Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer

BackgroundQuantitative immunochemical faecal occult blood tests have become the recommended tests for colorectal cancer screening. The aim of this study was to complete our knowledge on the performance of one of the quantitative immunochemical tests available, FOB-Gold, and to propose a possible strategy for an organised screening programme.Patients and methodsWithin the French organised screening programme, 23,231 average-risk individuals, aged 50–74 performed both a 3-day Hemoccult test and a 1-day FOB-Gold test. Performances of the immunochemical test were evaluated at different cut-off levels.ResultsThe positivity rate for the Hemoccult was 2.1% and for the FOB-Gold varied between 4.6% (cut-off value of 100 ng/mL, the lowest studied cut-off) and 2.1% (cut-off value of 352 ng/mL). The number of colonoscopies decreased with increasing cut-off values by 21.5% (150 ng/mL), 35.4% (200 ng/mL) and 53.3% (352 ng/mL). The corresponding miss rate for CRC was respectively 6.4%, 11.1% and 22.2%, and for advanced adenoma respectively 16.3%, 29.2% and 43.6%. Compared with the reference cut-off for the FOB-Gold (100 ng/mL) the miss rate for Hemoccult was 53% for CRC and 77% for advanced adenoma.ConclusionThe study suggests that in countries with colonoscopy facilities compatible with a screening test positivity rate of up to 5%, use of a 1-day test with a cut-off value between 100 and 150 ng/mL could be the recommended strategy. Further increasing the cut-off value up to the same positivity rate as Hemoccult could be used in areas with limited access to colonoscopy.     

Strong subsite‐specific variation in detecting advanced adenomas by fecal immunochemical testing for hemoglobin

Fecal immunochemical tests (FITs) for hemoglobin are increasingly recommended and used in colorectal cancer (CRC) screening. We aimed to provide a detailed assessment of the sensitivity of FIT according to type and subsite of neoplasms in a true screening setting. A quantitative FIT (FOB Gold, Sentinel Diagnostics, Milano, Italy) was applied prior to colonoscopy by 3,466 participants of the German screening colonoscopy program. Subsite specific sensitivity for various types of colorectal neoplasms was derived by comparing FIT results with findings at screening colonoscopy. The most advanced finding at colonoscopy was CRC, advanced adenoma, and nonadvanced adenoma in 29, 354 and 686 cases, respectively. Per‐adenoma sensitivity for large advanced adenomas (>1 cm) strongly varied by location (p < 0.001): cecum: 0/14 (0%), ascending colon and right flexure: 11/43 (26%), transverse colon and left flexure: 2/14 (14%), descending colon: 7/12 (58%), sigmoid colon: 47/92 (51%), rectum: 14/39 (36%). By contrast, the FIT detected all of 5 proximal CRC and 23 out of 24 (96%) distal CRCs, whereas per‐adenoma sensitivity of both proximal (17/259, 7%) and distal nonadvanced adenomas (20/237, 8%) essentially equaled the false positivity rate among those without neoplasms (152/2,397, 6%). In conclusion, we found a very large gradient of subsite specific FIT sensitivity for detecting large advanced adenomas ranging from 0% for advanced adenomas located in the cecum to >50% for those located in the descending or sigmoid colon. By contrast, FIT sensitivity was uniformly excellent for CRC and uniformly poor for nonadvanced adenomas, regardless of their location.     

Lack of Association between Red Meat Consumption and a Positive Fecal Immunochemical Colorectal Cancer Screening Test in Khon Kaen,Thailand: a Population- Based Randomized Controlled Trial

