The impact of stratifying by family history in colorectal cancer screening programs

In the province‐wide colorectal cancer (CRC) screening program in Ontario, Canada, individuals with a family history of CRC are offered colonoscopy screening and those without are offered guaiac fecal occult blood testing (gFOBT, Hemoccult II). We used microsimulation modeling to estimate the cumulative number of CRC deaths prevented and colonoscopies performed between 2008 and 2038 with this family history‐based screening program, compared to a regular gFOBT program. In both programs, we assumed screening uptake increased from 30% (participation level in 2008 before the program was launched) to 60%. We assumed that 11% of the population had a family history, defined as having at least one first‐degree relative diagnosed with CRC. The programs offered screening between age 50 and 74 years, every two years for gFOBT, and every ten years for colonoscopy. Compared to opportunistic screening (2008 participation level kept constant at 30%), the gFOBT program cumulatively prevented 6,700 more CRC deaths and required 570,000 additional colonoscopies by 2038. The family history‐based screening program increased these numbers to 9,300 and 1,100,000, a 40% and 93% increase, respectively. If biennial gFOBT was replaced with biennial fecal immunochemical test (FIT), annual Hemoccult Sensa or five‐yearly sigmoidoscopy screening, both the added benefits and colonoscopies required would decrease. A biennial gFOBT screening program that identifies individuals with a family history of CRC and recommends them to undergo colonoscopy screening would prevent 40% (range in sensitivity analyses: 20–51%) additional deaths while requiring 93% (range: 43–116%) additional colonoscopies, compared to a regular gFOBT screening program.     

Changes in the choice of colorectal cancer screening tests in primary care settings from 7,845 prospectively collected surveys

Purpose

Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. This study examined factors influencing the choice of participants between colonoscopy and fecal immunochemical test (FIT) in a screening program and the impact of an unbiased educational session on influencing this decision.

Methods

Data from 7,845 participants who underwent screening between May 2008 and April 2011 was analyzed. Binary logistic regression and multinomial regression were performed to calculate the odds of selection of colonoscopy instead of FIT and the impact of the educational session on final participant choice, respectively.

Results

Of the 7,845 participants, 4,796 (61?%) underwent FIT and 3,049 (39?%) underwent colonoscopy. A significant number of participants changed their initial choice after the educational session, with 27.1?% changing to FIT from colonoscopy and 8?% changing from FIT to colonoscopy. Age, educational level, occupation, income, family history of CRC, perception of risk of CRC, and perceptions regarding CRC screening were significantly different among the groups choosing FIT and colonoscopy. Family history of CRC and high self-perception of CRC risk resulted in higher odds of choosing colonoscopy, whereas older age, single marital status, and negative perception of CRC screening resulted in lower odds. Perceptions of overall health status, occupation, low income, younger age, and negative perceptions of CRC screening were associated with higher odds of change in screening choice.

Conclusions

Those at higher odds of changing CRC screening options should be supported with more detailed explanations by primary care physicians to secure a more informed and considered choice.     

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.     

High prevalence of human papillomavirus infection in the female population of Guatemala

The costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost‐effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN‐colon microsimulation model to estimate the costs and life‐years gained of screening persons aged 50–80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp ≥6 mm and (iv) a suspected polyp ≥10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life‐years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps ≥6 mm. For this strategy to be as cost‐effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39–47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10‐yearly colonoscopy, where we compared to different intervals of colonoscopy screening. © 2008 Wiley‐Liss, Inc.     

Impact of adenoma detection on the benefit of faecal testing vs. colonoscopy for colorectal cancer

Colonoscopy quality, as measured by adenoma detection rates, varies widely across providers and is inversely related to patients' post‐colonoscopy cancer risk. This has unknown consequences for the benefits of faecal immunochemical testing (FIT) vs. primary colonoscopy screening for colorectal cancer. Using an established microsimulation model, we predicted the lifetime colorectal cancer incidence and mortality benefits of annual FIT vs. 10‐yearly colonoscopy screening at differing ADR levels (quintiles; averages 15.3–38.7%), with colonoscopy performance assumptions estimated from community‐based data on physician ADRs and patients' post‐colonoscopy risk of cancer. For patients receiving FIT screening with follow‐up colonoscopy by physicians from the highest ADR quintile, simulated lifetime cancer incidence and mortality were 28.8 and 5.4 per 1,000, respectively, vs. 20.6 and 4.4 for primary colonoscopy screening (risk ratios, RR = 1.40; 95% probability interval (PI), 1.19–1.71 for incidence, and RR = 1.22; 95%PI, 1.02–1.54 for mortality). With every 5% point ADR decrease, lifetime cancer incidence was predicted to increase on average 9.0% for FIT vs. 12.3% for colonoscopy, and mortality increased 9.9% vs. 13.3%. In ADR quintile 1, simulated mortality was lower for FIT than colonoscopy screening (10.1 vs. 11.8; RR = 0.85; 95%PI, 0.83–0.90), while incidences were more similar. This suggests that relative cancer incidence and mortality reductions for FIT vs. colonoscopy screening may differ by ADR, with fewer predicted deaths with colonoscopy screening in higher ADR settings and fewer deaths with annual FIT screening in lower ADR settings.     

Disparities in cancer screening in individuals with a family history of breast or colorectal cancer

BACKGROUND:

Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population‐based survey.

METHODS:

By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years.

RESULTS:

The authors found no significant BC screening disparities by race/ethnicity or income in the family history risk groups. Racial/ethnic disparities were more evident in CRC screening, and the Latino‐white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino‐white difference in CRC screening (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11‐0.60) was more substantial than that for individuals with no family history (OR, 0.74; 95% CI, 0.59‐0.92).

CONCLUSIONS:

Knowledge of their family history widened the Latino‐white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino‐white screening disparity in Latinos most susceptible to CRC. Cancer 2011;. © 2011 American Cancer Society.     

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.     

Colorectal cancer screening for average‐risk adults: 2018 guideline update from the American Cancer Society

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model‐recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high‐sensitivity stool‐based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average‐risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high‐sensitivity, guaiac‐based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250–281 . © 2018 American Cancer Society .     

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test,Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden

BackgroundFecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT⁺) screening population and thereby reduce the colonoscopy burden.Materials and methodsFrom the Danish National Colorectal Cancer Screening Program, 4048 FIT⁺ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling.ResultsThe discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs.ConclusionA screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.     

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.     

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.     

Evaluation of the benefits,harms and cost‐effectiveness of potential alternatives to iFOBT testing for colorectal cancer screening in Australia

The Australian National Bowel Cancer Screening Program (NBCSP) will fully roll‐out 2‐yearly screening using the immunochemical Faecal Occult Blood Testing (iFOBT) in people aged 50 to 74 years by 2020. In this study, we aimed to estimate the comparative health benefits, harms, and cost‐effectiveness of screening with iFOBT, versus other potential alternative or adjunctive technologies. A comprehensive validated microsimulation model, Policy1‐Bowel, was used to simulate a total of 13 screening approaches involving use of iFOBT, colonoscopy, sigmoidoscopy, computed tomographic colonography (CTC), faecal DNA (fDNA) and plasma DNA (pDNA), in people aged 50 to 74 years. All strategies were evaluated in three scenarios: (i) perfect adherence, (ii) high (but imperfect) adherence, and (iii) low adherence. When assuming perfect adherence, the most effective strategies involved using iFOBT (annually, or biennially with/without adjunct sigmoidoscopy either at 50, or at 54, 64 and 74 years for individuals with negative iFOBT), or colonoscopy (10‐yearly, or once‐off at 50 years combined with biennial iFOBT). Colorectal cancer incidence (mortality) reductions for these strategies were 51–67(74–80)% in comparison with no screening; 2‐yearly iFOBT screening (i.e. the NBCSP) would be associated with reductions of 51(74)%. Only 2‐yearly iFOBT screening was found to be cost‐effective in all scenarios in context of an indicative willingness‐to‐pay threshold of A$50,000/life‐year saved (LYS); this strategy was associated with an incremental cost‐effectiveness ratio of A$2,984/LYS–A$5,981/LYS (depending on adherence). The fully rolled‐out NBCSP is highly cost‐effective, and is also one of the most effective approaches for bowel cancer screening in Australia.     

The Optimal Cut-Off Level of The Fecal Immunochemical Test For Colorectal Cancer Screening in a Country with Limited Colonoscopy Resources: A Multi-Center Study from Thailand

Background: Selecting the cut-off point for the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening programs is of prime importance. The balance between the test performance for detecting advanced neoplasia and the available colonoscopy resources should be considered. We aimed to identify the optimal cut-off of FIT for advanced neoplasia in order to minimize colonoscopy burden. Methods: We conducted a multi-center study in 6 hospitals from diverse regions of Thailand. Asymptomatic participants, aged 50-75 years, were tested with one-time quantitative FIT (OC-SENSOR, Eiken Chemical Co.,Ltd., Tokyo, Japan) and all participants underwent colonoscopy. We assessed test performance in detecting advanced neoplasia (advanced adenoma and CRC) and measured the burden of colonoscopy with different cut-offs [25 (FIT25), 50 (FIT50), 100 (FIT100), 150 (FIT150), and 200 (FIT200)ng/ml]. Results: Among 1,479 participants, advanced neoplasia and CRC were found in 137 (9.3%) and 14 (0.9%), respectively. From FIT25 to FIT200, the positivity rate decreased from 18% to 4.9%. For advanced neoplasia, an increased cut-off decreased sensitivity from 42.3% to 16.8% but increased specificity from 84.2% to 96.3%. The increased cut-off increased the positive predictive value (PPV) from 21.5% to 31.5%. However, all cut-off points provided a high negative predictive value (NPV) (>90%). For CRC, the miss rate for FIT25 to FIT 150 was the same (n=3, 21%), whereas that with FIT200 increased to 35% (n=5). Conclusions: In a country with limited-colonoscopy resources, using FIT150 may be preferred because it offers both high PPV and NPV for advanced neoplasia detection. It could also decrease colonoscopy workload, while maintaining a CRC miss rate similar to those with lower cut-offs.     

