Reduce Colorectal Cancer Incidence Research Articles

Validation of Colorectal Cancer Models on Long-term Outcomes from a Randomized Controlled Trial.

Microsimulation models are often used to predict long-term outcomes and guide policy decisions regarding cancer screening. The United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial examines a one-time intervention of flexible sigmoidoscopy that was implemented before a colorectal cancer (CRC) screening program was established. Long-term study outcomes, now a full 17 y following randomization, have been published. We use the outcomes from this trial to validate 3 microsimulation models for CRC to long-term study outcomes. We find that 2 of 3 models accurately predict the relative effect of screening (the hazard ratios) on CRC-specific incidence 17 y after screening. We find that all 3 models yield predictions of the relative effect of screening on CRC incidence and mortality (i.e., the hazard ratios) that are reasonably close to the UKFSS results. Two of the 3 models accurately predict the relative reduction in CRC incidence 17 y after screening. One model accurately predicted the absolute incidence and mortality rates in the screened group. The models differ in their estimates related to adenoma detection at screening. Although high-quality screening results help to inform models, trials are expensive, last many years, and can be complicated by ethical issues and technological changes across the duration of the trial. Thus, well-calibrated and validated models are necessary to predict outcomes for which data are not available. The results from this validation demonstrate the utility of models in predicting long-term outcomes and in collaborative modeling to account for uncertainty.

Prospective evaluation on the impact of colonoscopy regarding the incidence of colorectal cancer

Objective: To evaluate the impact of colonoscopy on the incidence of colorectal cancer (CRC). Methods: This study was based on the Screening Project of Early Diagnosis and Treatment of CRC in Jiashan county, Zhejiang province. After excluding participants with incomplete information, these with individual history of CRC, those with CRC, enteritis or ulcer, noticed through colonoscopy exam at baseline, a total of 25 894 participants were finally included. Cox proportional hazards regression model was used to analyze the association between colonoscopy and the incidence of CRC. Results: This study was followed up for 160 113 person-years with a median of 5.67 years. During the follow-up period, 127 of them developed the CRC. The incidence rates of CRC in participants, were 202.35 per 100 000 person-years, 40.93 per 100 000 person-years and 63.62 per 100 000 person-years, respectively among the following three groups: who did not take the colonoscopy, without colorectal lesions or with benign colorectal lesions noticed by the colonoscopy and the differences were statistically significant (P<0.05). After adjusting for potential confounding factors, the HRs(95%CI) of CRC were 0.24 (0.16-0.36) and 0.29 (0.17-0.49), among those who did not have or had colorectal lesions in the participants who underwent the colonoscopy. Stratified by anatomic site, age and sex, results showed that the associations among the aforementioned groups were relatively stable. Conclusion: Colonoscopy could effectively contribute to the reduction of CRC incidence in the high-risk population.

S0280 Lowering the Colorectal Cancer Screening Age Improves Predicted Outcomes in Pre-Medicare and Medicare Populations in the CRC-AIM Microsimulation Model

INTRODUCTION: Most US guidelines recommend average risk colorectal cancer (CRC) screening for ages 50–75. An increasing CRC incidence among younger populations renders critical the need to evaluate the potential benefit of earlier CRC screening initiation. Using the validated CRC-AIM microsimulation model, we estimated the impact of lowering the CRC screening initiation age on outcomes for triennial multitarget stool DNA (mt-sDNA) or annual fecal immunochemical test (FIT) screening strategies. METHODS: Screening strategies were simulated for individuals free of diagnosed CRC at age 40 and screened from ages 50–75 or 45–75. CRC incidence, mortality, and life-years gained (LYG) were assessed for pre-Medicare eligible and Medicare eligible years (ages 65–75). Adherence rates were assumed to be as previously reported (71% for mt-sDNA vs 43% for FIT) or perfect (100%). Predicted outcomes of screening vs no screening are per 1000 individuals. Statistical differences between ages 45 and 50 were assessed by McNemar’s test. RESULTS: For individuals who initiated screening at age 45 with reported adherence, triennial mt-sDNA and annual FIT resulted in 23.9 and 24.4 more predicted LYG, respectively, versus starting screening at age 50 (Figure 1). With reported adherence, reductions in CRC incidence with mt-sDNA were 64.5% and 61.1% at screening start ages of 45 and 50, respectively, and with FIT were 53.7% and 49.9% (both P < 0.0001). Reductions in CRC mortality with mt-sDNA were 71.7% and 68.7% at screening start ages of 45 and 50, respectively, and with FIT were 62.7% and 59.0% (both P < 0.0001). Reductions in CRC cases and deaths were observed for both pre-Medicare and Medicare populations (Figures 2-3). With reported adherence, the number of CRC cases and deaths were lower with triennial mt-sDNA than annual FIT regardless of screening start age. Improvement in outcomes with earlier screening initiation were greater when assuming reported versus perfect adherence. CONCLUSION: Non-invasive stool-based screening tests may serve as effective early screening tools among younger populations. LYG and reductions in CRC incidence and mortality are greater when beginning screening at age 45 vs age 50, with gains applying to both pre-Medicare and Medicare populations. CRC outcomes were improved with a lower initiation age for both reported and perfect adherence model assumptions. When assuming reported adherence rates, mt-sDNA confers greater benefits than FIT.Figure 1.: Life-years gained (LYG) with triennial mt-sDNA and annual FIT assuming reported or perfect adherence and screening start ages of 45 or 50 years.Figure 2.: CRC cases per 1000 individuals with triennial mt-sDNA and annual FIT assuming reported or perfect adherence and screening start ages of 45 or 50 years. Results are shown for the pre-Medicare eligibility years (ages 45– or 50–64) or during Medicare eligibility (ages 65–75).Figure 3.: CRC deaths per 1000 individuals with triennial mt-sDNA and annual FIT assuming reported or perfect adherence and screening start ages of 45 or 50 years. Results are shown for the pre-Medicare eligibility years (ages 45– or 50–64) or during Medicare eligibility (ages 65–75).