Background: There is convincing evidence from epidemiological studies that meat consumption increases colorectal cancer (CRC) risk. However, assessment of any association with a positive fecal immunochemical test (FIT) in CRC screening has been limited. If a link could be shown this might be helpful for establishing a risk group for colonoscopy. Objective: This study aimed to assess any association between meat consumption and other lifestyle factors and a positive FIT result in a Thai population. Methods: A cross-sectional analytical study was conducted with 1,167 participants in a population-based randomized controlled trial. CRC was screened from May 2016 - February 2017. Subjects aged 45-74 years who met the eligibility criteria were randomly allocated to the study arm. A positive FIT was determined with cut-off 100 ng/mL. Multiple logistic regression was used to analyze any relationship between lifestyle factors and a positive FIT. Result: The total number of subjects was 1,060 (90.8% return rate of FIT). With FIT100, FIT150, and FIT200, positive tests were found in 92 (8.68%), 74 (6.98%), and 60 (5.66%), respectively. No significant associations were noted with any of the variables, except for being aged 60-74 years (ORadj = 1.62, 95% CI: 1.03-2.54) Borderline significance was observed for high consumption of vegetables (ORadj = 0.62, 95% CI: 0.36-1.07) and being male (ORadj = 1.39, 95% CI: 0.87-2.22). Conclusion: Despite the evidence from the literature, no association was here found between a positive FIT result and meat consumption or other well-established lifestyle parameters. Being aged 60-74 years was a risk factor which should be taken into account in CRC screening strategy in countries like Thailand with limited access to endoscopy.     

Preferences and Acceptance of Colorectal Cancer Screening in Thailand

Colorectal cancer (CRC) is now common in Thailand with an increase in incidence over time. Health authoritiesare planning to implement a nationwide CRC screening program using fecal immunochemical test (FIT) as aprimary screening tool. This study aimed to estimate preferences and acceptance of FIT and colonoscopy, explorefactors influencing the acceptance, and investigate reasons behind choosing and rejecting to screen before theprogram was implemented. Patients aged 50-69, visiting the primary care unit during the study period, wereinvited to join this study. Patients with a history of cancer or past CRC screening were excluded. Face-to-faceinterviews were conducted. Subjects were informed about CRC and the screening tests: FIT and colonoscopy.Then, they were asked for their opinions regarding the screening. The total number of subjects was 437 (86.7%response rate). Fifty-eight percent were females. The median age was 58 years. FIT was accepted by 74.1% ofsubjects compared to 55.6% for colonoscopy. The acceptance of colonoscopy was associated with perceivedsusceptibility to CRC and family history of cancer. No symptoms, unwilling to screen, healthy, too busy and anxiousabout diagnosis were reasons for refusing to screen. FIT was preferred for its simplicity and non-invasivenesscompared with colonoscopy. Those rejecting FIT expressed a strong preference for colonoscopy. Subjects chosecolonoscopy because of its accuracy; it was refused for the process and complications. If the screening programis implemented for the entire target population in Thailand, we estimate that 106,546 will have a positive FIT,between 8,618 and 12,749 identified with advanced adenoma and between 2,645 and 3,912 identified with CRCin the first round of the program.     

Prospective multicenter evaluation of fecal tumor pyruvate kinase type M2 (M2-PK) as a screening biomarker for colorectal neoplasia

Proliferating cells, particularly the tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed M2-PK. It's a direct target of several oncoproteins; the determination of fecal tumor pyruvate kinase type M2 (M2-PK) might be another promising tool for colorectal cancer (CRC) screening. In this study, we have evaluated fecal M2-PK as a screening biomarker for colorectal neoplasia. It was compared against fecal occult blood (FOB) and colonoscopy. Three hundred and seventeen consecutive subjects from 4 different centers were included. Stool specimens were collected before purgation, processed appropriately and were tested for FOB and quantitatively analyzed for M2-PK. Colonoscopies were performed by experienced endoscopists who were unaware of fecal assay results. At cutoff value of 4 U/ml, fecal M2-PK assay had a sensitivity, specificity, PPV and NPV of 81.1, 86.7, 71.1 and 61.9% respectively for diagnosing CRC whereas FOBT showed a sensitivity of 36.5%, specificity of 92.2%, PPV of 72.9% and NPV of 71.5% for CRC. Such low specificity of fecal M2-PK will lead to unacceptably high number of false positives if it is used for mass CRC screening, leading to unindicated colonoscopies with its associated inconveniences, risks and costs. CRC screening test must have high specificity; a high sensitivity is not as vital. To conclude, M2-PK was found to be a poor screening biomarker for CR neoplasia in a subject population at above average risk based on its prospective comparison with colonoscopy. These marginal performance characteristics do not permit its use as a screening tool for CR neoplasia in present clinical settings.     

