118 Optimizing Implementation of Fecal Immunochemical Testing in Organized Colorectal Cancer Screening: A Randomized Controlled Trial

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had a colonoscopy (C1) for a positive gFOBT (Hemoccult II) between September 2003 and December 2005 within the CRC screening program implemented in the Haut-Rhin, a French administrative area. All C1 displaying polyp(s) or cancer (C1aN) and a sample of 300 negative C1 (C1N) were included. The time interval observed between C1 and C2 was compared with that recommended by the French guidelines established in 2004 (+/- 6 months). Results: Main outcomes are presented in the table. 1203 subjects were included (mean age 62.9 years, 58.9% men, 991 C1aN and 212 C1N) and followed up for a median of 8.4 years (range 1.1 - 9.8). The same gastroenterologist performed C1 and C2 procedures in 79.7% of cases. The rate of correct surveillance varied from 20% to 62.5% depending on the gastroenterologist, that of oversurveillance from 0% to 46.7% and that of undersurveillance from 10.7% to 80.0%. The cumulative probability of a C2 within 5 years was 87.8% in the CRC group, 62.6% in the high-risk adenoma group (advanced adenoma or ≥3 adenomas), 28.5% in the low-risk adenoma group and 5.0% in the no adenoma group (63.3%, 29.0%, 6.8% and 1.3% within 3 years, respectively). The probability of not undergoing a C2 within 8 years was 7.2%, 22.6%, 43.0% and 87.1% in the same groups, respectively. 225 (24.9%) subjects with a neoplasia detected at C1 had no surveillance colonoscopy. This rate was significantly higher in subjects aged 65-74 (31.4%) than in younger people (20.1%) (p<0.001) without difference relating to sex. An intercurrent disease justified undersurveillance in 25 cases only (5.3%). The rate of anticipated C2 was 24.6% in 126 people with inadequate bowel preparation, not significantly different of that observed in 1077 people with adequate preparation (20.2%, p=0.2). Conclusion: In our organized CRC FOBT screening program, misuse of surveillance colonoscopy is the rule rather than the exception, underuse being more frequent than overuse. This has to be taken into account when assessing the harms of screening. The screening centers in charge of the program should organize followup invitations to improve adherence to surveillance recommendations.

AGA Abstracts

Impact on Colorectal Cancer Mortality of Screening Programmes Based on Immunochemical Fecal Occult Blood Test in the Veneto Region (Italy) Manuel Zorzi, Ugo Fedeli, Elena Schievano, Emanuela Bovo, Stefano Guzzinati, Carla Cogo, Chiara Fedato, Mario Saugo, Angelo Paolo Dei Tos, Fabio Monica Background There is evidence that colorectal cancer (CRC) screening programmes based on guaiac fecal occult blood test reduce CRC-specific mortality. Several studies showed higher performances of fecal immunochemical test (FIT) compared to guaiac test. In Italy most CRC screening programmes utilize FIT, but data on their impact on mortality are lacking. Methods In the Veneto Region (north-east of Italy), FIT screening programmes were activated in different areas between 2002 and 2009. Subjects 50-69 years old are invited every two years to perform FIT and, if positive, are referred to colonoscopy. We compared CRC mortality between areas where screening was activated in 2002-2004 (early screening areas - ESA) and in 2008-2009 (late screening areas - LSA). For ESA and LSA we computed CRC mortality rates of 50-74 years old subjects in 2002-2011 and the Annual Percent Change (APC), with 95% Confidence intervals (CI95%). The association between mortality time trends and screening activation was evaluated by a Poisson regression model with an interaction term between year and area, adjusting for age and gender. To evaluate whether changes in mortality reflected different underlying incidence rates, we analyzed CRC incidence from 1995 to 2006 (last year available) of the two areas included in the Veneto Cancer Registry. Results The mid-period 50-74yrs resident population of ESA and LSA was respectively 288,125 and 357,486. In the study period CRC mortality rates in ESA declined from 45.7 per 100,000 in 2002 to 36.2 in 2011. In LSA mortality was stable around 45 per 100,000 (FIgure 1).The APC was -3.5% (CI95% -5.3% to -1.6%) in ESA and -0.5% (CI95% -2.5% to 1.5%) in LSA. Poisson regression showed a significant interaction between area and year, with a 2.8% (p=0.029) reduction of mortality rates attributable to screening per year. The estimated reduction of CRC mortality in ESA vs LSA was 25% over the whole study period. However, the association between area and mortality rates was observed only in females (6.2% annual reduction, p=0.004) but not in males. The incidence rates in LSA progressively increased between 1995 and 2006, with a APC of +1.4% (CI95% 0.8% to 2.0%) over the whole period. The ESA showed an increase between 2000 and 2003 (APC +9.9%; CI95% 5.9% to 14.1%) followed by a steep reduction (APC -22.4%; CI95% -35.1% to -7.4%)(Figure 2). Conclusion The ESA showed a 25% reduction of CRC mortality compared to the LSA, independent from underlying incidence rates. This ecological study represents one of the first evidences of the impact on mortality of FIT screening programmes. Further research on this topic is needed.

