Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening:A cross-sectional population-based analysis

Objective:Integration of risk stratification into fecal immunochemical test(FIT)might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer(CRC)screening.A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment(QRA)and FIT,FIT-only and QRA-only strategies in a CRC screening program in China.Methods:The study included 29,626 individuals aged 40-74 years and invited to participate in a CRC screening program in China.Participants were first invited to undertake QRA and one-time FIT(OC-sensor).Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy.Participation,detection rate,and resource demand for colonoscopy were calculated and compared.Results:Of the 29,626 invitees,20,203 completed the parallel combination,8,592 completed the QRA-only,and11 completed the FIT-only strategy.For the parallel combination,FIT-only,and QRA-only strategies,the overall positivity rates were 10.2%(2,928/28,806),5.4%(1,096/20,214),and 6.8%(1,944/28,795),respectively;the yield of advanced neoplasm per 10,000 invitees were 46.9[95%confidence interval(95%CI):39.8-55.4],36.8(95%CI:30.5-44.4),and 12.2(95%CI:8.8-16.8),respectively;the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7%(95%CI:4.0%-5.6%),9.9%(95%CI:8.3%-11.9%),and 1.9%(95%CI:1.3%-2.6%),respectively;the number of colonoscopies required to detect one advanced neoplasm was 11.4(95%CI:9.8-13.4),5.7(95%CI:4.8-6.7),and 28.4(95%CI:20.7-39.2),respectively.Conclusions:The parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.

The Diagnostic Value of Fecal Fusobacterium nucleatum Combined with FIT and CA199 in the Diagnosis of Colorectal Cancer

Objective:To analyze the diagnostic value of fecal Fusobacterium nucleatum detection,fecal immunochemical test(FIT),and carbohydrate antigen 19-9(CA19-9)detection for colorectal cancer(CRC).Method:Atotal of 78 CRC patients and 60 healthy individuals were enrolled in this study.Stool and blood samples were collected for the 3 diagnoses,and ROC curves were analyzed for diagnostic value.Result:The 3 diagnoses’positive detection rates in CRC samples were significantly higher than those of healthy samples(P<0.05).The combined CRC diagnoses showed significantly higher sensitivity as compared to individual fecal F.nucleatum detection(χ^(2)=6.495,P=0.011),FIT(χ^(2)=4.871,P=0.027),and serum CA19-9 detection(χ^(2)=7.371,P=0.007).The area under the ROC curve for fecal F.nucleatum detection was 0.63[95%confidence interval(CI)=1.124–6.238],with a sensitivity of 73.08%and specificity of 85.00%,whereas FIT was 0.65(95%CI=1.365–9.241),with a sensitivity of 51.28%and specificity of 96.67%,meanwhile,serum CA19-9 detection was 0.62(95%CI=1.517–12.342),with a sensitivity of 69.23%and specificity of 98.33%.The combined CRC diagnoses showed an area under the ROC curve of 0.76(95%CI=1.213–6.254),with a sensitivity of 87.18%and specificity of 70.00%.Conclusion:The combined diagnoses of fecal F.nucleatum detection,FIT,and serum CA19-9 detection can significantly improve the sensitivity and accuracy of CRC diagnosis,which has high clinical application value to provide guidance for clinical CRC screening and early intervention treatment.

Early colorectal cancer screening–no time to lose

In this editorial,we comment on the article entitled“Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?”by Agatsuma et al.Colorectal cancer(CRC)is emerging as an important health issue as its incidence continues to rise globally,adversely affecting the quality of life.Although the public has become more aware of CRC prevention,most patients lack screening awareness.Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC.However,due to the lack of awareness of the disease,most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.

Prediction of the severity of colorectal lesion by fecal hemoglobin concentration observed during previous test in the French screening program

BACKGROUND The rate of positive tests using fecal immunochemical test(FIT)does not decrease with subsequent campaigns,but the positive predictive value of advanced neoplasia significantly decreases in subsequent campaign after a first negative test.A relationship between the fecal hemoglobin concentration(Fhb)and the opportunity to detect a colorectal cancer in subsequent campaign has been shown.AIM To predict the severity of colorectal lesions based on Fhb measured during previous colorectal cancer screening campaign.METHODS This etiological study included 293750 patients aged 50-74,living in Auvergne-Rhone-Alpes(France).These patients completed at least two FIT[test_((-1))and test_((0))]between June 2015 and December 2019.Delay between test_((-1))and test_((0))was>1year and test_((-1))result was negative(<150 ngHb/mL).The severity of colorectal lesions diagnosed at test_((0))was described according to Fhb measured at test_((-1))[Fhb_((-1))].The relationship between the severity classified in seven ordinal categories and the predictive factors was analyzed in an ordered multivariate polytomous regression model.RESULTS The test_((0))positive rate was 4.0%,and the colonoscopy completion rate was 97.1%in 11594 patients who showed a positive test_((0)).The colonoscopy detection rate was 77.7%in those 11254 patients who underwent a colonoscopy.A total of 8748 colorectal lesions were detected(including 2182 low-risk-polyps,2400 high-riskpolyp,and 502 colorectal cancer).The colonoscopy detection rate varied significantly with Fhb_((-1))[0 ngHb/mL:75.6%,(0-50 ngHb/mL):77.3%,(50-100 ngHb/mL):88.7%,(100-150 ngHb/mL):90.3%;P=0.001].People with a Fhb_((-1))within(100-150 ngHb/mL)(P=0.001)were 2.6(2.2;3.0)times more likely to have a high severity level compared to those having a Fhb_((-1))value of zero.This risk was reduced by 20%in patients aged 55-59 compared to those aged<55[adjusted odds ratio:0.8(0.6;1.0)].CONCLUSION The study showed that higher Fhb_((-1))is correlated to an increased risk of severity of colorectal lesions.This risk of severity increased among first-time participants(age<55)and the elderly(≥70).To avoid the loss of chance in these age groups,the FIT positivity threshold should be reduced to 100 ngHb/mL.The other alternative would be to reduce the time between the two tests in these age groups from the current 2 years to 1 year.

