Evaluating New Non-invasive Screening Tests for Colorectal Cancer: An In-Depth International Perspective-Introduction to a Special Issue of Digestive Diseases and Sciences.

Colorectal cancer (CRC) is a global disease accounting for nearly one in 10 cancer cases and deaths which can be reduced through CRC screening. In 2023 the World Endoscopy Organization (WEO) set forth twelve newly stated principles whereby new non-invasive CRC screening tests could be efficiently evaluated by a rigorous phased comparative approach. The complexities of evaluating new and evolving CRC screening tests and the necessity for a "one size does not fit all" approach was stressed.

The Impact of Age on Preferences for Colorectal Cancer Surveillance Strategies: Are Fecal Immunochemical Tests FIT for Surveillance?

Introduction: Individuals with a known risk of colorectal cancer (CRC) are recommended regular surveillance colonoscopies. Alternative surveillance strategies incorporating fecal immunochemical tests (FIT) may improve colonoscopy resource utilization and be more appropriate for those with a lower risk of CRC, particularly younger adults. This study compared younger (< 50 years) and older (≥ 50 years) adults' preferences for different CRC surveillance strategies.

Assessing Patient Preferences and Response to Extended Colonoscopy Intervals in a Colorectal Cancer Surveillance Program.

Background: Individuals with an increased risk of colorectal cancer (CRC) are advised to have surveillance colonoscopies at guideline-recommended intervals to prevent cancer development. As more recent clinical guideline updates have extended colonoscopy intervals for those with lower risk findings, effective communication of these surveillance changes is essential for ensuring patient acceptance.

Aims: To evaluate patient preferences for surveillance colonoscopy frequency, and responses to an extended colonoscopy interval.

Annual Blood Tests Are an Acceptable form of Surveillance to Supplement Colonoscopies for Colorectal Cancer.

Background: Individuals at increased risk of colorectal cancer (CRC) are recommended surveillance colonoscopies as a preventative measure, but timely provision of colonoscopies remains a significant hurdle. Biomarker testing has emerged as a potential strategy to mitigate excessive colonoscopy use by prioritizing procedures for those most at risk of CRC. However, the acceptability of supplementing surveillance colonoscopies with regular blood tests is unknown.

Fecal Immunochemical Test Positivity Thresholds: An International Survey of Population-Based Screening Programs.

Background: The fecal immunochemical test for hemoglobin (FIT) is now a widely used non-invasive test in population-based organized screening programs for colorectal neoplasia. The positivity thresholds of tests currently in use are based on the fecal hemoglobin concentration (f-Hb), but the rationale for the adopted thresholds are not well documented. To understand current global usage of FIT in screening programs we conducted an international survey of the brands of FIT used, the f-Hb positivity threshold applied and the rationale for the choice.

A blood test measuring DNA methylation of BCAT1 and IKZF1 for detection of lung adenocarcinoma.

Background: Colorectal (CRC) and lung adenocarcinoma share many genetic and pathological similarities. A circulating tumor DNA (ctDNA) test for CRC may also be useful for detection of lung adenocarcinoma. This study determined if a methylated BCAT1/IKZF1 ctDNA test for CRC can be used for detection of lung adenocarcinoma.

Accuracy, Acceptability, and Application: Fecal Immunochemical Tests for Early Detection of Advanced Neoplasia in Colonoscopy-Based Surveillance.

Background: The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening, but limited data exist for its application in individuals at above-average risk for CRC who complete surveillance colonoscopies.

Aim: To assess the accuracy, acceptability, and effectiveness of FIT in the interval between surveillance colonoscopies, for predicting advanced neoplasia (advanced adenoma or CRC) at the next colonoscopy.

Methods: Individuals enrolled in an Australian surveillance program were included.

, and : methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas.

Introduction: Methylated circulating tumour DNA (ctDNA) blood tests for (COLVERA) and (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize and methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection.

Comparing a fecal immunochemical test and circulating tumor DNA blood test for colorectal cancer screening adherence.

Background And Aim: Colorectal cancer (CRC) screening programs are most effective at reducing disease incidence and mortality through sustained screening participation. A novel blood test modality is being explored for CRC screening, but it is unclear whether it will provide sustained screening participation. This study aimed to investigate whether a circulating tumor DNA (ctDNA) blood test improved CRC screening re-participation when compared with a fecal immunochemical test (FIT) and to define the predictors of sustained CRC screening in an Australian population.

Evaluating the Role of Methylated Circulating Tumor DNA in Combination With Pathological Prognostic Factors for Predicting Recurrence of Colorectal Cancer.

Background: Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor DNA (ctDNA) at diagnosis could be used to improve the prediction for disease recurrence.

Objectives: To assess the impact of detecting methylated ctDNA at diagnosis in combination with demographic, lifestyle, clinical factors and tumor pathology, to assess predictive value for recurrence.

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.

Health utility assessments in individuals undergoing diagnostic and surveillance colonoscopy: improved discrimination with a cancer-specific scale.

Purpose: To compare the sensitivity and discriminant validity of generic and cancer-specific measures for assessing health-related quality of life (HRQoL) for individuals undergoing diagnostic or surveillance colonoscopy for colorectal cancer.

Methods: HRQoL was assessed using EQ-5D-5L (generic), and EORTC QLQ-C30 (cancer-specific) scales, 14 days after (baseline) and one-year following colonoscopy (follow-up). Utility scores were calculated by mapping EORTC-QLQ-C30 onto QLU-C10D.

The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy.

Background & Aims: An increasing burden on health care resources has resulted in a backlog of individuals requiring colonoscopy, with delays in surveillance possibly detrimental for individuals at increased risk of colorectal cancer (CRC). This study investigated the use of a 2-sample fecal immunochemical test (FIT) to establish those most likely to have advanced neoplasia (AN) and in need of prioritized surveillance colonoscopy.

Methods: This was a prospective study conducted in the tertiary care setting.

FIT for purpose: study protocol for a randomized controlled trial to personalize surveillance colonoscopy for individuals at elevated risk of colorectal cancer.

Purpose: There is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC.

Age-Specific Differences in the Risk of Colorectal Precursor Lesions Among Patients with Type 2 Diabetes Undergoing Surveillance Colonoscopy.

Background: The incidence rate of colorectal cancer (CRC) in young adults is rising in parallel with type 2 diabetes (T2D). The majority of CRC develop through two main subtypes of precursor lesions; adenomas and serrated lesions. The associations between age and T2D on development of precursor lesions remain uncertain.

Hot Mail: Temperature Exposure during Mail Return of an Immunochemical Fecal Occult Blood Test.

Background: Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening; however, high ambient temperatures were found to reduce test accuracy. More recently, proprietary globin stabilizers were added to FIT sample buffers to prevent temperature-associated hemoglobin (Hb) degradation, but their effectiveness remains uncertain. We aimed to determine the impact of high temperature (>30°C) on OC-Sensor FIT Hb concentration with current FITs, characterize FIT temperatures during mail transit, and determine impact of ambient temperature on FIT Hb concentration using data from a CRC screening program.

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).

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.

Detection of methylated BCAT1 and IKZF1 after curative-intent treatment as a prognostic indicator for colorectal cancer recurrence.

Background: The risk of recurrence after completion of curative-intent treatment of colorectal cancer (CRC) is hard to predict. Post-treatment assaying for circulating tumor DNA (ctDNA) is an encouraging approach for stratifying patients for therapy, but the prognostic value of this approach is less explored. This study aimed to determine if detection of methylated BCAT1 and IKZF1 following completion of initial treatment identified patients with a poorer recurrence-free survival (RFS).

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.

Screening and risk reducing surgery for endometrial or ovarian cancers in Lynch syndrome: a systematic review.

Objective: Lynch syndrome is a hereditary cancer syndrome caused by mismatch repair gene mutations, and female carriers are at an increased risk of endometrial and ovarian cancer. The best approach to screening is not yet clear and practice varies across countries and centers. We aimed to provide evidence to inform the best approach to screening and risk reduction.