Long-term mortality after screening for colorectal cancer.

BACKGROUND: In randomized trials, fecal occult-blood testing reduces mortality from colorectal cancer. However, the duration of the benefit is unknown, as are the effects specific to age and sex. METHODS: In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008. RESULTS: Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction). CONCLUSIONS: The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy. (Funded by the Veterans Affairs Merit Review Award Program and others.).

Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.

BACKGROUND: In the National Polyp Study (NPS), colorectal cancer was prevented by colonoscopic removal of adenomatous polyps. We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer. METHODS: We included in this analysis all patients prospectively referred for initial colonoscopy (between 1980 and 1990) at NPS clinical centers who had polyps (adenomas and nonadenomas). The National Death Index was used to identify deaths and to determine the cause of death; follow-up time was as long as 23 years. Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population, as estimated from the Surveillance Epidemiology and End Results (SEER) Program, and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps (internal control group). RESULTS: Among 2602 patients who had adenomas removed during participation in the study, after a median of 15.8 years, 1246 patients had died from any cause and 12 had died from colorectal cancer. Given an estimated 25.4 expected deaths from colorectal cancer in the general population, the standardized incidence-based mortality ratio was 0.47 (95% confidence interval [CI], 0.26 to 0.80) with colonoscopic polypectomy, suggesting a 53% reduction in mortality. Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy (relative risk, 1.2; 95% CI, 0.1 to 10.6). CONCLUSIONS: These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer. (Funded by the National Cancer Institute and others.).

A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy.

BACKGROUND & AIMS: Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk. METHODS: We pooled individual data from 8 prospective studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance. RESULTS: During a median follow-up period of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; standard error, 2.2) and those with an adenoma 20 mm in size or greater (19.3%; standard error, 1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age (P < .0001 for trend) and male sex (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.19-1.65) were associated significantly with an increased risk for metachronous advanced neoplasia, as were the number and size of prior adenomas (P < .0001 for trend), the presence of villous features (OR, 1.28; 95% CI, 1.07-1.52), and proximal location (OR, 1.68; 95% CI, 1.43-1.98). High-grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics. CONCLUSIONS: Occurrence of advanced colorectal neoplasia is common after polypectomy. Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas.

CIMP status of interval colon cancers: another piece to the puzzle.

OBJECTIVES: Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from our group, interval cancers (colon cancers diagnosed within 5 years of a complete colonoscopy) were almost four times more likely to demonstrate microsatellite instability (MSI) than non-interval cancers. In this study we extended our molecular analysis to compare the CpG island methylator phenotype (CIMP) status of interval and non-interval colorectal cancers and investigate the relationship between the CIMP and MSI pathways in the pathogenesis of interval cancers. METHODS: We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with non-interval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for CIMP gene markers. The MSI status of subjects identified between 1989 and 2004 was known from our previous study. Tissue specimens of newly identified cases and controls (between 2005 and 2006) were tested for MSI. RESULTS: There were 1,323 cases of colon cancer diagnosed over the 17-year study period, of which 63 were identified as having interval cancer and matched to 131 subjects with non-interval cancer. Study subjects were almost all Caucasian men. CIMP was present in 57% of interval cancers compared to 33% of non-interval cancers (P=0.004). As shown previously, interval cancers were more likely than non-interval cancers to occur in the proximal colon (63% vs. 39%; P=0.002), and have MSI 29% vs. 11%, P=0.004). In multivariable logistic regression model, proximal location (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.01-3.8), MSI (OR 2.7; 95% CI 1.1-6.8) and CIMP (OR 2.41; 95% CI 1.2-4.9) were independently associated with interval cancers. CIMP was associated with interval cancers independent of MSI status. There was no difference in 5-year survival between the two groups. CONCLUSIONS: Interval cancers are more likely to arise in the proximal colon and demonstrate CIMP, which suggests there may be differences in biology between these and non-interval CRC. Additional studies are needed to determine whether interval cancers arise as a result of missed lesions or accelerated neoplastic progression.

Fecal occult blood test in patients on low-dose aspirin, warfarin, clopidogrel, or non-steroidal anti-inflammatory drugs.