S0279 Predicted Colorectal Cancer Outcomes With Reported Adherence to Follow-Up Colonoscopy After a Positive Stool-Based Test

INTRODUCTION: Colonoscopy (COL) non-adherence following a positive non-invasive colorectal cancer (CRC) screening test (e.g., multitarget stool DNA [mt-sDNA], fecal immunochemical test [FIT]) undermines the achievable benefits of screening. Given wide variations in the limited data reporting COL adherence after a positive non-invasive test, microsimulation modeling was used to estimate the clinical implications of this understudied input. METHODS: An average-risk US population cohort free of diagnosed CRC at age 40 that underwent triennial mt-sDNA or annual FIT screening from ages 50 to 75 was simulated using the validated CRC-AIM model. Three scenarios were modeled: (S1) assumed 100% adherence for initial screening and COL follow-up; (S2) reported adherence rates for initial mt-sDNA (71%) or FIT (43%) screening, with assumed 100% adherence to COL follow-up; and (S3) reported adherence rates for initial mt-sDNA or FIT screening and reported adherence rates for COL follow-up after positive mt-sDNA (73%) or FIT (47%). Sensitivity analyses were performed using 100% and reported adherence rates for mt-sDNA and FIT screening, with COL follow-up adherence ranging from 40%-100%. Patients without a COL follow-up were assumed to be non-adherent until CRC symptom onset. Outcomes for each scenario are per 1000 individuals. RESULTS: S1, S2, and S3 each yielded life-years gained (LYG) and reductions in CRC incidence and CRC mortality with either mt-sDNA or FIT screening vs no CRC screening (Table 1). Estimated LYG for mt-sDNA and FIT were 297 and 316 for S1, 284 and 245 for S2, and 203 and 113 for S3, respectively. Reductions in CRC incidence for mt-sDNA and FIT were 64% and 68% for S1, 61% and 50% for S2, and 43% and 23% for S3, respectively; reductions in CRC mortality were 72% and 76% for S1, 69% and 59% for S2, and 49% and 27% for S3, respectively. With assumed 100% adherence to mt-sDNA or FIT screening, the LYG transition was at 45% (LYG = 128) and 40% (LYG = 119) adherence for COL follow-up, respectively (Figure 1). At reported adherence for stool-tests, the additional LYG for mt-sDNA vs FIT ranged from 12 to 188 as follow-up COL adherence increased from 40% to 100% (Figure 2). CONCLUSION: These modeling analyses demonstrate that the inclusion of more realistic estimates for mt-sDNA, FIT, and COL follow-up adherence has substantial impact on the predicted outcomes. Using reported adherence rates, rather than assuming 100% adherence, mt-sDNA yields greater CRC screening benefits vs FIT.Table 1.: Predicted life-years gained (LYG), colorectal cancer (CRC) incidence reduction, and CRC mortality reduction for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) in 3 different adherence scenarios per 1000 individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 yearsFigure 1.: Percent difference in predicted life-years gained (LYG) per 1000 individuals assuming 100% adherence for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) at assumed adherence rate intervals for follow-up colonoscopy (COL) in individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 years. White boxes indicate 10% positive difference with mt-sDNA versus FIT. Dark gray boxes indicate >10% negative difference with mt-sDNA versus FIT.Figure 2.: Percent difference in predicted life-years gained (LYG) per 1000 individuals by reported adherence rates for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) at assumed adherence rate intervals for follow-up colonoscopy (COL) in individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 years. White boxes indicate 10% positive difference with mt-sDNA versus FIT. Dark gray boxes indicate >10% negative difference with mt-sDNA versus FIT.

