Fecal immunochemical test-based colorectal cancer screening: The gender dilemma.

BACKGROUND: Despite differences between men and women in incidence of colorectal cancer (CRC) and its precursors, screening programs consistently use the same strategy for both genders. OBJECTIVE: The objective of this article is to illustrate the effects of gender-tailored screening, including the effects on miss rates of advanced neoplasia (AN). METHODS: Participants (age 50-75 years) in a colonoscopy screening program were asked to complete a fecal immunochemical test (FIT) before colonoscopy. Positivity rates, sensitivity and specificity for detection of AN at multiple cut-offs were determined. Absolute numbers of detected and missed AN per 1000 screenees were calculated. RESULTS: In total 1,256 individuals underwent FIT and colonoscopy, 51% male (median age 61 years; IQR 56-66) and 49% female (median age 60 years; IQR 55-65). At all cut-offs men had higher positivity rates than women, ranging from 3.8% to 10.8% versus 3.2% to 4.8%. Sensitivity for AN was higher in men than women; 40%-25% and 35%-22%, respectively. More AN were found and missed in absolute numbers in men at all cut-offs. CONCLUSION: More AN were both detected and missed in men compared to women at all cut-offs. Gender-tailored cut-offs could either level sensitivity in men and women (i.e., lower cut-off in women) or level the amount of missed lesions (i.e., lower cut-off in men).

Prevalence of serrated polyps and association with synchronous advanced neoplasia in screening colonoscopy.

BACKGROUND AND STUDY AIMS: Serrated polyps of the large intestine comprise a heterogeneous group of lesions with distinct histological and malignant features. The aim of the study was to estimate the prevalence of serrated polyp subtypes in a cohort of individuals undergoing screening colonoscopy, and to identify associations between the detection of serrated polyp subtypes and advanced neoplasia. PATIENTS AND METHODS: Data on serrated polyps, adenomas, and cancers were collected from participants of a randomized screening trial that compared colonoscopy with computed tomography colonography. Only data from participants in the colonoscopy arm were used. Logistic regression analyses were performed to identify associations between patients' age, sex, and prevalence of the different types of serrated polyps and to identify associations between the detection of these polyps and advanced neoplasia (defined as an adenoma ≥ 10 mm, villous component, high grade dysplasia or colorectal cancer). RESULTS: A total of 1426 screen-naïve individuals (51 % male) with a median age of 60 years (IQR 55 - 65) were included. The prevalence of hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs) was 23.8 %, 4.8 %, and 0.1 %, respectively. SSA/Ps comprised 7.3 % of all polyps. No differences based on age or sex were observed in the prevalence of SSA/Ps. Proximal and large (≥ 10 mm) hyperplastic polyps, as well as proximal and large (≥ 10 mm) SSA/Ps, were associated with synchronous advanced neoplasia. CONCLUSIONS: Serrated polyps, including SSA/Ps, were frequently encountered in routine screening colonoscopies. Large and proximal hyperplastic polyps, as well large and proximal SSA/Ps, were associated with advanced neoplasia.

Combining risk factors with faecal immunochemical test outcome for selecting CRC screenees for colonoscopy.

OBJECTIVE: Faecal immunochemical testing (FIT) is increasingly used in colorectal cancer (CRC) screening but has a less than perfect sensitivity. Combining risk stratification, based on established risk factors for advanced neoplasia, with the FIT result for allocating screenees to colonoscopy could increase the sensitivity and diagnostic yield of FIT-based screening. We explored the use of a risk prediction model in CRC screening. DESIGN: We collected data in the colonoscopy arm of the Colonoscopy or Colonography for Screening study, a multicentre screening trial. For this study 6600 randomly selected, asymptomatic men and women between 50 years and 75 years of age were invited to undergo colonoscopy. Screening participants were asked for one sample FIT (OC-sensor) and to complete a risk questionnaire prior to colonoscopy. Based on the questionnaire data and the FIT results, we developed a multivariable risk model with the following factors: total calcium intake, family history, age and FIT result. We evaluated goodness-of-fit, calibration and discrimination, and compared it with a model based on primary screening with FIT only. RESULTS: Of the 1426 screening participants, 1112 (78%) completed the questionnaire and FIT. Of these, 101 (9.1%) had advanced neoplasia. The risk based model significantly increased the goodness-of-fit compared with a model based on FIT only (p<0.001). Discrimination improved significantly with the risk-based model (area under the receiver operating characteristic (ROC) curve: from 0.69 to 0.76, (p=0.02)). Calibration was good (Hosmer-Lemeshow test; p=0.94). By offering colonoscopy to the 102 patients at highest risk, rather than to the 102 cases with a FIT result >50 ng/mL, 5 more cases of advanced neoplasia would be detected (net reclassification improvement 0.054, p=0.073). CONCLUSIONS: Adding risk based stratification increases the accuracy FIT-based CRC screening and could be used in preselection for colonoscopy in CRC screening programmes.

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.

Colorectal cancer risk factors in the detection of advanced adenoma and colorectal cancer.

Several risk factors for colorectal cancer (CRC) have been identified. If individuals with risk factors are more likely to harbor cancer or it precursors screening programs should be targeted toward this population. We evaluated the predictive value of colorectal cancer risk factors for the detection of advanced colorectal adenoma in a population based CRC colonoscopy screening program. Data were collected in a multicenter trial conducted in the Netherlands, in which 6600 asymptomatic men and women between 50 and 75 years were randomly selected from a population registry. They were invited to undergo a screening colonoscopy. Based on a review of the literature CRC risk factors were selected. Information on risk factors was obtained from screening attendees through a questionnaire. For each CRC risk factor, we estimated its odds ratio (OR) relative to the presence of advanced neoplasia as detected at colonoscopy. Of the 1426 screening participants who underwent a colonoscopy, 1236 (86%) completed the risk questionnaire. 110 participants (8.9%) had advanced neoplasia. The following risk factors were significantly associated with advanced neoplasia detected by colonoscopy: age (OR: 1.06 per year; 95% CI: 1.03-1.10), calcium intake (OR: 0.99 per mg; 95% CI: 0.99-1.00), positive CRC family history (OR: 1.55 per first degree family member; 95%CI: 1.11-2.16) and smoking (OR: 1.75; 95%CI: 1.09-2.82). Elderly screening participants, participants with lower calcium intake, a CRC family history, and smokers are at increased risk of harboring detectable advanced colorectal neoplasia at screening colonoscopy.

Differences in proximal serrated polyp detection among endoscopists are associated with variability in withdrawal time.

BACKGROUND: Insufficient detection of proximal serrated polyps (PSP) might explain the occurrence of a proportion of interval carcinomas in colonoscopy surveillance programs. OBJECTIVE: To compare PSP detection among endoscopists and to identify patient-related and endoscopist-related factors associated with PSP detection. DESIGN: Prospective study in unselected patients. SETTING: Colonoscopy screening program for colorectal cancer at two academic medical centers. PATIENTS: Asymptomatic consecutive screening participants (aged 50-75 years). INTERVENTION: Colonoscopies were performed by 5 experienced endoscopists. All detected polyps were removed. Multiple colonoscopy quality indicators were prospectively recorded. MAIN OUTCOME MEASUREMENTS: We compared PSP detection among endoscopists by calculating odds ratios (OR) with logistic regression analysis. Logistic regression also was used to identify patient features and colonoscopy factors associated with PSP detection. RESULTS: A total of 1354 patients underwent a complete screening colonoscopy: 1635 polyps were detected, of which 707 (43%) were adenomas and 685 (42%) were serrated polyps, including 215 PSPs. In 167 patients (12%) 1 or more PSPs were detected. The PSP detection rate differed significantly among endoscopists, ranging from 6% to 22% (P < .001). Longer withdrawal time (OR 1.12; 95% confidence interval, 1.10-1.16) was significantly associated with better PSP detection, whereas patient age, sex, and quality of bowel preparation were not. LIMITATIONS: Limited number of highly experienced endoscopists. CONCLUSION: The PSP detection rate differs among endoscopists. Longer withdrawal times are associated with better PSP detection, but patient features are not. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR1888.).

Reasons for participation and nonparticipation in colorectal cancer screening: a randomized trial of colonoscopy and CT colonography.

OBJECTIVES: We compared reported reasons for participation and nonparticipation in colorectal cancer (CRC) screening between colonoscopy and computed tomographic (CT) colonography in a randomized controlled trial. METHODS: We randomly invited 8,844 people for screening by colonoscopy or CT colonography. On a questionnaire, invitees indicated reasons for participation or nonparticipation and indicated the most decisive reason. RESULTS: The most frequently cited reasons to accept screening were early detection of precursor lesions and CRC, and contribution to science. The most frequently cited reasons to decline were the unpleasantness of the examination, the inconvenience of the preparation, a lack of symptoms, and "no time/too much effort." Among colonoscopy nonparticipants, elderly invitees cited inconvenience less often, and absence of symptoms more often, than did the group overall. The reason reported most frequently as the most decisive reason not to participate was the unpleasantness of the examination among colonoscopy nonparticipants, and "no time/too much effort" and lack of symptoms among CT colonography nonparticipants. CONCLUSIONS: In light of these results, future screening programs could tailor the information provided to invitees.

Adenoma detection with cap-assisted colonoscopy versus regular colonoscopy: a randomised controlled trial.

OBJECTIVE: Conventional colonoscopy (CC) is considered the reference standard for detection of colorectal neoplasia, but it can still miss a substantial number of adenomas. The use of a transparent plastic cap may improve colonic visualisation. Cap-assisted colonoscopy (CAC) was compared with CC for adenoma detection. Secondary outcomes were caecal intubation time, caecal intubation rate and the degree of discomfort of colonoscopy. DESIGN: This is a parallel, randomised, controlled trial at two centres. Asymptomatic participants (aged 50-75 years) in a primary colonoscopy screening programme were consecutively invited. Consenting subjects were 1:1 randomised to either CAC or CC. All colonoscopies were performed by experienced endoscopists (≥ 1000 colonoscopies) who were trained in CAC. Colonoscopy quality indicators were prospectively recorded. RESULTS: A total of 1380 participants were randomly allocated to CC (N=694) or CAC (N=686). Caecal intubation rate was comparable in the two groups (98% vs 99%; p=0.29). Caecal intubation time was significantly lower in the CAC group: 7.7 ± 5.0 min with CAC vs 8.9 ± 6.2 min with CC (p<0.001) (values mean ± SD). Adenoma detection rates of all endoscopists were ≥ 20%. The proportion of subjects with at least one adenoma was similar in the two groups (28% vs 28%; RR 0.98; 95% CI 0.82 to 1.16), as well as the mean number of adenomas per subject (0.49 ± 1.05 vs 0.50 ± 1.03; p=0.91). Detection of small size, flat and proximally located adenomas was comparable. CAC participants had lower Gloucester Comfort Scores during colonoscopy (2.2 ± 1.0 vs 2.0 ± 1.0; p=0.03). CONCLUSION: CAC does not improve adenoma detection, but does reduce caecal intubation time by more than 1 min and does lessen the degree of discomfort during colonoscopy.

Burden of colonoscopy compared to non-cathartic CT-colonography in a colorectal cancer screening programme: randomised controlled trial.

OBJECTIVE: CT-colonography has been suggested to be less burdensome for primary colorectal cancer (CRC) screening than colonoscopy. To compare the expected and perceived burden of both in a randomised trial. DESIGN: 8844 Dutch citizens aged 50-74 years were randomly invited for CRC screening with colonoscopy (n=5924) or CT-colonography (n=2920). Colonoscopy was performed after full colon lavage, or CT-colonography after limited bowel preparation (non-cathartic). All invitees were asked to complete the expected burden questionnaire before the procedure. All participants were invited to complete the perceived burden questionnaire 14 days later. Mean scores were calculated on 5-point scales. RESULTS: Expected burden: 2111 (36%) colonoscopy and 1199 (41%) CT-colonography invitees completed the expected burden questionnaire. Colonoscopy invitees expected the bowel preparation and screening procedure to be more burdensome than CT-colonography invitees: mean scores 3.0±1.1 vs 2.3±0.9 (p<0.001) and 3.1±1.1 vs 2.2±0.9 (p<0.001). Perceived burden: 1009/1276 (79%) colonoscopy and 801/982 (82%) CT-colonography participants completed the perceived burden questionnaire. The full screening procedure was reported as more burdensome in CT-colonography than in colonoscopy: 1.8±0.9 vs 2.0±0.9 (p<0.001). Drinking the bowel preparation resulted in a higher burden score in colonoscopy (3.0±1.3 vs 1.7±1.0, p<0.001) while related bowel movements were scored more burdensome in CT-colonography (2.0±1.0 vs 2.2±1.1, p<0.001). Most participants would probably or definitely take part in a next screening round: 96% for colonoscopy and 93% for CT-colonography (p=0.99). CONCLUSION: In a CRC screening programme, colonoscopy invitees expected the screening procedure and bowel preparation to be more burdensome than CT-colonography invitees. In participants, CT-colonography was scored as more burdensome than colonoscopy. Intended participation in a next screening round was comparable.

Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial.

BACKGROUND: Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography. METHODS: Members of the general population, aged 50-75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (≥10 mm) were offered colonoscopy; those with 6-9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829. FINDINGS: 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk [RR] 1·56, 95% CI 1·46-1·68; p<0·0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography (RR 1·46, 95% CI 1·06-2·03; p=0·02) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography (RR 0·91, 0·66-2·03; p=0·56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography, respectively (RR 0·74, 95% CI 0·53-1·03; p=0·07). Serious adverse events related to the screening procedure were post-polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group. INTERPRETATION: Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable. FUNDING: Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation.

Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives. METHODS AND DESIGN: 7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods. DISCUSSION: This study will provide further evidence to enable decision making in population screening for colorectal cancer. TRIAL REGISTRATION: Dutch trial register: NTR1829.