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.     

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.     

A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test,despite lower compliance rate. A prospective,controlled, feasibility study

Immunochemical fecal occult blood test (FIT) is a new colorectal cancer (CRC) screening method already recommended by the American screening guidelines. We aimed to test the feasibility of FIT as compared to guaiac fecal occult blood test (G‐FOBT) in a large urban population of Tel Aviv. Average‐risk persons, aged 50–75 years, were offered FIT or G‐FOBT after randomization according to the socioeconomic status of their clinics. Participants with positive tests underwent colonoscopy. Participants were followed through the Cancer Registry 2 years after the study. Hemoccult SENSA? and OC‐MICRO? (three samples, 70 ng/ml threshold) were used. FIT was offered to 4,657 persons (Group A) and G‐FOBT to 7,880 persons (Group B). Participation rate was 25.9% and 28.8% in Group A and B, respectively (p < 0.001). Positivity rate in Group A and B was 12.7% and 3.9%, respectively (p < 0.001). Cancer found in six (0.49%) and eight (0.35%) patients of Group A and B, respectively (NS). Cancer registry follow‐up found missed cancer in five (0.22%) cases of Group B and none in Group A (NS). The sensitivity, specificity, negative and positive predictive value for cancer in Group A and B were 100%, 85.9%, 100%, 3.9% and 61.5%, 96.4%, 99.8%, 9.1%, respectively. There was increased detection of advanced adenomatous polyp (AAP) by FIT, irrespective of age, gender, and socioeconomic status (Per Protocol: odds ratio 2.69, 95% confidence interval 1.6–4.5; Intention to Screen: odds ratio 3.16, 95% confidence interval 1.8–5.4). FIT is feasible in urban, average‐risk population, which significantly improved performance for detection of AAP and CRC, despite reduced participation.     

Overall and age-specific risk advancement periods of colorectal cancer for men vs women: Implications for gender-sensitive screening offers?

Colorectal cancer (CRC) incidence and mortality are higher among men than among women. We aimed to estimate overall and age-specific risk advancement periods (RAPs) for men compared to women, which quantify how many years earlier comparable levels of risk are reached by men. RAPs were derived by Cox regression models among 331 224 participants aged 40 to 69 at baseline of the UK Biobank with no previous diagnosis of CRC and no previous CRC screening examination who were followed with respect to CRC incidence for up to 13 years. Men were at substantially higher risk of CRC than women in age groups 50 to 59 and 60 to 69, with RAPs (95% confidence intervals) as high as 8.7 (4.5-13.0) and 6.2 (4.5-7.9), respectively. These RAPs were higher than those for family history of CRC in these age groups. By contrast, no significant sex difference but a major impact of family history was seen in age group 40 to 49 (P-value for interaction between sex and age = .00079). The observed patterns suggest that consideration of gender-specific starting ages of screening might be warranted in countries in which screening offers start at ages above 50 years.     

Colorectal cancer prevention by an optimized colonoscopy protocol in routine practice

We conducted a retrospective cohort study to investigate the colorectal cancer (CRC) incidence and mortality prevention achievable in clinical practice with an optimized colonoscopy protocol targeting near‐complete polyp clearance. The protocol consisted of: (i) telephonic reinforcement of bowel preparation instructions; (ii) active inspection for polyps throughout insertion and circumferential withdrawal; and (iii) timely updating of the protocol and documentation to incorporate the latest guidelines. Of 17,312 patients provided screening colonoscopies by 59 endoscopists in South Carolina, USA from September 2001 through December 2008, 997 were excluded using accepted exclusion criteria. Data on 16,315 patients were merged with the South Carolina Central Cancer Registry and Vital Records Registry data from January 1996 to December 2009 to identify incident CRC cases and deaths, incident lung cancers and brain cancer deaths (comparison control cancers). The standardized incidence ratios (SIR) and standardized mortality ratios (SMR) relative to South Carolina and US SEER‐18 population rates were calculated. Over 78,375 person‐years of observation, 18 patients developed CRC versus 104.11 expected for an SIR of 0.17, or 83% CRC protection, the rates being 68% and 91%, respectively among the adenoma‐ and adenoma‐free subgroups (all p < 0.001). Restricting the cohort to ensure minimum 5‐year follow‐up (mean follow‐up 6.64 years) did not change the results. The CRC mortality reduction was 89% (p < 0.001; four CRC deaths vs. 35.95 expected). The lung cancer SIR was 0.96 (p = 0.67), and brain cancer SMR was 0.92 (p = 0.35). Over 80% reduction in CRC incidence and mortality is achievable in routine practice by implementing key colonoscopy principles targeting near‐complete polyp clearance.     

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.