One negative colonoscopy associated with a significant reduction in colorectal cancer risk.

An observational study published in the Annals of Internal Medicine1 found significant reductions in both colorectal cancer (CRC) incidence and mortality associated with a single negative high-quality screening colonoscopy. The findings indicate an 84% reduction in incidence and a 90% reduction in mortality for up to 17.4 years. As a result, the study authors suggest that the currently recommended 10-year screening interval is safe and could safely be extended. Under current guidelines, average-risk individuals aged 50 years or older who have previously had negative colonoscopy results are recommended to undergo screening every 10 years. That recommendation is based on estimates for how long it takes for adenomas and carcinomas to develop. However, longterm data are lacking on optimum follow-up intervals. The study was conducted by researchers from the Maria Sklodowska-Curie National Research Institute for Oncology in Warsaw, Poland. They analyzed a screening registry of 165,887 people and assessed both long-term CRC risk and CRC death after a single negative low- or high-quality screening colonoscopy. Their findings show that although a single negative screening colonoscopy was associated with significantly reduced CRC incidence and mortality during the 17-year screening period, only a high-quality colonoscopy led to a profound and stable reduction. Among women, high quality was key for long-term efficacy in screening colonoscopy in the proximal colon. These findings are particularly important because previous studies have questioned the efficacy of colonoscopy in the proximal colon as well as screening sigmoidoscopy in women.

Variation in changes in the incidence of colorectal cancer by age and association with screening uptake: an observational study

ObjectivesIn developed countries, the incidence of colorectal cancer (CRC) has declined in the over 50 years age group but increased in younger people. We studied CRC incidence by age and the influence of screening uptake.DesignAge-standardised and sex-standardised incidences for CRC from 1997 to 2017 were obtained from the Scottish Cancer Registry (SCR). In addition, linkage between the Scottish Bowel Screening Database and the SCR allowed investigation of any association between screening participation and CRC incidence.SettingScotland and the Scottish Bowel Screening Programme, in which guaiac faecal occult blood test screening was piloted from March 2000 and fully rolled by December 2009.ParticipantsFrom the introduction of screening in 2000 through to 2017, 2 395 172 were invited to participate, of whom 1 487 999 participated at least once.Main outcome measuresIncidence of CRC.ResultsIn the screening age range (50–74 years), CRC incidence peaked at 156.5 cases per 100 000 in 2010 after full roll-out of screening across Scotland but fell to 123.9 per 100 000 in 2017. However, under 50 years, there was a rise from 5.3 cases per 100 000 in 2000 to 6.8 per 100 000 in 2017. When CRC incidence was examined in those who had been offered screening, incidence fell in the participant group more than in the non-participant group after roll-out of screening was complete. Analysis of cumulative incidence demonstrated that CRC incidence in the participant group remained consistently below that of the non-participant from around 7 years of follow-up.ConclusionsThe incidence of CRC in Scotland has declined in the over 50 years age group but increased in younger people. It is likely that population screening has contributed to the reduction in CRC incidence in the over 50 years age group.

Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study.

Background Colonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously examined intermediate-risk patients from hospital data and identified a higher-risk subgroup who benefited from surveillance and a lower-risk subgroup who may not require surveillance. This study explored whether these findings apply in individuals undergoing CRC screening. Methods This retrospective study used data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST), English CRC screening pilot (ECP), and US Kaiser Permanente CRC prevention program (KPCP). Screening participants (50 – 74 years) classified as intermediate-risk at baseline colonoscopy were included. CRC data were available through 2006 (KPCP) or 2014 (UKFSST, ECP). Lower- and higher-risk subgroups were defined using our previously identified baseline risk factors: higher-risk participants had incomplete colonoscopies, poor bowel preparation, adenomas ≥ 20 mm or with high-grade dysplasia, or proximal polyps. We compared CRC incidence in these subgroups and in the presence vs. absence of surveillance using Cox regression. Results Of 2291 intermediate-risk participants, 45 % were classified as higher risk. Median follow-up was 11.8 years. CRC incidence was higher in the higher-risk than lower-risk subgroup (hazard ratio [HR] 2.08, 95 % confidence interval [CI] 1.07 – 4.06). Surveillance reduced CRC incidence in higher-risk participants (HR 0.35, 95 %CI 0.14 – 0.86) but not statistically significantly so in lower-risk participants (HR 0.41, 95 %CI 0.12 – 1.38). Conclusion As previously demonstrated for hospital patients, screening participants classified as intermediate risk comprised two risk subgroups. Surveillance clearly benefited the higher-risk subgroup.