AIM: To determine the effect of anticoagulants and antiplatelet medications on the positive-predictive-value of fecal occult blood test (FOBT). METHODS: All patients who underwent a colonoscopy at our institution from 1995 to 2006 for a positive FOBT were identified. Medical records were searched, and patients were stratified into five groups selected a priori: low-dose aspirin, NSAIDs, warfarin, clopidogrel, or controls. The positive-predictive-value of FOBT for advanced colonic neoplasia was computed for each group. RESULTS: During the study period, 1,126 patients underwent colonoscopy for a positive FOBT and met entry criteria. The average age of study participants was 69 years and most were men. The positive-predictive-value of FOBT for advanced colon neoplasia was significantly higher in the control group (30.5%) when compared to those on low-dose aspirin (20.5%; p = 0.003), NSAIDs (19.7%; p = 0.003), clopidogrel (7.3%; p = 0.002), or warfarin (20%; p = 0.05). The positive-predictive-value of FOBT was significantly lower for those on clopidogrel than those on low-dose aspirin (p = 0.04) and NSAIDs (p = 0.05), but not warfarin (p = 0.08). The positive-predictive-value for FOBT was similar for those on aspirin, NSAIDs, and warfarin. There was a linear trend between the number of number of positive FOBT cards and prevalence of advanced colon neoplasia (p = 0.01). CONCLUSION: Anticoagulants and antiplatelet medications lower the positive-predictive-value of FOBT for advance colonic neoplasia and should be stopped if clinically feasible prior to stool collection.

Is BRAF mutation associated with interval colorectal cancers?

INTRODUCTION: Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to rapid tumor growth. The aim of this study was to compare the association of BRAF V600E mutation in interval versus non-interval colorectal cancers and to determine the relationship between BRAF mutation and 5-year survival. METHODS: We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched to patients with non-interval cancers. Archived cancer specimens were tested for BRAF V600E mutation and MSI. RESULTS: There were 63 interval and 131 non-interval cancers. BRAF mutation was present in 28% of interval cancers compared to 19% of non-interval cancers (P = 0.18). In a multivariable logistic regression model, proximal location (OR 1.85; 95% CI 1.01-3.8) and MSI (OR 2.7; 95% 1.1-6.8) were independently associated with interval cancers while BRAF mutation was not (OR 0.93; 95% CI 0.36-2.38). BRAF mutation portended a poor 5-year survival, particularly among microsatellite stable cancers. CONCLUSIONS: BRAF mutation is not associated with interval cancers but is a marker of poor prognosis, particularly in microsatellite stable cancers.

Variation in detection of adenomas and polyps by colonoscopy and change over time with a performance improvement program.

BACKGROUND & AIMS: There has been no prospective, community-based study to track changes in adenoma detection by individual physicians over time and to determine the effectiveness of targeted educational interventions. METHODS: We prospectively collected information on 47,253 screening colonoscopies in average-risk individuals 50 years and older performed by a community-based practice in the Twin Cities of Minnesota. During a period of 3 years, 5 specific interventions were implemented; each was designed to improve adenoma detection rates. Controlling for patient-related and procedure-related factors, rates of adenoma detection and 3-year trends for individual physicians were plotted, and intraclass correlation coefficients were calculated. Generalized estimating equations were used to identify factors associated with detection of adenomas and polyps. RESULTS: At least 1 polyp and 1 adenoma were found in 36% and 22% of examinations, respectively. Adenoma detection rates by endoscopists ranged from 10%-39%. There was no significant improvement during the study period despite planned, systematic interventions. Factors associated with adenoma detection included age of the patient (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.02), male sex (OR, 1.53; 95% CI, 1.34-1.74), and adequate preparation quality (OR, 2.26; 95% CI, 1.64-3.12). CONCLUSIONS: The detection of adenomas by individual physicians during a 3-year period varied and did not appear to change between individual endoscopists, despite planned, systematic interventions. This indicates that other targeted interventions might be required to improve adenoma detection rates among experienced, community gastroenterologists.

Validation of a questionnaire to assess self-reported colorectal cancer screening status using face-to-face administration.

PURPOSE: The aim of this study was to assess the accuracy of a National Cancer Institute (NCI)-developed colorectal cancer screening questionnaire. METHODS: We conducted 36 cognitive interviews and made iterative changes to the questionnaire to improve comprehension. The revised questionnaire was administered face-to-face to 201 participants. The primary outcome was agreement between questionnaire responses and medical records for whether or not a participant was up-to-date for any colorectal cancer screening test. RESULTS: Comprehension of descriptions and questions was generally good; however, the barium enema description required several revisions. The sensitivity of the questionnaire for up-to-date screening status was 94%, specificity 63%, and concordance 88%. CONCLUSIONS: The modified questionnaire was highly sensitive for determining if a person was up-to-date for any colorectal cancer screening test, although the specificity was low. Given the difficulty of obtaining all relevant records, self-report using this questionnaire is a reasonable option for identifying people who have undergone testing.

A randomized trial of aspirin to prevent colorectal adenomas.