A review of clinical research on using FIT screening for colorectal cancer

Colorectal cancer(CRC)has become the third most common cancer in the world and the second leading cause of death related to cancer.early screening of CRC can reduce its incidence rate and mortality.With the development of fecal immunochemical testing(FIT),FIT has been an important tool for screening CRC patients in high-risk groups worldwide.With the development of FIT,FIT has been an important tool for screening CRC patients in high-risk groups worldwide.In this paper,we describe the research progress of FIT screening for CRC.

Head-to-head comparison of the test performance of selfadministered qualitative vs. laboratory-based quantitative fecal immunochemical tests in detecting colorectal neoplasm

Background:Fecal immunochemical tests(FITs)are the most widely used non-invasive tests in colorectal cancer(CRC)screening.However,evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse.Methods:Based on a CRC screening trial(TARGET-C),we included 3144 pre-colonoscopy fecal samples,including 24 CRCs,230 advanced adenomas,622 non-advanced adenomas,and 2268 participants without significant findings at colonoscopy.Three selfadministered qualitative FITs(Pupu tube)with positivity thresholds of 8.0,14.4,or 20.8 mg hemoglobin(Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT(OC-Sensor)with a positivity threshold of 20 mg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory.The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds(for the quantitative FIT).Results:At the thresholds preset by the manufacturers,apart from the qualitative FIT-3,significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1(33.9%[95%CI:28.7–39.4%])and qualitative FIT-2(22.2%[95%CI:17.7–27.2%])compared to the quantitative FIT(11.7%[95%CI:8.4–15.8%]),while at a cost of significantly lower specificities.However,such difference was not observed for detecting CRC.For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly,there were no significant differences in terms of sensitivity,specificity,positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs,which was further evidenced in ROC analysis.Conclusions:Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer,such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates.Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates.

Novel multiplex stool-based assay for the detection of early-stage colon cancer in a Chinese population

BACKGROUND Stool DNA(sDNA)methylation analysis is a promising,noninvasive approach for colorectal cancer screening;however,reliable biomarkers for detecting early-stage colon cancer(ECC)are lacking,particularly in the Chinese population.AIM To identify a novel stool-based assay that can improve the effectiveness of ECC screening.METHODS A blinded case-control study was performed using archived stool samples from 125 ECC patients,and 125 control subjects with normal colonoscopy.The cohort was randomly divided into training and test sets at a 1.5:1 ratio.Targeted bisulfite sequencing(TBSeq)was conducted on five pairs of preoperative and postoperative sDNA samples from ECC patients to identify DNA methylation biomarkers,which were validated using pyrosequencing.By logistic regression analysis,a multiplex stool-based assay was developed in the training set,and the detection performance was further assessed in the test set and combined set.Theχ^(2)test was used to investigate the association of detection sensitivity with clinico-pathological features.RESULTS Following TBSeq,three hypermethylated cytosine-guanine sites were selected as biomarkers,including paired box 8,Ras-association domain family 1 and secreted frizzled-related protein 2,which differed between the groups and were involved in important cancer pathways.An sDNA panel containing the three biomarkers was constructed with a logistic model.Receiver operating characteristic(ROC)analysis revealed that this panel was superior to the fecal immunochemical test(FIT)or serum carcinoembryonic antigen for the detection of ECC.We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness.In the combined set,the sensitivity,specificity and area under the ROC curve for this multiplex assay were 80.0%,93.6%and 0.918,respectively,and the performance remained excellent in the subgroup analysis by tumor stage.In addition,the detection sensitivity did not differ with tumor site,tumor stage,histological differentiation,age or sex,but was significantly higher in T4 than in T1-3 stage tumors(P=0.041).CONCLUSION We identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT,which could detect ECC with high sensitivity and specificity throughout the colon,showing a promising application perspective.

Optimal Noninvasive Colon Cancer Screening Modality in Patients Not Receiving Colonoscopy

Colon cancer is the third most common among cancer deaths in the US for both men and women. The incidence of colonoscopy has been soaring in younger patients, which led to changes in recent United States Preventive Services Task Force (USPSTF) guidelines to reduce the age for screening from 50 years to 45 years. Demand for colonoscopy services is surging due to increased incidences of colorectal cancer (CRC) in the both aging and younger population. Increased referrals have led to an insufficient workforce in hospitals and long waiting lists. Further, results from colonoscopy reveal a low percentage of CRC or another severe bowel disease (SBD). Therefore, colon cancer screening is a growing concern, particularly in patients who otherwise have a very long-life expectancy, and who are most likely to benefit from screening. Another reason to boost CRC screening is to minimize the load on hospitals by reducing the patients that undergo colonoscopy unnecessarily because only a low percentage of CRC occurrence is observed in individuals undergoing colonoscopy. In recent years, there are a variety of screening options available for CRC. Noninvasive alternatives include fecal immunochemical test (FIT), multitarget stool DNA testing (MT-sDNA, available under the brand name Cologuard), computed tomography (CT) colonography (previously called virtual colonoscopy), guaiac-based fecal occult blood testing (gFOBT), and capsule colonoscopy (CC). These tests have varied the degree of evidence supporting their use. This study focuses on the most recent survey and efficacy of noninvasive methods to prevent and detect colorectal cancer (CRC).