Abstract 1103: Aspirin reduces the incidence of metastasis in a preclinical study of Braf mutant colorectal cancer

Abstract Background. Aspirin is a well-studied chemopreventive agent for the prevention of conventional colorectal adenomas and cancer. Post hoc analyses of cardiovascular prevention trials demonstrate a long-term reduction in colorectal cancer incidence and mortality with aspirin treatment. Randomized controlled trials have shown a long-term benefit for reducing colorectal cancer incidence in patients with Lynch Syndrome, a form of hereditary colorectal cancer. These findings have led to the recommendation of aspirin as a chemopreventive for colorectal cancer by the U.S. Preventive Services Task Force and Cancer Council Australia. However, future research questions have noted a lack of knowledge of the differential benefits of aspirin in preventing sessile serrated lesions versus conventional adenomas and cancer. In our study, we hypothesized that aspirin will be an effective long-term treatment for the prevention of colorectal cancer resulting from sessile serrated lesions. We aimed to investigate this in a preclinical study utilizing a murine model of Braf mutant serrated neoplasia with a primary end-point investigating cancer incidence. Methods. BrafV637E/+/Villin-CreERT2/+ mice were injected with tamoxifen (i.p. 75mg/kg) at 2 weeks of age to activate the Braf mutation within the intestine, then commenced on an aspirin-supplemented (n=78) or control standard (n=83) diet at wean. Aspirin was supplemented into the diet and provided ad libitum, at a human equivalent dose of 80-120mg per day, until sacrifice at 14 months. The gastrointestinal tract was excised and evaluated for the presence of carcinoma. In addition, the peritoneal and thoracic cavities were inspected for metastatic disease. A gastrointestinal pathologist (CL) assessed all histology sections. Results. At sacrifice, 14 months post induction of mutant Braf, all mice developed murine serrated lesions reminiscent of human sessile serrated lesions. We observed a carcinoma incidence of 31% (26/83) of which 35% (9/26) had metastasized to the liver or peritoneal cavity. When mice were treated with an aspirin-supplemented diet there was no significant reduction in carcinoma incidence (22/78, 28%, P = 0.7315). However, there was a significant reduction in the incidence of metastasis (1/22, 5%, P = 0.0134). Mice in the control group had lesions of a significantly greater size when compared to aspirin treated mice (P=0.0032). Conclusions. Aspirin resulted in a 7-fold decrease in metastases. This study demonstrates that the benefit of aspirin in preventing Braf mutant serrated neoplasia occurs at the carcinoma-metastasis phase of colorectal carcinogenesis. This could have potential clinical benefit in reducing recurrence and mortality. Citation Format: Alexandra Kane, Cheng Liu, Lochlan Fennell, Diane McKeone, Jennifer Borowsky, Barbara Leggett, Vicki Whitehall. Aspirin reduces the incidence of metastasis in a preclinical study of Braf mutant colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1103.

Screening and Surveillance Colonoscopy and COVID-19: Avoiding More Casualties

Screening and Surveillance Colonoscopy and COVID-19: Avoiding More Casualties

Tu1167 FELLOW INVOLVEMENT IN SCREENING COLONOSCOPY DOES NOT IMPROVE QUALITY OF THE PROCEDURE WHEN ATTENDING ADR IS HIGH

Colonoscopy is the preferred method for colorectal cancer (CRC) screening with established benefit in reducing CRC incidence and mortality. Interval CRC is inversely proportional to the quality of the procedure. Given the importance of providing a quality colonoscopy, there is great interest in studying the effects of different procedural factors on the Adenoma and Polyp Detection Rates (ADR and PDR). Colonoscopy quality differs widely among providers and is affected by several factors. It remains unclear whether participation of gastroenterology fellows affects the quality of the procedure, and whether the skill level at different stages of training contributes to any change in quality of the colonoscopy. We aim to investigate whether GI fellows at different stages of training have different ADR and PDR compared to screening colonoscopies performed by attendings without fellows. We performed a retrospective review of a random sample of patients who underwent a screening colonoscopy at our institution between January 2017 and June 2019. Patients with personal or family history of colon polyps or cancer, and those undergoing a diagnostic colonoscopy were excluded. Descriptive statistics were reported as proportions or means. Categorical variables were compared using Chi-Square test of association with a 95% confidence interval. A total of 895 colonoscopies met the inclusion criteria and were included in the analysis. The mean age of the study patients was 59 years, 51.1% were females. GI fellows were involved in 40.5% of the procedures. The ADR and PDR in the fellow participation group were similar to those in the attending group (42% vs 44%, p= 0.59; 54% vs 51%, p= 0.58, respectively). No significant differences were noted in ADR or PDR when first year fellows were excluded or when third year fellows were compared to the attending group. The ADR and PDR increased numerically with advancement in fellowship without reaching statistical significance (ADR = 38%, 40%, 49 % for first, second, and third year fellows respectively). In our sample, fellow involvement did not impact the ADR or PDR. However, the overall ADR was 43% which is significantly higher than the minimum acceptable ADR of 30% for men and 20% for women. While attendings and fellows have been appropriately vigilant in their mucosal inspection, the high ADR in both groups left little room for improvement. While data regarding fellow involvement on colonoscopy outcomes remains controversial, one could characterize it as “quality-neutral” as it is associated with at least equal ADR. Therefore, colonoscopy performed by a supervised fellow should not be disregarded for delivering low-quality services for patients. In addition, attending’s expertise appears to inversely correlate with the added potential benefit of fellow involvement.