BACKGROUND: Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel. METHODS: We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals. RESULTS: Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 percent). The incidence of one or more adenomas was 47 percent in the placebo group, 38 percent in the group given 81 mg of aspirin per day, and 45 percent in the group given 325 mg of aspirin per day (global P=0.04). Unadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg group (95 percent confidence interval, 0.69 to 0.96) and 0.96 in the 325-mg group (95 percent confidence interval, 0.81 to 1.13). For advanced neoplasms (adenomas measuring at least 1 cm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the respective relative risks were 0.59 (95 percent confidence interval, 0.38 to 0.92) and 0.83 (95 percent confidence interval, 0.55 to 1.23). CONCLUSIONS: Low-dose aspirin has a moderate chemopreventive effect on adenomas in the large bowel.

Folic acid for the prevention of colorectal adenomas: a randomized clinical trial.

CONTEXT: Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine. OBJECTIVE: To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma. INTERVENTION: Participants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later). MAIN OUTCOME MEASURES: The primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (> or =25% villous features, high-grade dysplasia, size > or =1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or > or =3 adenomas). RESULTS: During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. CONCLUSIONS: Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00272324.

Colorectal cancer screening: the potential role of virtual colonoscopy.

Virtual colonoscopy is a promising new technique that combines rapid spiral CT scanning of the abdomen with advanced computer programs capable of re-creating two- and three-dimensional views of the colon and rectum. Recent studies comparing this method with conventional colonoscopy show that virtual colonoscopy already is more accurate than barium enema X-ray studies for the detection of colorectal polyps, and that it approaches the accuracy of colonoscopy for diagnosing advanced lesions. Before virtual colonoscopy can be promoted for population-based screening for colorectal cancer, a number of issues discussed in this review need to be addressed. These include questions of accuracy, availability, acceptability, and cost-effectiveness.

Fecal occult blood test screening for colorectal cancer.

In summary, high-quality scientific studies indicate that the use of the FOBT for colorectal cancer screening has a number of important advantages. The test is capable of detecting most early colorectal cancers and many advanced adenomas. It has been shown in randomized, controlled trials to reduce substantially colorectal cancer mortality and incidence. The FOBT is feasible, widely available, and acceptable to most individuals. It has a low up-front cost and is highly cost-effective. Combining annual FOBT with periodic flexible sigmoidoscopy seems to be an especially effective screening option. Limitations of FOBT screening include its low sensitivity for polyps, especially smaller ones. Some of the trials report a relatively low sensitivity for detecting cancers located in the distal colon. The test has a relatively low specificity, so there are many false-positive screens; and for it to be most effective, repetitive screening is necessary. Balancing these advantages and disadvantages, the evidence-based screening guidelines have concluded that FOBT screening has a major role to play in colorectal cancer control and a program of annual FOBT plus flexible sigmoidoscopy every 5 years is a preferred option for screening the asymptomatic, average-risk population for colorectal cancer. Short of doing direct colonoscopy screening for the entire at-risk population, the FOBT currently is the best available method of identifying asymptomatic, average-risk people most likely to benefit from colonoscopy.

Effectiveness and cost-effectiveness of colorectal cancer screening: Selecting the ideal strategy.

Colorectal cancer is the second most common cancer killer of Americans. Recently developed and tested methods of screening and surveillance can effectively diagnose and treat the disease in most patients before symptoms develop when the chance of cure is high. It is also possible to prevent colorectal cancer by detecting and resecting premalignant adenomatous polyps. Evidence-based guidelines recommend that the average-risk population greater than age 50 be screened with annual faecal occult blood tests plus periodic flexible sigmoidoscopy. This approach is feasible, efficacious, affordable and cost-effective in a high-risk country such as the US. Widespread compliance with these recommendations could reduce the mortality from this malignancy by more than 50%.

Should the quality of preparation impact postcolonoscopy follow-up recommendations?

A high-quality bowel cleansing preparation is an essential prerequisite for a safe, efficient, and accurate colonoscopy. Large studies, however, have shown that up to 25% of patients undergoing colonoscopy have what is considered to be an inadequate preparation. A well-done survey reported in this issue of the American Journal of Gastroenterology by Ben-Horin et al. found considerable variability among endoscopists in their assessment of preparation adequacy from photographs of three representative cases. When the preparation was judged suboptimal, follow-up colonoscopy often was recommended at shorter time intervals than is currently indicated by clinical guidelines. Because this practice is not supported by any direct investigation, a better practice might be to determine if the preparation is poor or inadequate, indicating instead the need for a prompt repeat preparation and another colonoscopy.

Should patients with anemia and low normal or normal serum ferritin undergo colonoscopy?

