Colorectal Cancer Mortality Research Articles

Emphasis on awareness of early-onset colorectal cancer

The incidence and mortality rates of early-onset colorectal cancer (EOCRC) among people under 50 years old are showing an upward trend. Although traditional epidemiological studies have conducted relatively deep research and screened out environmental factors related to EOCRC, our understanding of the causes, mechanisms, and treatment of this disease is still far from sufficient. In this review, we clarify the current progress of EOCRC, with a particular focus on epidemiology, screening status, clinical symptoms, and prognosis. This provides new evidence for secondary prevention, including precision screening, and offers new ideas for improving the diagnosis and treatment of EOCRC.

Sex differences in health-related quality of life and psychological distress among colorectal cancer patients: a 2-year longitudinal study.

While sex differences in the incidence and mortality of colorectal cancer (CRC) are well documented, less is known about sex differences in patients' health-related quality of life (HRQoL) and psychological distress. To enhance patient-tailored care, we aimed to longitudinally examine sex differences in HRQoL and psychological distress among CRC patients from diagnosis up until 2-year follow-up. Newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 334) completed questions on HRQoL (EORTC QLQ-C30) and psychological distress (HADS) before initial treatment (baseline), 4 weeks after surgery, and at 1 and 2 years after diagnosis. Also, HRQoL and psychological distress were assessed in a sex- and age-matched reference population. When directly comparing female (N = 126, 38%) and male (N = 208, 62%) CRC patients, female patients reported significantly worse HRQoL, such as more insomnia at baseline, worse physical and role functioning 4 weeks after surgery, more diarrhea at 1 year, and more pain and constipation at 2-year follow-up. However, a comparison with the reference population revealed larger differences between patients and reference in males than in females. For example, at 1- and 2-year follow-up, male patients reported significantly worse cognitive and social functioning, more insomnia, and more anxiety compared with a reference population. Especially male CRC patients reported worse HRQoL and more psychological distress when compared with a reference population. Knowledge of sex-specific differences in HRQoL and psychological distress among CRC patients may help healthcare providers anticipate and appropriately address patients' unique healthcare needs.

Cost-Utility Analysis of Berberine Chemoprevention for Colorectal Cancer After Polypectomy.

Background Chemoprevention, such as berberine, has been developed as an alternative or complementary strategy to colonoscopy surveillance and has shown promise in reducing the morbidity and mortality of colorectal cancer. This study aims to evaluate the cost-effectiveness of berberine for postpolypectomy patients from the US third-party payer. Methods A Markov microsimulation model was developed to compare the cost and efficacy of berberine to no intervention, colonoscopy, and the combination of berberine and colonoscopy in postpolypectomy patients. Results After simulating 1 million patients, the study found that colonoscopy alone had a mean cost of $16,391 andmean quality-adjusted life-years (QALYs) of 16.03 per patient, whereas adding berberine slightly reduced the mean cost to $15,609 with a mean QALY of 16.05, making it a dominant strategy. Berberine therapy alone was less effective than colonoscopy alone, with a higher mean cost of $37,480 and a mean QALY of 15.32 per patient. However, berberine therapy was found to be a dominant strategy over no intervention. Conclusions Adding berberine to colonoscopy is the most cost-saving and effective approach for postpolypectomy patients. For patients who refuse or have limited access to colonoscopy, berberine alone is likely to be a dominant strategy compared to no intervention.

Association Between Vitamin B12 Intake and Mortality in Patients with Colorectal Cancer: The US National Health and Nutrition Examination Survey, 1999-2018