Abstract C120: Evidence-based strategies to enhance colorectal cancer screening in American Indian communities

Abstract Despite the proven effectiveness of colorectal cancer (CRC) screening, American Indians (AIs) have some of the lowest CRC screening rates. Nearly two-thirds of US adults are current with US Preventive Services Task Force guidelines for CRC screening. In contrast, based on Indian Health Service (IHS) Government Performance and Results Act (GPRA) data, AI screening rates range from a low of 28% in the Phoenix Area, to 30% in the Albuquerque Area and a high of only 51% in the Oklahoma Area. The AI CRC Screening Consortium was formed by the National Cancer Institute-Designated Cancer Centers at the Universities of Arizona, New Mexico, and Oklahoma to address the major regional CRC screening disparities. The Consortium’s overall objective is to increase CRC screening delivery and uptake in AIs aged 50 to 75 years at average risk for CRC through the implementation of cost-effective multilevel, multicomponent evidence-based interventions (EBIs) across AI populations (on and off tribal lands) in the tri-state region. As part of the planning phase of the project (Year 1), we completed mixed-methods environmental scans (focus group and interviews, and readiness to change surveys) among tribal members and multisector healthcare providers practicing at Indian Health Service (IHS, I), Tribal (T), and Urban Indian (U) (I/T/U) healthcare facilities across the three states. In all, we conducted seven focus groups, 71 interviews, and three surveys at nine I/T/U healthcare facilities. We organized the focus group and interview data according to The Guide to Community Preventive Services (The Community Guide) recommendations for strategies to increase: community demand, community access, and provider delivery of CRC screening. We will provide quotes and summaries underscoring the EBIs and strategies recommended by the multisector healthcare action teams for implementation at their healthcare facilities. We will also describe the establishment of the Consortium and challenges experienced in conducting research with multiple tribal and federal entities and regulatory authorities. The use of community-academic participatory approaches has facilitated bidirectional and mutually beneficial knowledge integration, collaborative inter-dependent partnerships, equity in data ownership, and capacity enhancement. The scope of this project presents an opportunity to reduce CRC incidence and mortality affecting thousands of AIs. Our collaborative work will create opportunities for future research addressing the spectrum of CRC prevention, detection, and treatment in AI populations across the US. Citation Format: Shiraz I Mishra, Mark P Doescher, Jennifer Hatcher, Kevin English, Dorothy Rhoades, Peter Lance, Shane Pankratz, Jessica Blanchard, Nicholas Edwardson, Michelle Hopkins, Andrew Sussman, Zsolt Nagykaldi, Cheyenne Jim. Evidence-based strategies to enhance colorectal cancer screening in American Indian communities [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C120.

Long-Term Colorectal Cancer Incidence and Mortality After a Single Negative Screening Colonoscopy.

Current guidelines recommend a 10-year interval between screening colonoscopies, but evidence is limited. To assess the long-term risk for colorectal cancer (CRC) and death from CRC after a high- and low-quality single negative screening colonoscopy. Observational study. Polish Colonoscopy Screening Program. Average-risk individuals aged 50 to 66 years who had a single negative colonoscopy (no neoplastic findings). Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) of CRC after high- and low-quality single negative screening colonoscopy. High-quality colonoscopy included a complete examination, with adequate bowel preparation, performed by endoscopists with an adenoma detection rate of 20% or greater. Among 165887 individuals followed for up to 17.4 years, CRC incidence (0.28 [95% CI, 0.25 to 0.30]) and mortality (0.19 [CI, 0.16 to 0.21]) were 72% and 81% lower, respectively, than in the general population. High-quality examination resulted in 2-fold lower CRC incidence (SIR, 0.16 [CI, 0.13 to 0.20]) and mortality (SMR, 0.10 [CI, 0.06 to 0.14]) than low-quality examination (SIR, 0.32 [CI, 0.29 to 0.35]; SMR, 0.22 [CI, 0.18 to 0.25]). In multivariable analysis, the hazard ratios for CRC incidence after high-quality versus low-quality colonoscopy were 0.55 (CI, 0.35 to 0.86) for 0 to 5 years, 0.54 (CI, 0.38 to 0.77) for 5.1 to 10 years, and 0.46 (CI, 0.25 to 0.86) for 10 to 17.4 years. Only after high-quality colonoscopy did the SIR and SMR for 10.1 to 17.4 years of follow-up not differ compared with earlier observation periods. The general population was used as the comparison group. A single negative screening colonoscopy was associated with reduced CRC incidence and mortality for up to 17.4 years. Only high-quality colonoscopy yielded profound and stable reductions in CRC incidence and mortality throughout the entire follow-up. Polish Ministry of Health.

Promoting colorectal cancer screening: a systematic review and meta-analysis of randomised controlled trials of interventions to increase uptake

ABSTRACT Colorectal cancer (CRC) represents a global public health concern. CRC screening is associated with significant reductions in CRC incidence and mortality, however, uptake is suboptimal. This systematic review and meta-analysis of randomised controlled trials explored the effectiveness of interventions designed to increase screening uptake, plus the impact of various moderators. Data from 102 studies including 1.94 million participants were analysed. Results showed significant benefit of all interventions combined (OR, 1.49, 95% CI: 1.43, 1.56, p < 0.001). The effects were similar in studies using objective versus self-reported uptake measures and lower in studies judged to be at high risk of bias. Moderator analyses indicated significant effects for aspects of behaviour (effects lower for studies on non-endoscopic procedures), and intervention (effects higher for studies conducted in community settings, in healthcare systems that are not free, and that use reminders, health-professional providers, paper materials supplemented with in-person or phone contact, but avoid remote contact). Interventions that included behaviour change techniques targeting social support (unspecified or practical), instructions or demonstration of the behaviour, and that added objects to the environment produced stronger effects. The way in which findings can inform interventions to improve CRC screening uptake is discussed.

Association between the 2018 WCRF/AICR and the Low-Risk Lifestyle Scores with Colorectal Cancer Risk in the Predimed Study.

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascular risk. The 2018 WCRF/AICR and LRL scores were calculated. Multivariable Cox proportional regression models were fitted to estimate the HRs (hazard ratios) and 95% confidence intervals (CIs) for incident CRC events. During a median interquartile range (IQR) follow-up of 6.0 (4.4–7.3) years, 97 CRC events were considered. A significant linear association was observed between each 1-point increment in the WCRF/AICR score (score range from 0 to 7) and CRC risk (HR (95% CI) = 0.79 (0.63–0.99)). Similarly, each 1-point increment in the LRL score (score range from 0 to 5) was associated with a 22% reduction in CRC risk (0.78 (0.64–0.96)). Adhering to emergent lifestyle scores might substantially reduce CRC incidence in elderly individuals. Further longitudinal studies, which take different lifestyle indexes into account, are warranted in the future.

The importance of colonoscopy bowel preparation for the detection of colorectal lesions and colorectal cancer prevention.

Background and study aims Colonoscopy for colorectal cancer (CRC) screening has reduced CRC incidence and mortality and improved prognosis. Optimal bowel preparation and high-quality endoscopic technique facilitate early CRC detection. This review provides a narrative on the clinical importance of bowel preparation for colonoscopy and highlights available bowel preparations. Methods A PubMed search was conducted through June 2019 to identify studies evaluating clinical outcomes, efficacy, safety, and tolerability associated with bowel preparation for CRC screening-related colonoscopy. Results Selecting the optimal bowel preparation regimen is based on considerations of efficacy, safety, and tolerability, in conjunction with individual patient characteristics and preferences. Available bowel preparations include high-volume (4 L) and low-volume (2 L and 1 L), polyethylene glycol (PEG) solutions, sodium sulfate, sodium picosulfate/magnesium oxide plus anhydrous citric acid, sodium phosphate tablets, and the over-the-counter preparations magnesium citrate and PEG-3350. These preparations may be administered as a single dose on the same day or evening before, or as two doses administered the same day or evening before/morning of colonoscopy. Ingesting at least half the bowel preparation on the day of colonoscopy (split-dosing) is associated with higher adequate bowel preparation quality versus evening-before dosing (odds ratio [OR], 2.5; 95 % confidence interval [CI], 1.9−3.4). Conclusions High-quality bowel preparation is integral for optimal CRC screening/surveillance by colonoscopy. Over the last 30 years, patients and providers have gained more options for bowel preparation, including low-volume agents with enhanced tolerability and cleansing quality that are equivalent to 4 L preparations. Split-dosing is preferred for achieving a high-quality preparation.

A New Comprehensive Colorectal Cancer Risk Prediction Model Incorporating Family History, Personal Characteristics, and Environmental Factors.

Reducing colorectal cancer incidence and mortality through early detection would improve efficacy if targeted. We developed a colorectal cancer risk prediction model incorporating personal, family, genetic, and environmental risk factors to enhance prevention. A familial risk profile (FRP) was calculated to summarize individuals' risk based on detailed cancer family history (FH), family structure, probabilities of mutation in major colorectal cancer susceptibility genes, and a polygenic component. We developed risk models, including individuals' FRP or binary colorectal cancer FH, and colorectal cancer risk factors collected at enrollment using population-based colorectal cancer cases (N = 4,445) and controls (N = 3,967) recruited by the Colon Cancer Family Registry Cohort (CCFRC). Model validation used CCFRC follow-up data for population-based (N = 12,052) and clinic-based (N = 5,584) relatives with no cancer history at recruitment to assess model calibration [expected/observed rate ratio (E/O)] and discrimination [area under the receiver-operating-characteristic curve (AUC)]. The E/O [95% confidence interval (CI)] for FRP models for population-based relatives were 1.04 (0.74-1.45) for men and 0.86 (0.64-1.20) for women, and for clinic-based relatives were 1.15 (0.87-1.58) for men and 1.04 (0.76-1.45) for women. The age-adjusted AUCs (95% CI) for FRP models for population-based relatives were 0.69 (0.60-0.78) for men and 0.70 (0.62-0.77) for women, and for clinic-based relatives were 0.77 (0.69-0.84) for men and 0.68 (0.60-0.76) for women. The incremental values of AUC for FRP over FH models for population-based relatives were 0.08 (0.01-0.15) for men and 0.10 (0.04-0.16) for women, and for clinic-based relatives were 0.11 (0.05-0.17) for men and 0.11 (0.06-0.17) for women. Both models calibrated well. The FRP-based model provided better risk stratification and risk discrimination than the FH-based model. Our findings suggest detailed FH may be useful for targeted risk-based screening and clinical management.

Contribution of Surveillance Colonoscopy to Colorectal Cancer Prevention

The contribution of surveillance colonoscopy, as opposed to that of initial colonoscopy examination, to prevention of colorectal cancer (CRC) is uncertain. We estimated the preventive effect of surveillance colonoscopy by applying the recently developed metric of adenoma dwell time avoided needed to prevent 1 CRC case (DTA). We followed subjects in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial who underwent colonoscopies following positive findings from sigmoidoscopies (colonoscopy cohort, n = 15,935) for CRC incidence for 10 years. The number and timing of adenomas removed during surveillance were measured in a subset (n = 3492) of patients and extrapolated to the entire cohort to estimate the total avoided adenoma dwell time. A previously determined DTA value of 612 dwell years was applied to estimate the number of CRC cases prevented by surveillance. Proportional reduction in CRC was computed as CP/(CO+CP), where CO and CP are observed and estimated prevented cases, respectively. In the colonoscopy cohort of the PLCO, 2882 subjects had advanced adenomas (AAs), 572 had 3 or more non-advanced adenomas (NAA3+), 4496 had 1-2 non-advanced adenomas (NAA1-2), and 7985 had no adenoma (NA). The mean number of subsequent colonoscopy examinations over 10 years were 1.80 for subjects with AAs, 1.63 for subjects with NAA3+, and 1.46 for subjects with NAA1-2. Average years of avoided adenoma dwell time per subject were 4.0 for subjects with AAs, 5.5 for subjects with NAA3+, and 2.4 for subjects with NAA1-2. There were 56 cases of CRC in subjects with AAs, 4 cases of CRC in subjects with NAA3+, and 33 cases of CRC in subjects with NAA1-2. Estimated proportional reductions in CRC incidence were 25.0% in subjects with AAs (95% CI, 16%-34%), 34.4% in subjects with NAA1-2 (95% CI, 25%-40%), and 30.4% overall (in subjects with AAs, NAA3+, or NAA1-2; 95% CI, 25%-40%). Absolute CRC incidence reductions were 7.1 per 10,000 PY in subjects with AAs and 4.1 per 10,000 PY in subjects with NAA1-2. Using the recently developed metric of DTA, we estimated that surveillance colonoscopy in the PLCO colonoscopy cohort during 10 years of follow up prevented 30% of CRC cases. Because the methodology for estimation is indirect, the true effect is uncertain.

CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context.

Current screening trials are showing reduction in colorectal cancer incidence and mortality. However, participation rates are often low, and blood-based tests could complement existing screening strategies. CD26 protein (sCD26) and its dipeptidyl peptidase IV (DPP4) enzymatic activity in circulation have been proposed as biomarkers for colorectal cancer and other diseases. However, changes in sCD26 and DPP4 levels show complex degrees of correlation, and their physiological or pathophysiological role is unclear. The aim of this study was to analyse if anti-CD26 autoantibodies are related to sCD26 and DPP4 and to determine their relevance in a context of colorectal cancer screening for complementing the value of sCD26 and DPP4 as biomarkers. These biomarkers were measured in a large prospective cohort (n = 497, except the anti-CD26 antibodies, evaluated in 125 samples) that included a subgroup of individuals that were positive for the faecal immunological occult blood test (FIT) (n = 86) and underwent a colonoscopy (n = 47). We confirmed for the first time higher DPP4 activity in men compared to women (Student's t test, p = 0.002), though this difference between sexes was not seen for serum sCD26 protein. These biomarkers correlated (R = 0.246, p = 0.003) only in women. Correlations were found between anti-CD26 isotypes but not with DPP4 activity or sCD26 concentration, except for a negative correlation only in men between anti-CD26 IgA isotype and sCD26 (R = −0.232, p = 0.044), and an almost significant negative correlation between anti-CD26 IgG and sCD26 limited to FIT-positive men. Interestingly, patients with advanced adenomas displayed the most elevated mean levels of anti-CD26 IgA, IgM, and particularly IgG (Mann-Whitney U test, p = 0.030) in comparison with the other FIT positives without adenomas, and these levels did not correlate with sCD26 or its DPP4 activity. Our preliminary results suggest that the combination of these measures using sex as confounder could perhaps be used as biomarkers for colorectal disease. It also suggests that events affecting the gut influence the levels of anti-CD26 antibodies, which show little or no effect in antigen clearance. These findings should be confirmed in a larger cohort of individuals with colonoscopy. The physiological origin of the sex differences observed should be further addressed.

A comprehensive in vivo and mathematic modeling-based kinetic characterization for aspirin-induced chemoprevention in colorectal cancer.

Accumulating evidence suggests that aspirin has anti-tumorigenic properties in colorectal cancer (CRC). Herein, we undertook a comprehensive and systematic series of in vivo animal experiments followed by 3D-mathematical modeling to determine the kinetics of aspirin's anti-cancer effects on CRC growth. In this study, CRC xenografts were generated using four CRC cell lines with and without PIK3CA mutations and microsatellite instability, and the animals were administered with various aspirin doses (0, 15, 50, and 100 mg/kg) for 2 weeks. Cell proliferation, apoptosis and protein expression were evaluated, followed by 3D-mathematical modeling analysis to estimate cellular division and death rates and their impact on aspirin-mediated changes on tumor growth. We observed that aspirin resulted in a dose-dependent decrease in the cell division rate, and a concomitant increase in the cell death rates in xenografts from all cell lines. Aspirin significantly inhibited cell proliferation as measured by Ki67 staining (P < 0.05-0.01). The negative effect of aspirin on the rate of tumor cell proliferation was more significant in xenograft tumors derived from PIK3CA mutant versus wild-type cells. A computational model of 3D-tumor growth suggests that the growth inhibitory effect of aspirin on the tumor growth kinetics is due to a reduction of tumor colony formation, and that this effect is sufficiently strong to be an important contributor to the reduction of CRC incidence in aspirin-treated patients. In conclusion, we provide a detailed kinetics of aspirin-mediated inhibition of tumor cell proliferation, which support the epidemiological data for the observed protective effect of aspirin in CRC patients.

Colonoscopic screening is associated with reduced Colorectal Cancer incidence and mortality: a systematic review and meta-analysis.

It is the great priority to detect colorectal cancer (CRC) as early as possible, finally to reduce the incidence and mortality of CRC. However, although colonoscopy is recommended in many consensuses, yet no one systematic review is conducted to figure out how colonoscopy could change the incidence and mortality. In our study, we conducted a comprehensive meta-analysis to evaluate the association between colonoscopy screening and the incidence or mortality of CRC. PubMed, EMBASE, and PMC database were systematically searched from their inception to June 2020. A total of 13 cohort and 16 case-control studies comprising 4,713,778 individuals were obtained in this review. Our results showed that colonoscopy was associated with a 52% RR reduction in incidence of CRC (RR: 0.48, 95% CI: 0.46-0.49) and 62% RR reduction in mortality of CRC (RR: 0.38, 95% CI: 0.36-0.40). Subgroup analysis of different interventions, study design, country, sample size, age or sex showed that the incidence and mortality reduction remained consistent, and colonoscopy screening had the same effect on people below and above 50. Our study indicated that colonoscopy could significantly reduce the incidence and mortality of CRC.