Surveillance colonoscopy findings in asymptomatic participants over 75 years of age.

Background and Aim: Surveillance colonoscopy for colorectal cancer (CRC) is generally not recommended beyond 75 years of age. The study determined incidence and predictors of advanced adenoma and CRC in older individuals undergoing surveillance colonoscopy. Methods: This was a retrospective cohort study of asymptomatic older participants (≥75 years), enrolled in a South Australian CRC surveillance program who underwent colonoscopy (2015-2020). Clinical records were extracted for demographics, personal or family history of CRC, comorbidities, polypharmacy, and colonoscopy findings. The associations between clinical variables and advanced adenoma or CRC at surveillance were assessed with multivariable Poisson regression analysis. Results: Totally 698 surveillance colonoscopies were analyzed from 574 participants aged 75-91 years (55.6% male). The incidence of CRC was 1.6% (11/698), while 37.9% (260/698) of procedures had advanced adenoma detected. Previous CRC (incidence rate ratio [IRR] 5.9, 95% CI 1.5-22.5), age ≥85 years (IRR 5.8, 95% CI 1.6-20.1) and active smoking (IRR 4.9, 95% CI 1.0-24.4) were independently associated with CRC diagnosis, while advanced adenoma at immediately preceding colonoscopy (IRR 1.6, 95% CI 1.3-2.0) and polypharmacy (IRR 1.2, 95% CI 1.0-1.5) were associated with advanced adenoma at surveillance colonoscopy in asymptomatic older participants (≥75 years). Conclusion: Advanced neoplasia was found in more than one third of the surveillance procedures completed in this cohort. Continuation of surveillance beyond age 75 yeasrs may be considered in participants who have previous CRC or are active smokers (provided they are fit to undergo colonoscopy). In other cases, such as past advanced adenoma only, the need for ongoing surveillance should be considered alongside participant preference and health status.

Progress in the field of noninvasive diagnostics for colorectal cancer: a systematic review for the accuracy of blood-based biomarkers for detection of advanced pre-cancerous lesions.

BACKGROUND: Early detection of pre-cancerous adenomas through screening can reduce colorectal cancer (CRC) incidence. Fecal immunochemical tests are commonly used, but have limited sensitivity for pre-cancerous lesions. Blood-based screening may improve test sensitivity. This systematic review and meta-analysis was conducted to evaluate the accuracy of blood-based biomarkers for detection of advanced pre-cancerous lesions. RESEARCH DESIGN AND METHODS: We present the accuracy of blood-based biomarkers for the detection of advanced pre-cancerous lesions. EMBASE, Web of Science and PubMed databases were searched, with study populations limited to adults diagnosed with advanced pre-cancerous lesions at colonoscopy, who had a blood-based biomarker test analyzed with reports of sensitivity and specificity. RESULTS: 69 studies were identified, which assessed 133 unique biomarkers sets. The best performing test was a panel of 6 miRNAs, with a sensitivity of 95% and specificity of 90% for advanced pre-cancerous lesions. Only 6 biomarkers demonstrated sensitivity ≥ 50% and specificity ≥ 90% for the detection of advanced pre-cancerous lesions. CONCLUSION: Many different blood-based biomarkers have been assessed for detection of advanced pre-cancerous lesions, but few have progressed beyond the discovery stage. While some biomarkers have reported high sensitivity and specificity, larger prospective studies in unbiased intended-use screening populations are required for validation.

The Diagnostic Accuracy of a Fecal Immunochemical Test in Detecting Colorectal Cancer and Advanced Precancerous Colorectal Neoplasia in Patients with Iron Deficiency: A Protocol for Systematic Review and Meta-Analysis.

Background. Iron deficiency (ID) is a common micronutrient deficiency and the leading cause of anemia worldwide. ID can be caused by chronic occult blood loss from colorectal neoplasia including colorectal cancer (CRC) and advanced precancerous colorectal lesions. Current guidelines recommend colonoscopy in both men and postmenopausal women presenting with ID anemia (IDA). However, there is controversy on the investigation of patients presenting with a lower risk of CRC including younger women with ID and those with nonanemic ID (NAID). There is a need for a triaging tool to identify which ID patients may benefit from colonoscopy. The fecal immunochemical test (FIT) is sensitive for CRC screening in an asymptomatic population, but its role in ID patients is unclear. The aim of this study is to conduct a systematic review to determine the diagnostic accuracy of FIT for detecting CRC and advanced precancerous neoplasia in individuals presenting with ID with or without anemia. Methods and Analysis. This protocol conforms with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A comprehensive search of the MEDLINE, Embase, and Web of Science databases will be undertaken for studies published after 2010 which involve patients with ID, who completed a FIT in the 6 months prior to colonoscopy, with FIT sensitivity and specificity calculated against the reference standard colonoscopy. The search will be limited to studies conducted after 2010 to reduce variability in colonoscopy quality. Risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Accuracy Studies version 2. FIT sensitivity and specificity will be the primary measure of diagnostic accuracy, and data will be analysed using a random effects meta-analysis. Discussion. This review and meta-analysis will be the first to systematically explore the value of the FIT as a triaging tool for patients with ID. This trial is registered with CRD42022367162.

Low Incidence of Colorectal Advanced Neoplasia During Surveillance in Individuals with a Family History of Colorectal Cancer.

BACKGROUND: Family history of colorectal cancer (CRC) is used to stratify individuals into risk categories which determine timing of initial screening and ongoing CRC surveillance. Evidence for long-term CRC risk following a normal index colonoscopy in family history populations is limited. AIMS: To assess the incidence of advanced neoplasia and associated risk factors in a population undergoing surveillance colonoscopies due to family history of CRC. METHODS: Surveillance colonoscopy findings were examined in 425 individuals with a family history of CRC, a normal index colonoscopy and a minimum of 10 years of follow-up colonoscopies. Advanced neoplasia risk was determined for three CRC family history categories (near-average, medium and high-risk), accounting for demographics and time after the first colonoscopy. RESULTS: The median follow-up was 13.5 years (IQR 11.5-16.0), with an incidence of advanced neoplasia of 14.35% (61/425). The number of affected relatives and age of CRC diagnosis in the youngest relative did not predict the risk of advanced neoplasia (p > 0.05), with no significant differences in advanced neoplasia incidence between the family history categories (p = 0.16). Patients ≥ 60 years showed a fourfold (HR 4.14, 95% CI 1.33-12.89) higher advanced neoplasia risk during surveillance than those < 40 years at index colonoscopy. With each subsequent negative colonoscopy, the risk of advanced neoplasia at ongoing surveillance was reduced. CONCLUSIONS: The incidence of advanced neoplasia was low (14.35%), regardless of the family history risk category, with older age being the main risk for advanced neoplasia. Delaying onset of colonoscopy or lengthening surveillance intervals could be a more efficient use of resources in this population.

Multiple Negative Fecal Immunochemical Tests Reduce Risk of Advanced Neoplasia in a Colonoscopy Surveillance Program.

BACKGROUND & AIMS: In above-average-risk individuals undergoing colonoscopy-based surveillance for colorectal cancer (CRC), screening with fecal immunochemical tests (FIT) between colonoscopies might facilitate personalization of surveillance intervals. Because a negative FIT is associated with a reduced risk for CRC, we examined the relationship between number of rounds of negative FIT and risk for advanced neoplasia in individuals undergoing surveillance colonoscopy. METHODS: We conducted a retrospective cohort study on 4021 surveillance intervals in 3369 individuals (50-74 years), who had completed a 2-sample FIT between colonoscopies, from 1 to 4 rounds at 1-2 yearly intervals, each with a negative result (<20 µg hemoglobin/g feces). Incidence of advanced neoplasia (CRC or advanced adenoma) was determined at the follow-up colonoscopy. Competing-risk regression was used to assess the association between multiple negative FIT results and the risk of advanced neoplasia within 2 years. RESULTS: The incidence of advanced neoplasia in the cohort was 9.9% and decreased with increasing numbers of rounds of negative FIT results: 11.1% after 1 negative FIT to 5.7% after 4 negative FIT. The risk of advanced neoplasia was significantly lower in participants with 3 (subdistribution hazard ratio, 0.50; 95% confidence interval, 0.24-0.97) and 4 (subdistribution hazard ratio, 0.33; 95% confidence interval, 0.15-0.73) rounds of negative FIT compared with only 1 negative FIT. CONCLUSIONS: There was a low risk of advanced neoplasia after multiple rounds of negative FIT in above-average-risk people undergoing surveillance with no neoplasia or nonadvanced adenoma at prior colonoscopy. This supports the use of interval FIT to personalize surveillance by lengthening colonoscopy intervals following multiple negative FIT results.

Patient attitudes towards changes in colorectal cancer surveillance: An application of the Health Belief Model.

OBJECTIVE: This is to determine whether health beliefs regarding colorectal cancer (CRC) screening could predict discomfort with a change to CRC surveillance proposing regular faecal immunochemical tests (FIT) instead of colonoscopy. METHODS: Eight hundred individuals enrolled in a South Australian colonoscopy surveillance programme were invited to complete a survey on surveillance preferences. Responses were analysed using binary logistic regression predicting discomfort with a hypothetical FIT-based surveillance change. Predictor variables included constructs based on the Health Belief Model: perceived threat of CRC, perceived confidence to complete FIT and colonoscopy (self-efficacy), perceived benefits from current surveillance and perceived barriers to FIT and colonoscopy. RESULTS: A total of 408 participants (51%) returned the survey (complete data n = 303; mean age 62 years, 52% male). Most participants (72%) were uncomfortable with FIT-based surveillance reducing colonoscopy frequency. This attitude was predicted by a higher perceived threat of CRC (OR = 1.03 [95% CI 1.01-1.04]), higher colonoscopy self-efficacy (OR = 1.34 [95% CI 1.13-1.59]) and lower perceived barriers to colonoscopy (OR = 0.92 [95% CI 0.86-0.99]). CONCLUSIONS: Health beliefs regarding colonoscopy and perceived threat of CRC may be important to consider when changing CRC surveillance protocols. If guideline changes were introduced, these factors should be addressed to provide patients reassurance concerning the efficacy of the alternative protocol.

Accuracy of blood-based biomarkers for screening precancerous colorectal lesions: a protocol for systematic review and meta-analysis.

INTRODUCTION: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer mortality worldwide. Most CRCs develop through either the adenoma-to-carcinoma or the serrated pathways, and, therefore, detection and removal of these precursor lesions can prevent the development of cancer. Current screening programmes can aid in the detection of CRC and adenomas; however, participation rates are suboptimal. Blood-based biomarkers may help to address these low participation rates in screening programmes. Although blood-based biomarker tests show promise for cancer detection, limited attention has been placed on the sensitivity and specificity for detection of the precursor lesions. The aim of this research is to conduct a systematic review and meta-analysis to evaluate the accuracy of blood-based biomarker tests in detecting advanced precancerous lesions. METHODS AND ANALYSIS: This protocol was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) and results will be reported in line with the PRISMA guidelines. Literature searches will be conducted on PubMed, Embase and Web of Science. Two reviewers will conduct the searches, and independently screen them, according to title and abstract and then the full-text versions of those selected articles as well as the risk of bias via the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2) tool. The Grading of Recommendations Assessment, Development and Evaluation guidelines will be used to validate the certainty of evidence for recommendations based on the risk of bias findings. Meta-analysis will be conducted where appropriate on groups of studies with low heterogeneity. ETHICS AND DISSEMINATION: No patient data will be included in our review and, therefore, ethics approval is not required. It is anticipated that the review will identify the most promising candidate biomarkers for clinical translation in the screening of advanced precancerous lesions. The results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021285173.

Detection of hypermethylated BCAT1 and IKZF1 DNA in blood and tissues of colorectal, breast and prostate cancer patients.

BACKGROUND: Detection of circulating cell-free DNA (ccfDNA) methylated in BCAT1 and IKZF1 is sensitive for detection of colorectal cancer (CRC), but it is not known if these biomarkers are present in other common adenocarcinomas. OBJECTIVE: Compare methylation levels of BCAT1 and IKZF1 in tissue and plasma from breast, prostate, and colorectal cancer patients. METHODS: Blood was collected from 290 CRC, 32 breast and 101 prostate cancer patients, and 606 cancer-free controls. Tumor and matched normal tissues were collected at surgery: 26 breast, 9 prostate and 15 CRC. DNA methylation in BCAT1 and IKZF1 was measured in blood and tissues. RESULTS: Either biomarker was detected in blood from 175/290 (60.3%) of CRC patients. The detection rate was higher than that measured in controls (48/606 (8.1%), OR = 18.2, 95%CI: 11.1-29.0). The test positivity rates in breast and prostate cancer patients were 9.4% (3/32) and 6.9% (7/101), respectively, and not significantly different to that measured in gender-matched controls (8.0% (33/382) females (OR = 0.84, 95%CI: 0.23-3.1) and 7.6% (26/318) males (OR = 0.86, 95%CI: 0.65-2.1). In tumor and non-neoplastic tissues, 93.5% (14/15) of CRC tumors were methylated in BCAT1 and/or IKZF1 (p< 0.004). Only 11.5% (3/26) and 44.4% (4/9) (p= 0.083) of breast and prostate tumors were hypermethylated in these two genes. CONCLUSIONS: Detection of circulating DNA methylated in BCAT1 and IKZF1 is sensitive and specific for CRC but not breast or prostate cancer.