Vitamin B12 plays a role in DNA methylation, influencing the 1-carbon cycle; However, its effect on colorectal cancer (CRC) mortality remains uncertain. This study assessed the relationship between vitamin B12 intake and all-cause and cancer-specific mortality among CRC patients. We analyzed data from the NHANES from 1999 to 2018, using multivariable Cox regression, competing risk model, Kaplan-Meier survival curves, and stratified analysis with interaction effects. The studied involved 4,554 cancer patients (mean age 65.8 years, 47.6% males). Results from multivariate Cox regression indicated that each additional 1 mcg/day of dietary vitamin B12 independently increased the risk of all-cause (HR, 1.07; 95% CI: 1.04–1.09, p < 0.001) and cancer-specific mortality (HR, 1.04; 95% CI, 1.02-1.06; p < 0.001). Kaplan-Meier curves indicated a higher risk of all-cause mortality with increased vitamin B12 intake (Log rank p = 0.01). Subgroup analysis suggested that higher vitamin B12 intake correlated with increased all-cause mortality risk, especially in individuals with higher protein (HR, 1.04; 95% CI, 1.02-1.06; p = 0.019) or carbohydrate intake (HR, 1.03; 95% CI, 1.01-1.05; p = 0.04). Thus, higher vitamin B12 intake correlates with increased all-cause and cancer-specific mortality in CRC patients, particularly those with higher protein or carbohydrate intake.

Duration of risk reduction in colorectal cancer incidence and mortality after a complete colonoscopy in Ontario, Canada: a population-based cohort study

Colorectal cancer guidelines recommend screening colonoscopy every 10 years after a negative procedure. If risk reduction extends past 10 years, the recommended interval could be extended, reducing the burden on the individual and health-care system. We aimed to estimate the duration that patients remain at reduced risk of colorectal cancer incidence and mortality after a complete colonoscopy. We did a population-based cohort study of individuals aged 50-65 years between Jan 1, 1994, to Dec 31, 2017. We excluded individuals with previous exposure to colonoscopy or colorectal surgery, those previously diagnosed with colorectal cancer, or a history of hereditary or other bowel disorders. We followed up participants until Dec 31, 2018, and identified all colonoscopies performed in this time period. We used a 9-level time-varying measure of exposure, capturing time since last complete colonoscopy (no complete colonoscopy, ≤5 years, >5-10 years, >10-15 years, and >15 years) and whether an intervention was performed (biopsy or polypectomy). A Cox proportional hazards regression model adjusting for age, sex, comorbidity, residential income quintile, and immigration status was used to estimate the association between exposure to a complete colonoscopy and colorectal cancer incidence and mortality. 5 298 033 individuals (2 609 060 [49·2%] female and 2 688 973 [50·8%] male; no data on ethnicity were available) were included in the cohort, with a median follow-up of 12·56 years (IQR 6·26-20·13). 90 532 (1·7%) individuals were diagnosed with colorectal cancer and 44 088 (0·8%) died from colorectal cancer. Compared with those who did not have a colonoscopy, the risk of colorectal cancer in those who had a complete negative colonoscopy was reduced at all timepoints, including when the procedure occurred more than 15 years earlier (hazard ratio [HR] 0·62 [95% CI 0·51-0·77] for female individuals and 0·57 [0·46-0·70] for male individuals. A similar finding was observed for colorectal cancer mortality, with lower risk at all timepoints, including when the procedure occurred more than 15 years earlier (HR 0·64 [95% CI 0·49-0·83] for female participants and 0·65 [0·50-0·83] for male participants). Those who had a colonoscopy with intervention had a significantly lower colorectal cancer incidence than those who did not undergo colonoscopy if the procedure occurred within 10 years for females (HR 0·70 [95% CI 0·63-0·77]) and up to 15 years for males (0·62 [(0·53-0·72]). Compared with those who do not receive colonoscopy, individuals who have a negative colonoscopy result remain at lower risk for colorectal cancer incidence and mortality more than 15 years after the procedure. The current recommendation of repeat screening at 10 years in these individuals should be reassessed. Canadian Institutes of Health Research.

Association of county-level provider density and social vulnerability with colorectal cancer-related mortality

BackgroundHealth care providers play a crucial role in increasing overall awareness, screening, and treatment of cancer, leading to reduced cancer mortality. We sought to characterize the impact of provider density on colorectal cancer population-level mortality. MethodsCounty-level provider data, obtained from the Area Health Resource File between 2016 and 2018, were used to calculate provider density per county. These data were merged with county-level colorectal cancer mortality 2016–2020 data from the Centers for Disease Control and Prevention. Multivariable regression was performed to define the association between provider density and colorectal cancer mortality. ResultsAmong 2,863 counties included in the analytic cohort, 1,132 (39.5%) and 1,731 (60.5%) counties were categorized as urban and rural, respectively. The colorectal cancer-related crude mortality rate was higher in counties with low provider density versus counties with moderate or high provider density (low = 22.9, moderate = 21.6, high = 19.3 per 100,000 individuals; P < .001). On multivariable analysis, the odds of colorectal cancer mortality were lower in counties with moderate and high provider density versus counties with low provider density (moderate odds ratio 0.97, 95% confidence interval 0.94–0.99; high odds ratio 0.88, 95% confidence interval 0.86–0.91). High provider density remained associated with a lower likelihood of colorectal cancer mortality independent of social vulnerability index (low social vulnerability index and high provider density: odds ratio 0.85, 95% confidence interval 0.81–0.89; high social vulnerability index and high provider density: odds ratio 0.93, 95% confidence interval 0.89–0.98). ConclusionRegardless of social vulnerability index, high county-level provider density was associated with lower colorectal cancer-related mortality. Efforts to increase access to health care providers may improve health care equity, as well as long-term cancer outcomes.

Precision Colorectal Cancer Fecal Immunological Test Screening With Fecal-Hemoglobin-Concentration–Guided Interscreening Intervals

Given a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy. To demonstrate the applicability of personalized colorectal cancer (CRC) screening with f-Hb-guided screening intervals to reduce the number of FITs and colonoscopy with as equivalent efficacy as universal biennial screening. A retrospective cohort study for developing f-Hb-guided precision interscreening interval was conducted using data on a Taiwanese biennial nationwide FIT screening program that enrolled more than 3 million participants aged 50 to 74 years between 2004 and 2014. The cohort was followed up over time until 2019 to ascertain colorectal neoplasia and causes of death. A comparative study was further designed to compare the use of FIT and colonoscopy between the personalized f-Hb-guided group and the universal biennial screening group given the equivalent efficacy of reducing CRC-related outcomes. A spectrum of f-Hb-guided intervals was determined by using the Poisson regression model given the equivalent efficacy of a universal biennial screening. The use of FIT and colonoscopy for the pragmatic f-Hb-guided interval group was measured compared with the universal biennial screening group. Data analysis was performed from September 2022 to October 2023. Using data from the 3 500 250 participants (mean [SD] age, 57.8 [6.0] years) enrolled in the Taiwanese biennial nationwide FIT screening program, an incremental increase in baseline f-Hb associated with colorectal neoplasia and CRC mortality consistently was observed. Participants with different f-Hb levels were classified into distinct risk categories. Various screening intervals by different f-Hb levels were recommended. Using the proposed f-Hb-guided screening intervals, it was found that the personalized method was imputed to reduce the number of FIT tests and colonoscopies by 49% and 28%, respectively, compared with the universal biennial screening. The gradient relationship between f-Hb and colorectal neoplasia and CRC mortality was used to develop personalized FIT screening with f-Hb-guided screening intervals. Such a precision interscreening interval led to the reduced use of FIT test and colonoscopy without compromising the effectiveness of universal biennial screening.

Development and Implementation of a Digital Quality Measure of Emergency Cancer Diagnosis.

Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality. On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) in the Department of Veterans Affairs (VA) and Geisinger from 2016 to 2020. We validated measure accuracy and identified preceding MODs through standardized chart review of 100 records per cancer per health system. Using VA's longitudinal encounter and mortality data, we applied logistic regression to assess EP's association with 1-year mortality, adjusting for cancer stage and demographics. Among 38,565 and 2,914 patients with lung cancer and 14,674 and 1,649 patients with CRCs at VA and Geisinger, respectively, our dQM identified EPs in 20.9% and 9.4% of lung cancers, and 22.4% and 7.5% of CRCs. Chart reviews revealed high positive predictive values for EPs across sites and cancer types (72%-90%), and a substantial percent represented MODs (48.8%-84.9%). EP was associated with significantly higher odds of 1-year mortality for lung cancer and CRC (adjusted odds ratio, 1.78 and 1.83, respectively, 95% CI, 1.63 to 1.86 and 1.61 to 2.07). A dQM for cancer EP was strongly associated with both mortality and MODs. The findings suggest a promising automated approach to measuring quality of cancer diagnosis in US health systems.

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

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. 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. 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. 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.

Longer Interval Between First Colonoscopy With Negative Findings for Colorectal Cancer and Repeat Colonoscopy

For individuals without a family history of colorectal cancer (CRC), colonoscopy screening every 10 years is recommended to reduce CRC incidence and mortality. However, debate exists about whether and for how long this 10-year interval could be safely expanded. To assess how many years after a first colonoscopy with findings negative for CRC a second colonoscopy can be performed. This cohort study leveraged Swedish nationwide register-based data to examine CRC diagnoses and CRC-specific mortality among individuals without a family history of CRC. The exposed group included individuals who had a first colonoscopy with findings negative for CRC at age 45 to 69 years between 1990 and 2016. The control group included individuals matched by sex, birth year, and baseline age (ie, the age of their matched exposed individual when the exposed individual's first colonoscopy with findings negative for CRC was performed). Individuals in the control group either did not have a colonoscopy during the follow-up or underwent colonoscopy that resulted in a CRC diagnosis. Up to 18 controls were matched with each exposed individual. Individuals were followed up from 1990 to 2018, and data were analyzed from November 2022 to November 2023. A first colonoscopy with findings negative for CRC, defined as a first colonoscopy without a diagnosis of colorectal polyp, adenoma, carcinoma in situ, or CRC before or within 6 months after screening. The primary outcomes were CRC diagnosis and CRC-specific death. The 10-year standardized incidence ratio and standardized mortality ratio were calculated to compare risks of CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals. The sample included 110 074 individuals (65 147 females [59.2%]) in the exposed group and 1 981 332 (1 172 646 females [59.2%]) in the control group. The median (IQR) age for individuals in both groups was 59 (52-64) years. During up to 29 years of follow-up of individuals with a first colonoscopy with findings negative for CRC, 484 incident CRCs and 112 CRC-specific deaths occurred. After a first colonoscopy with findings negative for CRC, the risks of CRC and CRC-specific death in the exposed group were significantly lower than those in their matched controls for 15 years. At 15 years after a first colonoscopy with findings negative for CRC, the 10-year standardized incidence ratio was 0.72 (95% CI, 0.54-0.94) and the 10-year standardized mortality ratio was 0.55 (95% CI, 0.29-0.94). In other words, the 10-year cumulative risk of CRC in year 15 in the exposed group was 72% that of the 10-year cumulative risk of CRC in the control group. Extending the colonoscopy screening interval from 10 to 15 years in individuals with a first colonoscopy with findings negative for CRC could miss the early detection of only 2 CRC cases and the prevention of 1 CRC-specific death per 1000 individuals, while potentially avoiding 1000 colonoscopies. This cohort study found that for the population without a family history of CRC, the 10-year interval between colonoscopy screenings for individuals with a first colonoscopy with findings negative for CRC could potentially be extended to 15 years. A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.

Nationally Automated Colonoscopy Performance Feedback Increases Polyp Detection: The NED APRIQOT Randomized Controlled Trial

Background and AimsPost-colonoscopy colorectal cancer incidence and mortality rates are higher for endoscopists with low polyp detection rates. Using the UK’s National Endoscopy Database (NED), which automatically captures real-time data, we assessed if providing feedback of case-mix-adjusted Mean Number of Polyps (aMNP), as a key performance indicator, improved endoscopists’ performance. Feedback was delivered via a theory-informed evidence-based audit and feedback intervention. MethodsThis multicentre, prospective, NED Automated Performance Reports to Improve Quality Outcomes Trial (NED-APRIQOT) randomised NHS endoscopy centres to intervention or control. Intervention-arm endoscopists were emailed tailored monthly reports automatically generated within NED, informed by qualitative interviews and behaviour change theory. The primary outcome was endoscopists’ aMNP during the 9-month intervention. ResultsFrom November 2020-July 2021, 541 endoscopists across 36 centres (19 intervention; 17 control) performed 54,770 procedures during the intervention, and 15,960 procedures during the 3-months post-intervention period. Comparing intervention-arm to control-arm endoscopists during the intervention period: aMNP was non-significantly higher (7%, 95% confidence interval (CI) -1% to 14%; p=0·08). Unadjusted MNP (10%, 95%CI 1-20%) and polyp detection rate (PDR) (10%, 95%CI 4-16%) were significantly higher. Differences were not maintained in the post-intervention period. In the intervention-arm, endoscopists accessing NED-APRIQOT webpages had higher aMNP than those who did not (118 vs 102 aMNP, p=0.03). ConclusionAlthough our automated feedback intervention did not increase aMNP significantly in the intervention period; MNP and PDR did significantly improve. Engaged endoscopists benefited most and improvements were not maintained post-intervention; future work should address engagement in feedback and consider the effectiveness of continuous feedback.www.isrctn.org ISRCTN11126923