Colorectal Cancer Screening among Government Servants in Brunei Darussalam

Background: This study concerns uptake and results of colorectal cancer (CRC) screening of governmentservant as part of the Health Screening Program that was conducted in Brunei Darussalam in 2009. Materialsand Methods: Government servants above the age of 40 or with family history of CRC were screened with a singlefecal occult blood test (FIT, immunohistochemistry). Among 11,576 eligible subjects, 7,360 (66.9%) returned theirspecimen. Subjects with positive family history of CRC (n=329) or polyps (n=135) were advised to attend clinicsto arrange screening. All the subjects with positive FIT (n=142, 1.9%) were referred to the endoscopy unit forcounselling for screening colonoscopy. Results: Overall only 17.7% of eligible subjects attended for screening;54.9% (n=79/142) of positive FIT, 8.8% (n=29/329) of positive family history of CRC and none with history ofpolyps (n=0/135). Of these, only 54 patients (50.5%) agreed for colonoscopy, 52 (48.6%) declined as they wereasymptomatic, and one was not offered (0.9%) due to his very young age. On screening colonoscopy, 12.9% (n=7)had advanced lesions including a sigmoid carcinoma in situ and six advanced polyps. The other findings includednon advanced polyps (n=21), diverticular (n=11) and hemorrhoids (n=26). One patient who missed his screeningcolonoscopy appointment re-presented two years later and was diagnosed with advanced right sided CRC. Allthe advanced lesions were detected in patients with positive FIT, giving a yield of 20.5% for advanced lesionsincluding cancers in the 5.1% FIT positive subjects. Conclusions: Our study showed screening for CRC evenwith a single FIT was effective. However, the uptake rate was poor with just over half of the patients agreeing toscreening colonoscopy. Measures to increase public awareness are important. Since one limitation of our studywas the relatively small sample size, larger studies should be conduced in future.     

Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy

There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005–2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT.     

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml⁻¹, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml⁻¹, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml⁻¹ provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.     

Fecal immunochemical test accuracy in familial risk colorectal cancer screening

There is little information on fecal immunochemical test (FIT) in familial risk colorectal cancer (CRC) screening. Our study assesses FIT accuracy, number needed to scope (NNS) and cost to detect a CRC and an advanced neoplasia (AN) in this setting. We performed a multicentric, prospective, double‐blind study of diagnostic tests on individuals with first‐degree relatives (FDRs) with CRC submitted to screening colonoscopy. Two stool samples were collected and fecal hemoglobin in the first sample (FIT1) and the highest in both samples (FITmax) were determined. Areas under the curve (AUC) for CRC and AN as well as the best FIT1 and FITmax cutoff value for CRC were determined. At this threshold, NNS and the cost per lesion detected were calculated. A total of 595 individuals were included (one FDR > 60 years, 413; two FDR or one ≤ 60 years, 182). AN and CRC were found in 64 (10.8%) and six (1%) patients, respectively. For CRC diagnosis, FIT1 AUC was 0.96 [95% confidence interval (CI): 0.95–0.98] and FITmax AUC was 0.95 (95% CI: 0.93–0.97). For AN diagnosis, FIT1 and FITmax AUC were 0.74 (95% CI: 0.66–0.82). The best cutoff point for CRC was 115. At this threshold, the NNS to detect a CRC was 5.67 and 7.67, and the cost per CRC was 1,064€ and 1591.33€ on FIT1 and FITmax strategies, respectively. FIT shows high accuracy to detect CRC in familial CRC screening. Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.     

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43–57) vs 55 years (IQR 51–62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P = .0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P < .0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P < .0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.     