Faecal immunochemical test mitigates risk of delayed colonoscopy in people with elevated risk of colorectal neoplasia.

BACKGROUND AND AIM: Surveillance colonoscopies may be delayed because of pressure on resources, such as the COVID-19 pandemic. This study aimed to determine whether delayed surveillance colonoscopy increases the risk for advanced neoplasia and whether interval screening with faecal immunochemical tests (FITs) and other known risk factors can mitigate this risk. METHODS: A retrospective cohort study of individuals undergoing surveillance colonoscopy for personal or family history of colorectal neoplasia was being provided with FIT between colonoscopies. Colonoscopy ≥ 6 months after the guideline-recommended interval was considered "delayed." Individuals were stratified based on prime colonoscopy findings to nonneoplastic findings, non-advanced adenoma, and advanced adenoma. The relative risk (RR) for developing advanced neoplasia was determined using a robust multivariable modified Poisson regression. RESULTS: Of 2548 surveillance colonoscopies, 1457 (57.18%) were delayed. Prior advanced adenoma, older age (> 60 years) and nonparticipation in interval FIT were associated with increased risk for advanced neoplasia (P < 0.05). There was a trend to increased risk in those with prior advanced adenoma with an increasing colonoscopy delay (P trend = 0.01). In participants who did not complete interval FIT and having advanced adenoma in the prime colonoscopy, risk of advanced neoplasia was 2.48 times higher (RR = 2.48, 95% confidence interval: 1.20-5.13) in participants who had beyond 2 years of delayed colonoscopy compared with those with on-time colonoscopy. Colonoscopy delay did not increase the risk of advanced neoplasia in participants with negative interval FIT results. CONCLUSION: Surveillance colonoscopy can be safely extended beyond 6 months in elevated colorectal cancer risk patients who do not have prior advanced adenoma diagnosis, particularly if interval FIT is negative.

The impact of coronavirus disease 2019 on surveillance colonoscopies in South Australia.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) global pandemic has affected elective procedures, including colonoscopy, worldwide. Delayed colorectal cancer surveillance may increase cancer risk. This study aimed to determine the impact of COVID-19 on the proportion of surveillance colonoscopies booked and completed and the extent to which that surveillance was delayed. METHODS: This was a retrospective analysis of colonoscopy data during the 3 months (April-June 2020) when clinical services were most affected by COVID-19 in South Australia compared to the same period in 2019. Data on colonoscopies and responses to surveillance recall letters were reviewed to determine the numbers and proportions of colonoscopies that were delayed. RESULTS: During 2020, the total number of colonoscopies decreased by 51.1% (n = 569) compared to 2019 (n = 1164). In 2019, 45.5% (n = 530) of colonoscopies were completed for surveillance, but this proportion decreased to 32.0% (n = 182) during 2020, an overall decrease in the number of surveillance colonoscopies of 65.6%. Of surveillance colonoscopies that were due in 2020, 46.1% (134/291) were delayed >6 months, a significant increase compared to 2019 (19.3%; 59/306, P < 0.001). A decrease in response to surveillance recall letters was only observed in patients ≥75 years, with more nonresponders (51.6%) in 2020 compared to that observed in 2019 (25.6%, P = 0.03). CONCLUSIONS: Significant delays in surveillance colonoscopies occurred during the COVID-19 pandemic in South Australia. These effects are likely to be in areas more severely affected by the pandemic. Planning for post-COVID-19 colonoscopy capacity is required to avoid cancer progression due to delays in surveillance colonoscopies.