117 "Real World" Experience With CT Colonography Brent Lacey, Brian D. Tran, Theodore Schafer

Figure 1.Standardized(Veneto population 2007)CRC mortality rates,by year and period of activation of screening programmes.50-74yrs old subjects

Introduction CT colonography (CTC) and colonoscopy detect medium and large polyps with comparable efficacy in clinical trials. However, these pivotal studies were performed in academic centers with tightly regimented protocols. The goal of CTC is adenoma detection, but studies have not evaluated whether CTC subsequently leads to adenoma resection in routine clinical practice. When evaluating the utility of CTC, it is also critical to consider the time and cost necessary to evaluate extracolonic findings. The purpose of our study was to evaluate the use and cost-effectiveness of CTC in a community-based medical center. Methods We retrospectively reviewed 421 consecutive CTC studies performed for colorectal cancer screening at a community-based tertiary referral hospital from Jan. 1-Dec. 31, 2010. We analyzed reasons for referral, study limitations, resultant colonoscopies, and the time and cost associated with evaluating extracolonic findings discovered during CTC. Results After accounting for patient preference and risk for sedation, 12% of patients were not appropriate candidates for CTC. 154 (37%) studies had at least one factor limiting CTC interpretation, such as poor bowel preparation or motion artifact. 33 patients had regional limitations confined to the distal colon, within reach of a flexible sigmoidoscope. 24 patients with intracolonic findings on CTC did not undergo follow-up colonoscopy. 80 patients underwent colonoscopy following CTC, and 2 patients underwent surgery. 32 (7.6% of all CTC studies evaluated) patients had either adenomas or adenocarcinomas resected, including 6 advanced adenomas and 2 adenocarcinomas. 24 extracolonic findings of high clinical significance were encountered, including 9 aneurysms of major arteries and 13 solid masses. The masses included an ovarian cystic teratoma and a renal cell carcinoma. 72 (17%) patients had extracolonic findings requiring additional outpatient workup with an average per-patient cost of $816.97, above the $361.44 cost of the CTC. The median time to resolution of extracolonic findings was 105 days, with a maximum of 730 days. Patients had an average of 2.5 follow up appointments for these issues over a 2 year period prior to resolution. Conclusion CTC performed well in the closed environment of a clinical trial. However, in clinical practice, effectiveness of CTC is often hampered by factors that limit interpretation, most of which can be overcome by colonoscopy. In this cohort, CTC led to adenoma resection two-thirds less often than colonoscopy, primarily due to factors limiting interpretation of CTC and failure to undergo colonoscopy for intracolonic findings. The cost of evaluating extracolonic findings more than triples the cost of CTC. CTC may rarely encounter extracolonic findings of high clinical importance, offering an additional benefit not provided by colonoscopy.

Figure 2.Standardized(European Population 2001)CRC incidence rates,by year and period of activation of screening programmes.50-74yrs old subjects

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Optimizing Implementation of Fecal Immunochemical Testing in Organized Colorectal Cancer Screening: A Randomized Controlled Trial Jill M. Tinmouth, Linda Rabeneck, Nancy N. Baxter, Lawrence Paszat, Edward Randell, Rinku Sutradhar, Mardie Serenity

Surveillance Colonoscopies in an Organized Colorectal Cancer Screening Program With Guaiac Fecal Occult Blood Test: A Population-Based Cohort Study Bernard Denis, Isabelle Gendre, Philippe Perrin

Introduction Fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening improves detection of CRC and advanced adenomas compared to guaiac fecal occult blood testing (gFOBT). However, FIT is reported to be unstable over time and at extreme temperatures. Prior to implementation in Ontario's CRC screening program, a pilot study of FIT was conducted. Aim The aim of the study was to inform the implementation of FIT in Ontario, particularly, to determine the impact on participation rates of (1) different methods of FIT distribution and (2) different methods of FIT return. Methods This was a block factorial randomized controlled trial. Participants comprised all patients eligible for screening enrolled with 28 Ontario family physicians. Interventions included 2 distribution methods (direct mail-out of FIT vs. mailed invitation to pick-up FIT at family doctor's office) and 2

In clinical practice, surveillance colonoscopy is often overused among low-risk subjects and underused among high-risk subjects. It has never been assessed in the setting of an organized colorectal cancer (CRC) screening program. Aim: To assess use of surveillance colonoscopy in the French population-based CRC screening program using guaiac fecal occult blood test (gFOBT). Methods: Retrospective review of the surveillance colonoscopies (C2) performed by 34 community gastroenterologists in a cohort of average risk residents aged 50-74 having

AGA Abstracts

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return methods (FIT returned via regular mail vs. drop-off at a laboratory service centre). One sample quantitative FIT kits (either NS-Plus Chemistry analyzer, Alfresa Pharma Corp., Japan or OC-Sensor DIANA IFOB Test System, Eiken Chemical Company Ltd., Japan) were used. The primary outcome was return of a completed one sample FIT kit. Patients with positive results (≥75 ng hgb/mL) were recommended colonoscopy. The primary outcome was compared by distribution method, return method and kit type using multivariate regression to adjust for patient, physician factors and kit type. Results Of the 3780 patients in our cohort, 685 (18%) returned a completed FIT kit. Of the 1839 that were mailed a kit, 436 (24%) returned it compared to 249 (13%) of the 1941 who were asked to visit their family physician to pick up a kit. Rates of return were similar in those who were asked to drop off a kit (330 of 1890 (18%)) and those who were asked to mail it back (344 of 1818 (19%)). After adjustment for kit type as well as patient and physician factors, FIT kit return was significantly associated with distribution method (single mail out vs. pick up: O.R. 2.97, 95% C.I. 2.04 - 4.32, p < 0.0001 and repeat mail out vs. pick up: O.R. 2.75, 95% C.I. 2.27 - 3.33, p < 0.0001) but not with method of return. 13.6% of participants had result of 75ng hgb/mL or greater while 10.9% had a result of 100 ng hgb/mL or higher. Positivity rates declined with increasing time from stool collection to testing. Conclusions Improved participation rates were associated with directly mailing the FIT kit but not with method of return. Our findings are of considerable interest to decision-makers in jurisdictions where FIT is being considered or is used in organized CRC screening.

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BACKGROUND: The fecal immunochemical test (FIT) is currently the Kaiser Permanente Northern California (KPNC) outreach program's colorectal cancer (CRC) screening test of choice. FIT performance over multiple rounds of annual testing in the same population is unknown. We therefore assessed FIT positivity rates, positive predictive values, and CRC sensitivity over four rounds of annual testing. METHODS: FIT performance was measured in a KPNC cohort of 179,423 asymptomatic, average-risk patients who completed an initial FIT in either 2007 or 2008 and were followed over 3 subsequent annual rounds of testing. Eligible members were 50-70 years of age on their initial FIT mailing date, had a FIT result within 365 days of the initial mail date, and had no record of a prior sigmoidoscopy within 5 years or colonoscopy within 10 years. Tests were analyzed using an OC-Sensor Diana (Polymedco Inc) using a cutoff level of 100 ng Hgb/mL buffer. RESULTS: Individuals who completed testing within 1 year of their FIT mail date averaged 58.5±5.7 years, 53.5% were female, and 60.1% were white. FIT positivity rates (4.3% overall) were highest in the initial year at 5.2% and lower in subsequent years (3.6%-3.8%). Adenoma and CRC positive predictive values were also highest in the first year of testing (34.3% and 3.3%, respectively). Positivity rates and adenoma positive predictive values were higher in men and older patients. A total of 773 CRCs were diagnosed over four rounds; 664 (85.9%) were FIT screened in the year before diagnosis. Of those 664 FIT-screened, 545 CRCs (82.1%) were FIT detected and 119 (17.9%) were FIT-missed. CRC sensitivity was highest in year 1 at 85.5% and lower in subsequent rounds (80.9%, 78.8%, and 73.6%), although confidence intervals overlapped. CRC sensitivity did not vary significantly by sex, age, CRC location, or stage at diagnosis. About two-thirds of CRCs were found in the distal colon, regardless of whether they were FIT detected, missed, or unscreened. Finally, FIT-detected CRCs were more frequently diagnosed at an early stage compared to FIT-missed or unscreened CRCs (72.5% vs. 63.0%; p=0.037 and 72.5% vs. 58.7%; p<0.004). CONCLUSIONS: In this large community-based setting, among those FIT screened in the prior year, 73.6% to 85.5% of CRCs diagnosed were FIT detected. Positivity rates, positive predictive values, and CRC sensitivity were highest in the first year of testing, likely due to higher rates of prevalent disease. FIT positivity rates and adenoma positive predictive values were also higher in men and older individuals. Finally, the finding that FIT-detected CRCs were more frequently diagnosed at an early stage underscores the effectiveness of an annual FIT screening program in reducing the burden of CRC. Table 1. Participation and FIT Positivity

119 Impact of Adjusting for Patient Demographics on Physician Adenoma Detection Rates in a Large, Community-Based Setting Christopher D. Jensen, Theodore R. Levin, Chyke A. Doubeni, Virginia P. Quinn, Joanne E. Schottinger, Ann G. Zauber, Amy R. Marks, Wei Zhao, Nirupa R. Ghai, Jennifer L. Schneider, Bruce H. Fireman, Charles Quesenberry, Douglas A. Corley Background: Adenoma detection rate (ADR) - the percentage of a physician's screening colonoscopy exams in which a colorectal adenoma or cancer is found - has emerged as a performance quality metric and predicts subsequent colorectal cancer risk following a screening exam. Reliable physician ADR estimates are needed to inform colonoscopy quality standards, yet minimal data exist on the contributions of patient demographics to variation in ADRs between physicians. Methods: We evaluated the ADRs of endoscopists who performed 108,662 total and 20,792 screening colonoscopy exams between 2006-2008, among Kaiser Permanente Northern California health plan members ≥50 years of age. We then evaluated the impact of adjusting for patient age, sex, race/ethnicity, and family history of colorectal cancer on ADR variability and the relative rank order of physician ADRs. Results: Among 102 physicians, 68 (67%) had crude ADRs that met existing gastroenterology society guidelines for screening exams of ≥25% for male patients and 69 (68%) met the threshold of ≥15% for female patients, although rates varied widely (males: 7.7%-61.5%; females: 1.7%-45.6%). Adjustment of physician ADRs for patient demographics substantially decreased ADR variability (from 8-fold to 3-fold in males; from 27-fold to 5-fold in females). Adjustment changed the rank order for some physicians (largest increase was 11 ranks; largest decrease was 14 ranks); however, few changed quartiles of ADR (e.g., adjustment moved 3 physicians out of (and 3 into) the lowest ADR quartile). Physician ADRs were highly correlated for male and female patients (r=0.71, P<0.001) and ADRs (for screening exams) also predicted adenoma detection rates for non-screening exams (screening vs. non-screening; r=0.84 males and r=0.87 females, P<0.001). Conclusions: A large majority of community-based endoscopists exceed the ADR thresholds recommended by gastroenterology society guidelines; however, substantial ADR variability exists, similar to that reported in academic and referral settings. A portion of this variability is due to differences in patient demographics. The accuracy of ADRs as a quality metric for some physicians may be enhanced by adjusting for patient demographics beyond patient sex (e.g., age, race/ethnicity, and family history), although few physicians changed quartiles of ADR. The primary utility of adjustment will depend upon how ADRs are used. For tracking quality improvement, unadjusted rates may suffice for identifying quartiles of performance and changes in physicians' ADRs over time. However, if ADRs are used as the basis for rewarding or penalizing individual providers, accurate determination of ADRs may require accounting for differences in patient demographics between physicians. Impact of Adjusting for Patient Characteristics on Ranking of Physician Adenoma Detection Rate

CI = confidence interval Table 2. Adenoma and CRC Positive Predictive Value (PPV) and CRC Sensitivity

*Change in rank order with adjustment for patient age, race/ethnicity, and family history of colorectal cancer compared to ranking based on crude physician adenoma detection rate.

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AGA Abstracts

AGA Abstracts

Fecal Immunochemical Test Performance Over Multiple Rounds of Annual Testing in an Outreach Screening Program Pauline A. Mysliwiec, Christopher D. Jensen, Wei Zhao, Carrie Klabunde, Jeffrey K. Lee, Douglas A. Corley, Theodore R. Levin