Uptake of faecal immunochemical test screening among nonparticipants in a flexible sigmoidoscopy screening programme

Screening programmes based on single modality testing may prevent individuals with a preference for a different test from participating. We conducted a population-based trial to determine whether nonparticipants in flexible sigmoidoscopy (FS) screening were willing to attend faecal immunochemical test (FIT) screening. In total, 8,407 subjects were invited in a primary FS screening programme. Invitees did not know at the time of FS invitation that nonparticipants would be offered FIT screening. A total of 4,407 nonparticipants of FS screening were invited for FIT screening (cut-off 50 ng haemoglobin/ml). The participation rate to FS screening was 31% [95% confidence interval (CI): 30-32%]. Among the FS nonparticipants 25% (CI: 24-26%) did attended FIT screening. The participation rate of the two-stage recruitment for FS and FIT screening was 45% (CI: 44-46%). FIT screenees were older (p = 0.02), more often women (p < 0.001) and had a lower social economic status (p = 0.01) than FS screenees. The detection rate (DR) for advanced adenoma was 3.5% (CI: 2.5-4.8%), and for colorectal cancer (CRC) it was 0.3% (CI: 0.1-0.8%) among participants to FIT screening. The DR of the two-stage recruitment was 6.1% (n = 202) for an advanced adenoma and 0.5% (n = 16) for a CRC. In conclusion, offering FIT screening to nonparticipants in a FS screening programme increases the overall participation rate considerably, as a quarter of nonparticipants of FS screening was willing to attend FIT screening. The participation rate remains lower for primary FIT screening in the same population (62%). Women in the target population were more likely to refuse FS than FIT screening. Countries introducing FS screening should be aware of these preferences.     

定量粪便免疫化学试验筛查阈值对结直肠肿瘤早筛价值的影响

目的:分析定量粪便免疫化学试验（fecal immunochemistry test，FIT）筛查阈值对体检人群结直肠肿瘤早筛价值的影响。方法:以2017年07月至2021年06月在我院接受定量FIT检测并行肠镜检查的1 267例人群为研究对象，比较不同性质肿瘤的定量FIT数值和阳性率。通过Logistic 回归和受试者工作特征（receiver operating characteristic，ROC）曲线分析比较不同性别、年龄和不同阳性阈值下定量FIT对进展期肿瘤的筛检效能。结果:定量 FIT筛查阳性率为4.7%，阳性人群肠镜依从性为22.2%。结直肠癌患者的定量FIT数值高于进展期腺瘤和其他肠镜结果。当定量FIT水平为100~199 μg/L、200~299 μg/L、300~499 μg/L和500 μg/L以上时，患进展期肿瘤的风险分别是<100 μg/L时的4.296倍、4.121倍、6.506倍和10.474倍。不同阳性阈值下，FIT阳性组进展期肿瘤检出率均高于阴性组，且在男性和50~75岁人群中均有统计学差异。在100 μg/L时的比值比（odds ratio，OR）最大（总体OR=6.817，95%CI:2.727~17.040；男性OR=5.570，95%CI:2.198~14.115；50~75岁OR=10.178，95%CI:3.158~32.803）。此时，定量FIT对进展期肿瘤的灵敏度分别为94.7%、93.0%、96.2%，特异度分别为27.6%、29.6%、28.7%。当阳性阈值由100 μg/L升高至500 μg/L时，FIT诊断进展期肿瘤的灵敏度下降，特异度升高，但阳性预测值和阴性预测值变化不大。结论:定量FIT阳性阈值在100 μg/L时筛查进展期结直肠肿瘤的灵敏度较好，但特异度较低，是应用在体检人群伺机性筛查中较好的结直肠肿瘤早筛参考指标。     

Risk factors for false positive and for false negative test results in screening with fecal occult blood testing

Differences in the risk of a false negative or a false positive fecal immunochemical test (FIT) across subgroups may affect optimal screening strategies. We evaluate whether subgroups are at increased risk of a false positive or a false negative FIT result, whether such variability in risk is related to differences in FIT sensitivity and specificity or to differences in prior CRC risk. Randomly selected, asymptomatic individuals were invited to undergo colonoscopy. Participants were asked to undergo one sample FIT and to complete a risk questionnaire. We identified patient characteristics associated with a false negative and false positive FIT results using logistic regression. We focused on statistically significant differences as well as on variables influencing the false positive or negative risk for which the odds ratio exceeded 1.25. Of the 1,426 screening participants, 1,112 (78%) completed FIT and the questionnaire; 101 (9.1%) had advanced neoplasia. 102 Individuals were FIT positive, 65 (64%) had a false negative FIT result and 66 (65%) a false positive FIT result. Participants at higher age and smokers had a significantly higher risk of a false negative FIT result. Males were at increased risk of a false positive result, so were smokers and regular NSAID users. FIT sensitivity was lower in females. Specificity was lower for males, smokers and regular NSAID users. FIT sensitivity was lower in women. FIT specificity was lower in males, smokers and regular NSAID users. Our results can be used for further evidence based individualization of screening strategies.     

Factors associated with false-positive fecal immunochemical tests in a large German colorectal cancer screening study

In recent years fecal immunochemical tests (FITs) have been offered as a primary screening test for colorectal cancer (CRC) in a growing number of countries. Our study aims to identify factors associated with apparently false-positive results of FITs. In this cross-sectional study within the German population-based screening colonoscopy program, participants were invited to provide a stool sample for FIT prior to colonoscopy. Four thousand six hundred and fifty six participants aged 50–79 years with no known history of CRC or inflammatory bowel disease (IBD) and no findings of neoplasms at screening colonoscopy were included in the current analyses. Main outcome measures were rates and factors associated with apparently false-positive FIT results. Apparently false-positive FIT results were found for 378 participants (8.1%). Male sex (OR = 1.30, 95%CI 1.03, 1.62), age ≥65 years (OR = 1.27, 95%CI 1.01, 1.59), a BMI ≥30 kg/m² (OR = 1.81, 95%CI 1.36, 2.40), current smoking (OR = 1.63, 95%CI 1.18, 2.25), use of aspirin (OR = 1.36, 95%CI 1.02, 1.82) and a new diagnosis of IBD (OR = 9.13, 95%CI 2.18, 38.19) or other non-neoplastic findings (OR = 1.86, 95%CI 1.37, 2.51) at screening colonoscopy were independently associated with significantly increased odds of a positive FIT. Although considered false positive in the context of CRC screening, the identified factors associated with apparently false-positive FIT results are known risk factors for and may point to conditions other than colorectal neoplasms that may be potential sources of gastrointestinal bleeding, potentially requiring further medical follow up.     

Making colonoscopy-based screening more efficient: A “gateopener” approach

Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy-based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a “gateopener” for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single (“gateopener”) FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such “gateopener screening” (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10-times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%-51% and 59%-65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a “gateopener” low-threshold FIT would substantially enhance efficiency of colonoscopy screening.     

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.     

Seasonal variations do not affect the superiority of fecal immunochemical tests over guaiac tests for colorectal cancer screening

The aim of this study was to compare the seasonal variation in performance of a faecal immunochemical test for haemoglobin (FIT) and a guaiac test (gFOBT) for colorectal cancer screening. From June 2009 to May 2011, 18,290 screening participants (50–74 years old) performed OC‐SENSOR quantitative FIT (1 sample) and Hemoccult II gFOBT (3 stool samples with 2 spots/sample). Referral for colonoscopy required a minimum of one positive spot (gFOBT), or a positive FIT [cut‐off 150 ng haemoglobin/mL buffer (i.e. 30 μg haemoglobin/g feces)]. The performance of tests for detection of advanced neoplasia was compared according to seasons using Receiver Operating Characteristics (ROC) curves, at various FIT cut‐off values. The positivity rate of FIT was significantly lower in the summer compared with other seasons (2.3% versus 3.0%, p = 0.03), whilst the positivity rate of gFOBT increased in the autumn (1.8% versus 1.5%, p = 0.11). FIT was clinically more effective than gFOBT over the four season‐specific ROC curves. At the cut‐off concentration used in the study, the season‐specific FIT/gFOBT ratios for true positive rates were: 2.8 (Autumn), 2.5 (Winter), 3.0 (Spring), 3.7 (Summer), and for false positive rates: 1.2 (Autumn), 1.5 (Winter), 1.8 (Spring), 0.9 (Summer). Therefore, in this study with this cut‐off concentration and in spite of lower positivity rate in summer, the seasonal variations of performance of OC‐SENSOR FIT led to improved gain in specificity in the summer, without a decrease in gain in sensitivity compared with gFOBT.     

Willingness to Pay for Colorectal Cancer Screening and Effect of Copayment in Southern Thailand

Background: The incidence rate of colorectal cancer in Thailand is increasing. Hence, the nationwide screeningprogramme with copayment is being considered. There are two proposed screening alternatives: annual fecalimmunochemical test (FIT) and once-in-10-year colonoscopy. A copayment for FIT is 60 Thai baht (THB) per test(≈ 1.7 USD); a copayment for colonoscopy is 2,300 THB per test (≈ 65.5 USD). Methods: The willingness to pay(WTP) technique, which is theoretically founded on a cost-benefit analysis, was used to assess an effect of copayment onthe uptake. Subjects were patients aged 50-69 years without cancer or screening experience. WTP for the proposedtests was elicited. Results: Nearly two thirds of subjects were willing to pay for FIT. Less than half of subjects werewilling to pay for colonoscopy. Among them, median WTP for both tests was greater than the proposed copayments.In a probit model, knowing CRC patient and presence of companion were associated with non-zero WTP for FIT.Presence of companion, female, and family history of cancer were associated with non-zero WTP for colonoscopy.After adjustment for starting price in the linear model, marital status, drinking behavior, and risk attitude were associatedwith WTP. None of factors was significant for colonoscopy. Uptake decreased as levels of copayment increased.At proposed copayments, the uptake rates of 59.8% and 21.6% were estimated for colonoscopy and FIT respectively.The demand for FIT was price inelastic; the demand for colonoscopy was price elastic. Estimates of optimal copaymentwere 62.1 THB for FIT and 460.2 THB for colonoscopy. At the optimal copayment, uptake rates would be 59.8%for FIT and 42.3% for colonoscopy.Conclusion(s): More subjects were willing to pay for FIT than for colonoscopy(59.0% versus 46.5%). The estimated uptake rates were 59.8% and 21.6% for colonoscopy and FIT at the proposedcopayments.     

Screening strategies for colorectal cancer among patients with nonalcoholic fatty liver disease and family history

Patients with nonalcoholic fatty liver disease (NAFLD) and family history of colorectal cancer (CRC) are at higher risks but how they should be screened remains uncertain. Hence, we evaluated the cost‐effectiveness of CRC screening among patients with NAFLD and family history by different strategies. A hypothetical population of 100,000 subjects aged 40–75 years receive: (i) yearly fecal immunochemical test (FIT) at 50 years; (ii) flexible sigmoidoscopy (FS) every 5 years at 50 years; (iii) colonoscopy 10 yearly at 50 years; (iv) colonoscopy 10 yearly at 50 years among those with family history/NAFLD and yearly FIT at 50 years among those without; (v) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and yearly FIT at 50 years among those without and (vi) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The incremental cost‐effectiveness ratio (ICER) was studied by Markov modeling. It was found that colonoscopy, FS and FIT reduced incidence of CRC by 49.5, 26.3 and 23.6%, respectively. Using strategies 4, 5 and 6, the corresponding reduction in CRC incidence was 29.9, 30.9 and 69.3% for family history, and 33.2, 34.7 and 69.8% for NAFLD. Compared with no screening, strategies 4 (US$1,018/life‐year saved) and 5 (US$7,485) for family history offered the lowest ICER, whilst strategy 4 (US$5,877) for NAFLD was the most cost‐effective. These findings were robust when assessed with a wide range of deterministic sensitivity analyses around the base case. These indicated that screening patients with family history or NAFLD by colonoscopy at 50 years was economically favorable.     

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

ObjectiveIntegration 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.MethodsThe 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.ResultsOf the 29,626 invitees, 20,203 completed the parallel combination, 8,592 completed the QRA-only, and 11 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.ConclusionsThe parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.