diagnosis, AI leverages its prowess in imaging analysis, scrutinizing CT scans, MRI, and colonoscopy views to identify polyps and tumors. This ability enables timely and accurate diagnoses, initiating treatment at earlier stages. AI has helped in personalized treatment planning because of its ability to integrate diverse patient data, including tumor characteristics, medical history, and genetic information. Integrating AI into clinical decision support systems guarantees evidence-based treatment strategy suggestions in multidisciplinary clinical settings, thus improving patient outcomes. This narrative review explores the multifaceted role of AI, spanning early detection of colorectal cancer, personalized treatment planning, polyp detection, lymph node evaluation, cancer staging, robotic colorectal surgery, and training of colorectal surgeons.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma.

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

Costs and Projected Effect of a Federally Qualified Health Center-Based Mailed Colorectal Cancer Screening Program in Texas.

Introduction: Mailed stool testing for colorectal cancer (CRC) may improve screening uptake and reduce the incidence and mortality of CRC, especially among patients at federally qualified health centers (FQHCs). To expand screening programs it is important to identify cost-effective approaches. Methods: We developed a decision-analytic model to estimate the cost, effects on screening and patient outcomes (CRCs detected, CRCs prevented, CRC deaths prevented), and cost-effectiveness of implementing a state-wide mailed stool testing program over 5 years among unscreened, age-eligible (aged 50-75 y) patients at FQHCs in Texas. We compared various outreach strategies and organizational structures (centralized, regional, or a hybrid). We used data from our existing regional mailed stool testing program and recent systematic reviews to set parameters for the model. Costs included start-up and ongoing activities and were estimated in 2022 US dollars from the perspective of a hypothetical third-party payer. Cost-effectiveness was assessed by using both incremental and average cost-effectiveness ratios. Results: Using either a statewide centralized or hybrid organizational configuration to mail stool tests to newly eligible FQHC patients and patients who have responded at least once since program inception is likely to result in the best use of resources over 5 years, enabling more than 110,000 additional screens, detecting an incremental 181 to 194 CRCs, preventing 91 to 98 CRCs, and averting 46 to 50 CRC deaths, at a cost of $10 million to $11 million compared with no program. Conclusions: A statewide mailed stool testing program for FQHC patients can be implemented at reasonable cost with considerable effects on CRC screening outcomes, especially when its structure maximizes program efficiency while maintaining effectiveness.

"Too young to have this kind of diagnosis": A qualitative exploration of younger adults' experiences of colorectal cancer diagnosis.

OBJECTIVE: Colorectal cancer (CRC) incidence is rising among adults under the age of 50 (early- or young-onset CRC). This population is more likely to have advanced-stage disease at diagnosis, suggesting their diagnostic pathway may be prolonged. To better understand factors influencing this pathway, this study explored patients' experiences of decision-making during a diagnosis of young-onset CRC. METHODS: Semi-structured interviews were conducted with 17 participants with young-onset CRC diagnosed in 2021-2022 in Victoria, Australia. Interviews were conducted online or by phone an average 7 months (range 1-13) after diagnosis. Analysis was approached from a critical realist perspective, with themes developed inductively using reflexive thematic analysis. RESULTS: Five themes were identified: Shifting Perception of Urgency, Multidimensional Perception of Role, Making the Most of Resources, Stage of Life, and COVID Adds Complexity. Participants' decision-making evolved over the diagnostic period. As participants perceived urgency to act, they took on a more active role in decision-making, utilising personal resources to access timely care. Their decisions were shaped by stage-of-life considerations, including employment and caring for a young family, with the COVID-19 pandemic adding "…a whole other layer of complexity" to the process. CONCLUSIONS: Younger adults with CRC make decisions in the context of unique considerations, adapting to reduce time to diagnosis, with decisions complicated by the COVID-19 pandemic. Greater support from health care providers/systems in the diagnostic period may improve timeliness of CRC diagnosis and outcomes in younger adults.

Cardiovascular Health and Colorectal Cancer Screening in Black Men: A Cross-Sectional Analysis.

African American/Black (henceforth Black) men face disproportionate risks of morbidity and mortality from both cardiovascular disease (CVD) and colorectal cancer (CRC). The American Heart Association's Life's Simple 7 (LS7) tool was designed to examine predictors of CVD with included behaviors also linked to CRC risk (i.e., smoking status, weight, diet, and physical activity). However, no studies have combined LS7 assessment alongside CRC screening history, which serves as a proxy for assessing CRC risk, in Black men. In this study, Black men aged 45-75 participating in annual community wellness events were screened for 6 of 7 LS7 measures (excluding diet, LS6) and self-reported CRC screening. Analyses conducted using R 4.0.5. revealed that Black men (N = 680), with an average age of 57.3 years (SD = 7.5), reported poor (39.7%), intermediate (34.6%), or ideal (25.7%) LS6 scores with higher scores corresponding to lower risk for CVD. However, for every 1-point increase in LS6 scores (0-6), there was a 26% lower odds of reported CRC screening (p = .001). In the fully adjusted model, men with 4+ ideal LS6 behaviors had a 60% lower odds of self-reported CRC screening compared to those with two ideal LS6 behaviors (p < .001). These findings underscore the need for culturally relevant interventions for Black men across all levels of cardiovascular health (CVH) to increase CRC screening uptake.

The double burden of severe mental illness and cancer: a population-based study on colorectal cancer care pathways from screening to end-of-life care.

AIMS: Cancer is one of the main causes of death in persons with severe mental illness (SMI). Although their cancer incidence is similar, or sometimes even potentially lower compared to the general population, their cancer mortality remains higher. The role of healthcare provision and care equity in this mortality is increasingly being addressed in research, but available studies are limited in their scope. In this context, our aim was to compare colorectal cancer (CRC) care pathways from screening to end-of-life care in patients with and without pre-existing SMI on a national scale. METHODS: This research leverages real-world data from the French national health claims database, covering the entire population, to assess cancer screening, diagnosis, treatment and post-treatment follow-up as well as quality of care (QOC) pathways among patients with incident CRC in 2015-2018, considering whether they had pre-existing SMI. We matched patients with SMI with three patients without - on age, sex, region of residence, year of cancer incidence and cancer type and location at presentation - as well as nationally established quality of CRC care indicators and regression models adjusting for relevant socio-economic, clinical and care provider-related covariates. RESULTS: Among patients with incident CRC, 1,532 individuals with pre-existing SMI were matched with individuals without SMI. After adjusting for covariates, both colon and rectal cancer patients with SMI were less likely to participate in the national CRC screening programme and to receive advanced diagnostic examinations (e.g., colonoscopies and several complementary diagnostic examinations). They also had lower odds of receiving combined treatments (e.g., neoadjuvant chemotherapy, radiotherapy and excision) and of having access to targeted therapy or capecitabine but higher odds for invasive care (e.g., stoma). Colon cancer patients with SMI were also more likely to have no treatment at all, and rectal cancer patients with SMI were less likely to receive post-treatment follow-up. Suboptimal QOC was observed for both groups of patients, but to a higher extent for patients with SMI, with statistically significant differences for indicators focusing on diagnosis and post-treatment follow-up. CONCLUSIONS: Our findings reveal discrepancies across the care continuum of CRC between individuals with and without SMI and provide initial avenues on where to focus future efforts to address them, notably at the entry and exit stages of cancer care pathways, while calling for further research on the mechanisms preventing equity of physical healthcare for individuals with SMI.

Detecting colorectal cancer using genetic and epigenetic biomarkers: screening and diagnosis.

Colorectal cancer (CRC) is one of the most frequent types of cancer, with high incidence rates and mortality globally. The extended timeframe for developing CRC allows for the potential screening and early identification of the disease. Furthermore, studies have shown that survival rates for patients with cancer are increased when diagnoses are made at earlier stages. Recent research suggests that the development of CRC, including its precancerous lesion, is influenced not only by genetic factors but also by epigenetic variables. Studies suggest epigenetics plays a significant role in cancer development, particularly CRC. While this approach is still in its early stages and faces challenges due to the variability of CRC, it shows promise as a potential method for understanding and addressing the disease. This review examined the current evidence supporting genetic and epigenetic biomarkers for screening and diagnosis. In addition, we also discussed the feasibility of translating these methodologies into clinical settings. Several markers show promising potential, including the methylation of vimentin (VIM), syndecan-2 (SDC2), and septin 9 (SEPT9). However, their application as screening and diagnostic tools, particularly for early-stage CRC, has not been fully optimized, and their effectiveness needs validation in large, multi-center patient populations. Extensive trials and further investigation are required to translate genetic and epigenetic biomarkers into practical clinical use. biomarkers, diagnostic biomarkers.

Interleukin-6-Positive Immune Cells as a Possible New Immunologic Marker Associated With the Colorectal Cancer Prognosis.

Chronic inflammation creates tumor microenvironment (TME) that facilitates colorectal cancer (CRC) cell proliferation, migration, metastasis, and tumor progression. Interleukin-6 (IL-6) is a proinflammatory cytokine with a pleiotropic effect on CRC development. We aimed to evaluate IL-6 expression in tumor cells and in immune cells in TME, to assess the serum level and IL6 -174 G/C genotype distribution and to correlate the results with selected morphologic and clinical parameters that may add useful information in understanding the mechanisms of human CRC progression. A total of 153 patients with CRC were recruited in the current study. We assessed the IL-6 serum concentration through the ELISA method, the expression of IL-6 in tumor and in immune cells by immunohistochemical and double immunofluorescence staining, the MSI status by immunоhistochemistry for 4 mismatch repair (MMR) proteins, and the genotype distributions for IL6 -174G/C (rs1800795) single-nucleotide polymorphism through PCR-RFLP method. Our results showed that serum IL-6 level were increased in CRC patients as compared with healthy controls (P<0.0001), and in patients with cancers with advanced histologic type (type IV). However, the higher concentration (above the median of 55.71 pg/mL) was with borderline association with longer survival of the patients after surgical therapy (P=0.055, Log rank test). We also found that IL-6+ immune cells prevailed in the invasive front (IF) of tumors compared with the tumor stroma (TS) (P<0.0001). More IL-6+ cells were recruited in the tumors with less advanced histologic type (I+II), with stronger inflammatory infiltrate in the IF, in early pTNM stages (I+II), without lymph node and distant metastases and the higher levels of IL-6+ cells, especially in the IF, were associated with longer survival (P=0.012). The results of our study suggest that although the serum levels of IL-6 are higher in CRC, the increased IL-6+ cells in tumor microenvironment, both in the invasive front and in tumor stroma, as well as the higher serum levels are associated with good prognostic variables and longer survival of the patients mainly in the early stages of CRC.

Exploration of the application potential of serum multi-biomarker model in colorectal cancer screening.

Analyzing blood lipid and bile acid profile changes in colorectal cancer (CRC) patients. Evaluating the integrated model's diagnostic significance for CRC. Ninety-one individuals with colorectal cancer (CRC group) and 120 healthy volunteers (HC group) were selected for comparison. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoproteins (Apo) A1, ApoA2, ApoB, ApoC2, and ApoC3 were measured using immunoturbidimetric and colorimetric methods. Additionally, LC-MS/MS was employed to detect fifteen bile acids in the serum, along with six tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, CA19-9, CA242, CA50, and CA72-4. Group comparisons utilized independent sample t-tests and Mann-Whitney U tests. A binary logistic regression algorithm was applied to fit the indicators and establish a screening model; the diagnostic accuracy of individual Indicators and the model was analyzed using receiver operating characteristic (ROC) curves. The CRC group showed significantly lower levels in eight serum lipid indicators and eleven bile acids compared to the HC group (P < 0.05). Conversely, serum levels of TG, CA19-9, and CEA were elevated (P < 0.05). Among the measured parameters, ApoA2 stands out for its strong correlation with the presence of CRC, showcasing exceptional screening efficacy with an area under the curve (AUC) of 0.957, a sensitivity of 85.71%, and a specificity of 93.33%. The screening model, integrating ApoA1, ApoA2, lithocholic acid (LCA), and CEA, attained an impressive AUC of 0.995, surpassing the diagnostic accuracy of individual lipids, bile acids, and tumor markers. CRC patients manifest noteworthy alterations in both blood lipids and bile acid profiles. A screening model incorporating ApoA1, ApoA2, LCA, and CEA provides valuable insights for detecting CRC.

Inappropriate Ordering of Multitarget Stool DNA Tests for Colon Cancer Screening.

BACKGROUND: CRC screening is recommended for adults aged 45-75. Mt-sDNA is indicated for asymptomatic individuals between the ages of 45 and 85, but not for those with rectal bleeding, iron deficiency anemia, adenomatous polyps, previous colonoscopy within 10 years, family history of CRC, positive results from CRC screening tests within the past 6 months, or age less than 45 and greater than 85. We aimed to determine the prevalence of mt-sDNA use when not indicated and factors associated with inappropriate testing. METHODS: 7,345 patients underwent mt-sDNA testing and were randomized using EMERSE. Charts for the first 500 patients were reviewed to determine whether mt-sDNA was ordered appropriately according to the USPSTF criteria. Seven patients were excluded due to having more than one inappropriate ordering for mt-sDNA. RESULTS: Of 500 patients, 22.2% had an inappropriately ordered mt-sDNA test. The most common reason for inappropriate ordering was having a previous colonoscopy done within the past 10 years. Rates of inappropriate testing significantly varied by race and the specialty of the ordering provider, with internal medicine providers ordering the most mt-sDNA tests. Rates of inappropriate testing did not significantly vary by sex or type of insurance. DISCUSSION: Our study suggests that providers may not be familiar with guidelines for the indicated use of mtsDNA, leading to inappropriate referrals and increased costs. Patients at increased CRC risk would benefit from a more sensitive procedure such as a colonoscopy. Future studies could understand the motivation to order testing outside approved indications through provider surveys and interviews.

The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma.

Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.

Estimated impact and value of blood-based colorectal cancer screening at varied adherence compared with stool-based screening.

OBJECTIVE: This analysis estimated the outcomes of triennial blood-based colorectal cancer (CRC) screening at various adherence, including perfect adherence, compared with triennial multi-target stool DNA (mt-sDNA) screening at the reported real-world adherence rate. METHODS: The validated CRC-AIM model simulated a US cohort of average-risk individuals receiving triennial screening with mt-sDNA or blood-based test from ages 45 to 75 years. Modeled specificity and sensitivity were based on reported data. Adherence was set at a real-world rate of 65.6% for mt-sDNA and at 65.6%, relative 10% incremental increases from 65.6%, or 100% for the blood-based test. Costs of mt-sDNA and the blood-based test were based on prices for clinically available tests ($508.87 and $895, respectively). Value-based pricing was estimated at a willingness-to-pay threshold of $100,000. RESULTS: Both tests resulted in life-years gained (LYG), reduced CRC cases, and reduced deaths versus no screening. With adherence for mt-sDNA set at 65.6% and for blood-based test set at 100%, mt-sDNA resulted in 30% more LYG, 52% more averted CRC cases, and 32% more averted CRC deaths. At reported sensitivity and specificity rates, mt-sDNA at 65.6% adherence dominates (is more effective and less costly) the blood-based test at any adherence. There was no price at which triennial screening with the blood-based test at any adherence was cost-effective compared with mt-sDNA at 65.6% adherence. CONCLUSIONS: Triennial screening with mt-sDNA resulted in better clinical outcomes at a lower cost compared with the modeled blood-based test even at perfect adherence, supporting application of blood-based tests only as a secondary screening option.

Blood-based colorectal cancer screening has lower diagnostic accuracy, lower clinical and health outcomes, and is more expensive than mt-sDNA, even with perfect blood-based screening participation. Although better than no screening at all, blood-based testing is unlikely to exceed performance of stool-based assessment unless a blood-based test is able to meaningfully detect precancerous growths.

Real-world data evaluating Guy's rapid diagnostic clinic as an alternate pathway for patients with FIT levels below 10.

OBJECTIVE: To analyse the effectiveness of rapid diagnostic clinics (RDCs) as an alternative pathway for patients with concerning symptoms and a faecal immunochemical test (FIT) result <10. Our primary endpoint was rate of colorectal cancer (CRC) detection. Second endpoints were rates of other cancers and gastrointestinal (GI) serious benign conditions. Finally, we analysed the specific pathway followed by FIT <10 patients with cancer at Guy's and St Thomas NHS Foundation Trust (GSTT) RDC. DESIGN: A retrospective and prospective cohort study. SETTING: GSTT RDC, one of England's largest single-centre RDCs. Sociodemographic and clinical characteristics of FIT <10 patients were analysed descriptively. PARTICIPANTS: Patients with an FIT result <10, seen at GSTT RDC between 1 January 2020 and 5 May 2023. RESULTS: A total of 1299 patients with an FIT<10 were seen at GSTT RDC between January 2020 and May 2023. Of these, 66% (n=861) reported weight loss, 62% (n=805) pain, 37% (n=481) fatigue, 34% (n=444) were anaemic and 23% (n=301) had nausea and vomiting. Among these patients, 7% (n=88) received a cancer diagnosis, 36% (n=462) were identified as having a serious benign condition. Within the patients with cancer, 9% (n=8) were diagnosed with CRC. Among patients with serious benign conditions, 7% (n=31) were referred to colorectal, hepatopancreatobiliary, or upper GI specialists. CONCLUSION: This study demonstrates the effectiveness of RDCs as an alternate pathway for FIT <10 patients with ongoing clinical concerns. These results contribute to enhancing patient care and optimising resource allocation within the healthcare system.