Post-diagnosis physical activity and sedentary behaviour and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose-response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%-60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.

Utilization of colorectal cancer screening tests across European countries: a cross-sectional analysis of the European health interview survey 2018–2020

Colorectal cancer (CRC) screening has been shown to reduce CRC incidence and mortality, and most European countries have started to implement CRC screening programs in the past 20 years. Consequently, this study aimed to estimate the utilization of fecal tests and colonoscopy, as well as investigate factors associated with their utilization based on specific screening program characteristics in European countries. We analyzed data from the European Health Interview Survey 2018-2020 to determine the utilization of fecal tests [guaiac-based fecal occult blood test (gFOBT) or fecal immunochemical test (FIT)] within the preceding 2 years or colonoscopy within the preceding 10 years among people aged 50-74 years, based on the type of screening offered in each country. Using multivariable logistic regression and sub-group meta-analysis, factors associated with screening use were determined. The analyses included data from 129,750 respondents across 29 European countries, with participant counts ranging from 1511 individuals in Iceland to 11,755 individuals in Germany. Unit response rates ranged from 22% to 88%. The use of either test was highest among countries with fully rolled-out programs with fecal tests [from 37.7% (867/2379) in Croatia to 74.9% (2321/3085) in Denmark] and in countries offering colonoscopy as an alternative screening method [from 26.2% (854/3329) in Greece to 75.4% (1192/1760) in Luxembourg]. We observed the lowest utilization of either test in countries with no program or small-scale programs [6.3% (195/3179) in Bulgaria to 34.2% (722/2144) in Latvia]. Across all types of screening offers, younger age, being without a partner, low education, rural residence, and living in large households were associated with lower utilization, as were poor lifestyle scores and prolonged periods without physician consultation. Our findings point to large disparities and much room for improvement in CRC screening offers and utilization across Europe. There was no funding source for this study.

Colorectal Cancer Screening After Sequential Outreach Components in a Demographically Diverse Cohort

Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.

Colorectal cancer screening: A review of current knowledge and progress in research.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally. Despite the progress in screening, early diagnosis, and treatment, approximately 20%-25% of CRC patients still present with metastatic disease at the time of their initial diagnosis. Furthermore, the burden of disease is still expected to increase, especially in individuals younger than 50 years old, among whom early-onset CRC incidence has been increasing. Screening and early detection are pivotal to improve CRC-related outcomes. It is well established that CRC screening not only reduces incidence, but also decreases deaths from CRC. Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality, though variations in efficacy have been reported across the literature. However, uncertainties persist regarding the optimal screening method, age intervals and periodicity. Moreover, adherence to CRC screening remains globally low. In recent years, emerging technologies, notably artificial intelligence, and non-invasive biomarkers, have been developed to overcome these barriers. However, controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice. In this review, we aim to cover the current evidence surrounding CRC screening. We will further critically assess novel approaches under investigation, in an effort to differentiate promising innovations from mere novelties.

Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment

The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD = 1.99, P = 1.76 × 10−8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P = 3.21 × 10−14; 543 patients) and 1.80 (P = 1.11 × 10−9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. Therefore, our findings demonstrate the integrated contribution of pathologic characteristics, germline variants, and lifestyle exposure to the prognosis of colorectal cancer patients.

Distance to endoscopy services amplifies racial inequities in colorectal cancer mortality in Washington state

BackgroundThis study evaluates relationships among race, access to endoscopy services, and colorectal cancer (CRC) mortality in Washington state (WA). MethodsWe overlayed the locations of ambulatory endoscopy services with place of residence at time of death, using Department of Health data (2011–2018). We compared CRC mortality data within and outside a 10 ​km buffer from services. We used linear regression to assess the impact of distance and race on age at death while adjusting for gender and education level. ResultsAge at death: median 72.9y vs. 68.2y for white vs. non-white (p ​< ​0.001). The adjusted model showed that non-whites residing outside the buffer died 6.9y younger on average (p ​< ​0.001). Non-whites residing inside the buffer died 5.2y younger on average (p ​< ​0.001), and whites residing outside the buffer died 1.6y younger (p ​< ​0.001). We used heatmaps to geolocate death density. ConclusionsResults suggest that geographic access to endoscopy services disproportionately impacts non-whites in Washington. These data help identify communities which may benefit from improved access to alternative colorectal cancer screening methods.

Cirrhosis and Portal Hypertension Worsen Bowel Preparation for Screening Colonoscopy.

Colonoscopy is a diagnostic and therapeutic procedure that reduces colorectal cancer incidence and mortality but requires adequate bowel cleansing for high-quality examination. Past studies have suggested cirrhosis as a risk factor for worse bowel preparation. We carried out a match-controlled retrospective study evaluating patients with and without cirrhosis who underwent outpatient screening colonoscopies to assess the effect of cirrhosis and portal hypertension complications on preparation quality and endoscopic measures. We also did a subgroup analysis excluding patients with obesity. We examined 1464 patients with cirrhosis and matched controls. Cirrhotic patients had lower mean Boston Bowel Preparation Scale (BBPS) scores and slower cecal intubation times. We found a single point increase in the Model for End-stage Liver Disease (MELD) score, as well as ascites, hepatic encephalopathy, and variceal hemorrhage were all associated with a longer cecal intubation time. Subgroup analysis excluding patients with obesity again found a significantly lower BBPS score and longer cecal intubation time while also finding a 24% drop in polyp detection. Patients with cirrhosis have worse BBPS scores and longer cecal intubation times. Nonobese cirrhotic patients additionally have a lower polyp detection rate. Portal hypertension complications were associated with worsened preparation quality and longer cecal intubation times. Each incremental increase in MELD score lengthened cecal intubation time. These findings support a more aggressive bowel preparation strategy for patients with cirrhosis, especially patients with severe disease or portal hypertension complications.

COVID-related disruptions to colorectal cancer screening, diagnosis, and treatment could increase cancer Burden in Australia and Canada: A modelling study.

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020-2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.

Single-cell analysis revealed a potential role of T-cell exhaustion in colorectal cancer with liver metastasis.

Liver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T-cell exhaustion on LM in CRC is unclear. Single-cell sequencing data derived from the Gene Expression Omnibus database. Data were normalized using the Seurat package and subsequently clustered and annotated into different cell clusters. The differentiation trajectories of epithelial cells and T cells were characterized based on pseudo-time analysis. Single-sample gene set enrichment analysis (ssGSEA) was used to calculate enrichment scores for different cell clusters and to identify enriched biological pathways. Finally, cell communication analysis was performed. Nine cell subpopulations were identified from CRC samples with LM. The proportion of T cells increased in LM. T cells can be subdivided into NK/T cells, regulatory T cells (Treg) and exhausted T cells (Tex). In LM, cell adhesion and proliferation activity of Tex were promoted. Epithelial cells can be categorized into six subpopulations. The transformation of primary CRC into LM involved two evolutionary branches of Tex cells. Epithelial cells two were at the beginning of the trajectory in CRC but at the end of the trajectory in CRC with LM. The receptor ligands CEACAM5 and ADGRE5-CD55 played critical roles in the interactions between Tex and Treg cell-epithelial cell, which may promote the epithelial-mesenchymal transition process in CRC. Tex cells are able to promote the process of LM in CRC, which in turn promotes tumour development. This provides a new perspective on the treatment and diagnosis of CRC.