BACKGROUND: Patients with unexplained iron deficiency anemia have a greater prevalence of colonic neoplasia, and should be evaluated for a colonoscopy. The approach to patients with anemia without iron deficiency remains unclear. OBJECTIVE: To compare the prevalence of colonic neoplasia in anemic patients with normal ferritin (>50 ng/mL), to those with ferritin < or =50 ng/mL, and nonanemic individuals. METHODS: Patients referred for colonoscopy for anemia evaluation were stratified into 3 groups: ferritin < or =50 ng/mL, 51-100 ng/mL, and >100 ng/mL. We compared these groups to each other, and to asymptomatic nonanemic individuals undergoing screening colonoscopy. The prevalence of advanced colonic neoplasia was determined for each group using existing records. RESULTS: During the study period, 414 patients who underwent colonoscopy for anemia evaluation and 323 nonanemic individuals who underwent colonoscopy for cancer screening met inclusion criteria. Study subjects were mostly men. The prevalence of advanced colonic neoplasia in subjects with ferritin 51-100 ng/mL was 7.2% (95% CI 2.4-17.9%), similar to 7.9% (95% CI 5.1-11.9%) in those with ferritin < or =50 ng/mL. The incidence of advanced colonic neoplasia in subjects with ferritin >100 ng/mL was 1.7% (95% CI 0.1-6.6%), similar to 1.2% (95% CI 0.4-3.3%) in the asymptomatic nonanemic group. After adjusting for age, patients with ferritin < or =50 ng/mL and 51-100 ng/mL were almost 5 times more likely to harbor advanced colonic neoplasia than the other groups. The addition of other laboratory parameters did not improve the predictive value of ferritin. CONCLUSION: A ferritin cutoff of 100 ng/mL can be used to determine the need for colonoscopy in men with anemia.

Evaluating follow-up of positive fecal occult blood test results: lessons learned.

The objective of this study was to assess the effectiveness of a follow-up system for positive fecal occult blood test (FOBT) results in a single tertiary care hospital. The system consisted of a designated nurse who reviewed records of all positive FOBT cases for appropriate follow-up testing and notified clinic managers if no follow-up occurred. This system identified 63/423 (15%) of positive FOBT cases with inadequate follow-up in a 10-month period, but it was unsuccessful in ensuring subsequent follow-up in 24% of these cases. Primary care providers often lacked knowledge regarding appropriate follow-up testing. More direct follow-up of positive FOBT results is recommended.

Colorectal cancer screening education, prioritization, and self-perceived preparedness among primary care residents: data from a national survey.

BACKGROUND: Colorectal cancer (CRC) screening remains underutilized in the United States. We conducted a national survey of CRC screening education, prioritization, and self-perceived preparedness among resident physicians in Family Practice (FP), Internal Medicine (IM), and Obstetrics and Gynecology (OB/GYN) training programs. METHODS: Directors/administrators from 1085 FP, IM, and OB/GYN training programs were contacted by e-mail with a request to forward an invitation to participate in our Web-based CRC screening education survey to all residents in their program. Willing residents submitted responses in anonymous fashion. Data were analyzed using chi2 tests and analysis of variance methods. RESULTS: In total, 243 program directors/administrators forwarded our invitation, and 835 residents responded (384 FP, 266 IM, 177 OB/GYN, 8 undesignated specialty). Nearly all resident responders (89%) had received CRC screening education, but few content delivery methods were reported. Most felt at least somewhat comfortable or somewhat knowledgeable with respect to advising patients about CRC screening (90%), currently endorsed CRC screening guidelines (89%), and criteria used to identify familial CRC syndromes (50%). However, substantially fewer respondents reported feeling very comfortable or very knowledgeable in these areas (45%, 23%, and 5%, respectively). Program specialty, level of training, and gender were the strongest indicators of self-perceived preparedness. CONCLUSIONS: Although based on a relatively small sample of all FP, IM, and OB/GYN residents, these data suggest tangible opportunities to improve the CRC screening curriculum in primary care residency programs.

Five-year colon surveillance after screening colonoscopy.

BACKGROUND & AIMS: Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain. We conducted a prospective study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy. METHODS: Three thousand one hundred twenty-one asymptomatic subjects, age 50 to 75 years, had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs. One thousand one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years. Cohorts were defined by baseline findings. Relative risks for advanced neoplasia within 5.5 years were calculated. Advanced neoplasia was defined as tubular adenoma greater than > or =10 mm, adenoma with villous histology, adenoma with high-grade dysplasia, or invasive cancer. RESULTS: Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia. The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83-4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10-11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74-14.94) with tubular adenoma > or =10 mm, 6.05 (95% CI: 2.48-14.71) for villous adenoma, and 6.87 (95% CI: 2.61-18.07) for adenoma with high-grade dysplasia. CONCLUSIONS: There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance. Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia.