Reduce Colorectal Cancer Mortality Research Articles

Design of a randomized controlled trial to assess the comparative effectiveness of a multifaceted intervention to improve adherence to colorectal cancer screening among patients cared for in a community health center

BackgroundColorectal cancer (CRC) is common and leads to significant morbidity and mortality. Although screening with fecal occult blood testing (FOBT) or endoscopy has been shown to decrease CRC mortality, screening rates remain suboptimal. Screening rates are particularly low for people with low incomes and members of underrepresented minority groups. FOBT should be done annually to detect CRC early and to reduce CRC mortality, but this often does not occur. This paper describes the design of a multifaceted intervention to increase long-term adherence to FOBT among poor, predominantly Latino patients, and the design of a randomized controlled trial (RCT) to test the efficacy of this intervention compared to usual care.MethodsIn this RCT, patients who are due for repeat FOBT are identified in the electronic health record (EHR) and randomized to receive either usual care or a multifaceted intervention. The usual care group includes multiple point-of-care interventions (e.g., standing orders, EHR reminders), performance measurement, and financial incentives to improve CRC screening rates. The intervention augments usual care through mailed CRC screening test kits, low literacy patient education materials, automated phone and text message reminders, in-person follow up calls from a CRC Screening Coordinator, and communication of results to patients along with a reminder card highlighting when the patient is next due for screening. The primary outcome is completion of FOBT within 6 months of becoming due.DiscussionThe main goal of the study is to determine the comparative effectiveness of the intervention compared to usual care. Additionally, we want to assess whether or not it is possible to achieve high rates of adherence to CRC screening with annual FOBT, which is necessary for reducing CRC mortality. The intervention relies on technology that is increasingly widespread and declining in cost, including EHR systems, automated phone and text messaging, and FOBTs for CRC screening. We took this approach to ensure generalizability and allow us to rapidly disseminate the intervention through networks of community health centers (CHCs) if the RCT shows the intervention to be superior to usual care.Trial registrationClinicalTrials.gov NCT01453894

219 Incidence and Phenotype At Diagnosis of Inflammatory Bowel Disease Across 9 Countries in Asia-Pacific

Whether the results of randomized controlled trials on colorectal cancer (CRC) screening with guaiac fecal occult blood test (gFOBT) are transposable in the real world is questionable. gFOBT has several drawbacks, one is the requirement for frequent testing, which may limit compliance and thereby effectiveness. Aim: To assess the short term outcomes of the four first rounds of a population-based CRC screening program using gFOBT. Methods: Comparison of the outcomes of the four first rounds (R1 to R4) of the organized CRC screening program with Hemoccult II implemented in the Haut-Rhin, a French administrative area, since 2003 (Denis B et al Gut 2007;56:1579-84). All average-risk residents aged 50 74 were invited by mail to participate every other year. Results: Main outcomes are presented in the table. The crude uptake rate decreased from 47.9% to 38.5%. The decrease in adjusted uptake was similar in men and women but was observed in younger age groups (50 64) only and maximal in the 50 54 year age group. 15.8% of people who participated in Rn did not participate in Rn+1. Overall, 56.7% of the target population had completed at least one test and 19.6% four tests. More than 80% of the completed tests were provided by general practitioners. The positive predictive value for advanced neoplasia decreased significantly from 31.4% in R1 to 26.1% in R4 (and detection rate from 9.7‰ to 4.7‰). The rate of stage I colon cancers decreased significantly from 44.9% in R1 to 38.1% in R4. Conclusion: Participation and yield deteriorated with time in our organized population-based gFOBT CRC screening program. This deterioration was not observed in previous randomized controlled trials on gFOBT screening and may question the reproducibility of their effectiveness on the reduction of CRC mortality in the real world. Effort is needed to enhance uptake and to reduce inequalities in participation related to sex, age, place of residence and deprivation.

218 Results From the First Four Rounds of the Colorectal Cancer Screening Program With Guaiac Fecal Occult Blood Test Conducted in the Haut-Rhin (Alsace, France)

Whether the results of randomized controlled trials on colorectal cancer (CRC) screening with guaiac fecal occult blood test (gFOBT) are transposable in the real world is questionable. gFOBT has several drawbacks, one is the requirement for frequent testing, which may limit compliance and thereby effectiveness. Aim: To assess the short term outcomes of the four first rounds of a population-based CRC screening program using gFOBT. Methods: Comparison of the outcomes of the four first rounds (R1 to R4) of the organized CRC screening program with Hemoccult II implemented in the Haut-Rhin, a French administrative area, since 2003 (Denis B et al Gut 2007;56:1579-84). All average-risk residents aged 50 74 were invited by mail to participate every other year. Results: Main outcomes are presented in the table. The crude uptake rate decreased from 47.9% to 38.5%. The decrease in adjusted uptake was similar in men and women but was observed in younger age groups (50 64) only and maximal in the 50 54 year age group. 15.8% of people who participated in Rn did not participate in Rn+1. Overall, 56.7% of the target population had completed at least one test and 19.6% four tests. More than 80% of the completed tests were provided by general practitioners. The positive predictive value for advanced neoplasia decreased significantly from 31.4% in R1 to 26.1% in R4 (and detection rate from 9.7‰ to 4.7‰). The rate of stage I colon cancers decreased significantly from 44.9% in R1 to 38.1% in R4. Conclusion: Participation and yield deteriorated with time in our organized population-based gFOBT CRC screening program. This deterioration was not observed in previous randomized controlled trials on gFOBT screening and may question the reproducibility of their effectiveness on the reduction of CRC mortality in the real world. Effort is needed to enhance uptake and to reduce inequalities in participation related to sex, age, place of residence and deprivation.

Colonoscopy and colorectal cancer mortality: both sides of the story

Colonoscopy and colorectal cancer mortality: both sides of the story

Shift to earlier stage at diagnosis as a consequence of the National Bowel Cancer Screening Program

To assess the impact of the National Bowel Cancer Screening Program (NBCSP) in South Australia. A cohort comparison of colorectal cancer (CRC) patient data from the NBCSP register and the South Australian Cancer Registry. Patient records of those invited to take part in screening through the NBCSP, those who participated in the program, and those with positive test results were compared with those of the rest of the study population (excluding the group of interest) on an intention-to-screen basis. Stage of CRC at diagnosis as a surrogate marker for effect on CRC mortality. Of 3481eligible patients, 221had been invited to the NBCSP. Invitees were more likely to have stage A lesions compared with all other patients (34.8% versus 19.2%; P<0.001), and half as likely to have stage D CRC (5.4% versus 12.4%; P <0.001). A further shift towards earlier stage was seen in those who participated in screening and those with positive test results compared with all other patients (38.8% stage A and 3.0% stage D in screening participants versus 19.3% stage A and 12.4% stage D in all other patients; and 39.7% stage A and 2.6% stage D in those with positive test results versus 19.3% stage A and 12.4% stage D in all other patients; P <0.001). CRCs were diagnosed at a significantly earlier stage in people invited to the NBCSP compared with those who were not invited, regardless of participation status or test result. The NBCSP should lead to reductions in CRC mortality in Australia.

Critical considerations of fecal occult blood tests for colorectal cancer

1University of Dundee, Nethergate, Dundee, DD1 4HN, Scotland, UK *Author for correspondence: r.j.c.steele@dundee.ac.uk The most commonly used strategy in colo­ rectal cancer (CRC) screening pro grams involves the use of stool tests to detect occult blood, and guaiac fecal occult blood tests (gFOBTs) are, to date, the only fecal tests shown to reduce CRC mortality in population­based randomized trials [1]. However, gFOBTs also carry disadvantages. A major concern is that interval cancers account for around 50% of cancers detected in gFOBT screened populations [2] and recent data show that gFOBTs are less sensitive in women than in men, and in both rectal and right­sided cancers when compared with left­sided disease [2,3]. In addition, the test is associated with a high false­positive rate with no neoplasia detected in around half of colonoscopies performed following a positive gFOBT [2,3]. This may be, in part, explained by the fact that gFOBTs are not specific for human hemoglobin (Hb) and are subject to possible dietary interference from, for example, red meat and high­peroxidase fruits and vegetables. As a result, it has been common practice to instruct participants to adhere to dietary restrictions ahead of sample collection, although this may act as a barrier to screening and affect participation rates [4]. However, data from a meta­analysis did not support dietary restrictions with gFOBTs, leading to recommendations that restrictions are abandoned to improve adherence rates [5]. Fecal immunochemical tests (FITs) are now available and are increasingly being used in screening programs. Unlike gFOBTs, FITs are specific for the detection of human Hb, eliminating any potential for dietary interference, and are also more specific than gFOBT for lower gastrointestinal bleeding. In addition, modern FITs generally allow a more convenient method of sample collection, and are associated with better participation rates [6]. Another major advantage of FIT is that automated versions not only eliminate interobserver variability, but also the quantitative nature of these tests allow provision of a measured fecal Hb concentration. Screening program “...the adoption of fecal immunochemical tests in colorectal cancer screening programs has potential to address participation, appropriate positivity rates and the problem of false‐negative results.” EDITORIAL

Increasing colorectal cancer screening adherence: comment on "A randomized comparison of print and web communication on colorectal cancer screening".

Increasing colorectal cancer screening adherence: comment on "A randomized comparison of print and web communication on colorectal cancer screening".

The price of autonomy: should we offer individuals a choice of colorectal cancer screening strategies?

A difference between colorectal cancer screening and screening for most other types of cancer is that various screening methods are available. A choice between screening methods is common in the USA. Most European programmes currently offer a single screening method, since it is recommended that only screening strategies with sufficient evidence for a reduction in colorectal cancer mortality are introduced. Faecal occult blood testing is widely accepted in Europe, and evidence on the effectiveness of flexible sigmoidoscopy is increasing. The availability of multiple effective screening options warrants deliberation on whether individuals should be given a choice between strategies. In this Personal View, we present arguments in favour and against offering a choice of screening strategies, together with the evidence substantiating these views. We also focus on screening invitees' autonomy, which is a crucial parameter in the debate.

Fundamental Causes of Colorectal Cancer Mortality in the United States: Understanding the Importance of Socioeconomic Status in Creating Inequality in Mortality

We used the fundamental cause hypothesis as a framework for understanding the creation of health disparities in colorectal cancer mortality in the United States from 1968 to 2005. We used negative binomial regression to analyze trends in county-level gender-, race-, and age-adjusted colorectal cancer mortality rates among individuals aged 35 years or older. Prior to 1980, there was a stable gradient in colorectal cancer mortality, with people living in counties of higher socioeconomic status (SES) being at greater risk than people living in lower SES counties. Beginning in 1980, this gradient began to narrow and then reversed as people living in higher SES counties experienced greater reductions in colorectal cancer mortality than those in lower SES counties. Our findings support the fundamental cause hypothesis: once knowledge about prevention and treatment of colorectal cancer became available, social and economic resources became increasingly important in influencing mortality rates.

The Association between NSAID Use and Colorectal Cancer Mortality: Results from the Women's Health Initiative

Randomized trial evidence shows that nonsteroidal anti-inflammatory drug (NSAID) use, particularly long-term use, reduces the incidence of colorectal neoplasia. Recent data also suggests an inverse association between NSAID use and death due to colorectal cancer (CRC). We examined the association between NSAID use and CRC mortality among 160,143 postmenopausal women enrolled in the Women's Health Initiative. Women provided details on medication use at baseline and three years after enrollment. Reported CRC cases were locally confirmed and centrally adjudicated; cause of death was determined according to centralized medical record and death certificate review. Cox regression was used to investigate the association between NSAID use and CRC mortality. Overall, NSAID use at baseline was not associated with CRC mortality [HR: 0.93; 95% confidence interval (CI) 0.76, 1.14]. However, women who reported NSAID use at both baseline and year 3 experienced reductions in CRC mortality (HR: 0.72; 95% CI 0.54, 0.95) compared with nonusers. Results suggest that NSAID use is associated with lower CRC mortality among postmenopausal women who use these medications more consistently over time. impact: Our results support prolonged NSAID use in postmenopausal women for the prevention of poor CRC outcomes.

The impact of population-based faecal occult blood test screening on colorectal cancer mortality: a matched cohort study

Background:Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme.Methods:Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000–2007) before the roll out of a national programme. All residents (50–69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier.Results:There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83–0.99) overall and 0.73 (95% CI 0.65–0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06–1.38).Conclusion:There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants.

Proximal Fluid Proteome Profiling of Mouse Colon Tumors Reveals Biomarkers for Early Diagnosis of Human Colorectal Cancer

Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for the early diagnosis of CRC. Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins. The FabplCre;Apc(15lox/+) mouse model represents early-stage development of human sporadic CRC. Proximal fluids were collected from normal colon and colon tumors and subjected to in-depth proteome profiling by tandem mass spectrometry. Carcinoembryonic antigen (CEA) and CHI3L1 human serum protein levels were determined by ELISA. Of the 2,172 proteins identified, quantitative comparison revealed 192 proteins that were significantly (P < 0.05) and abundantly (>5-fold) more excreted by tumors than by controls. Further selection for biomarkers with highest specificity and sensitivity yielded 52 candidates, including S100A9, MCM4, and four other proteins that have been proposed as candidate biomarkers for human CRC screening or surveillance, supporting the validity of our approach. For CHI3L1, we verified that protein levels were significantly increased in sera from patients with adenomas and advanced adenomas compared with control individuals, in contrast to the CRC biomarker CEA. These data show that proximal fluid proteome profiling with a mouse tumor model is a powerful approach to identify candidate biomarkers for early diagnosis of human cancer, exemplified by increased CHI3L1 protein levels in sera from patients with CRC precursor lesions.

351 Adherence to Screening in a Randomized Controlled Trial of a One-Time Screening Colonoscopy Versus Program of Annual Fecal Occult Blood Test (gFOBt): Implications of Lower gFOBt Adherence to Screening on Colorectal Cancer Mortality Reduction

351 Adherence to Screening in a Randomized Controlled Trial of a One-Time Screening Colonoscopy Versus Program of Annual Fecal Occult Blood Test (gFOBt): Implications of Lower gFOBt Adherence to Screening on Colorectal Cancer Mortality Reduction

Su1876 Proximal Fluid Proteome Profiling of Mouse Colon Tumors Reveals Biomarkers for Early Diagnosis of Human Colorectal Cancer

Purpose: Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for the early diagnosis of CRC. Experimental Design: Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins. The FabplCre;Apc 15lox/þ mouse model represents early-stage development of human sporadicCRC. Proximalfluids werecollected fromnormalcolon andcolontumors and subjected to in-depth proteome profiling by tandem mass spectrometry. Carcinoembryonic antigen (CEA) and CHI3L1 human serum protein levels were determined by ELISA. Results: Of the 2,172 proteins identified, quantitative comparison revealed 192 proteins that were significantly (P 5-fold) more excreted by tumors than by controls. Further selection for biomarkers with highest specificity and sensitivity yielded 52 candidates, including S100A9, MCM4,andfourotherproteinsthathavebeenproposedascandidatebiomarkersforhumanCRCscreening or surveillance, supporting the validity of our approach. For CHI3L1, we verified that protein levels were significantlyincreasedinserafrompatientswithadenomasandadvancedadenomascomparedwithcontrol individuals, in contrast to the CRC biomarker CEA. Conclusion: These data show that proximal fluid proteome profiling with a mouse tumor model is a powerful approach to identify candidate biomarkers for early diagnosis of human cancer, exemplified by increased CHI3L1 protein levels in sera from patients with CRC precursor lesions. Clin Cancer Res; 18(9); 2613-24. � 2012 AACR.

Abstract 622: Estrogen plus progesterone and colorectal cancer incidence and mortality in the Women's Health Initiative

Abstract Background: During the intervention period in the Women's Health Initiative (WHI) trial, estrogen plus progestin use was associated with lower colorectal cancer incidence but the cancers were diagnosed at substantially higher stage. To assess the long term influence of estrogen plus progestin on this disease, analyses were conducted over the entire follow-up period. Methods: The WHI study is a randomized, double-blind, placebo-controlled, clinical trial involving 16,608 postmenopausal women aged 50-79 years with an intact uterus who were randomly assigned to a once-daily tablet of 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (N=8,506) or matching placebo (N=8,102). We assessed incidence, tumor characteristics, and mortality rates for invasive colorectal cancers. Analyses were by intention to treat. The study is registered with clinical trials CT.gov NCT00000611. Findings: After a mean of 5.6 years (SD 1.03) of therapy and 11.6 (SD 3.1) years of total follow-up, 118 women in the combined hormone therapy group were diagnosed with colorectal cancer vs 145 in the placebo group (incidence/year 0.12% vs 0.16%; hazard ratio [HR] 0.72, 95% confidence interval (CI), 0.56-0.94; P=0.014). Bowel screening exams were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (53.4% vs 30%, P=0.007) and were at higher stage (regional or distant, 68.8% vs 51.4%, P=0.003). Somewhat more women died from colorectal cancer in the combined hormone therapy group (37 vs 27 deaths; 0.04% vs 0.03%; HR 1.29, 95% CI 0.78-2.11, P=0.320). Interpretation: Although estrogen plus progestin use was associated with lower colorectal cancer incidence, the cancers were at more advanced stage and no trend for colorectal cancer mortality reduction emerged. These findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 622. doi:1538-7445.AM2012-622

Adherence to Colorectal Cancer Screening

Despite evidence that several colorectal cancer (CRC) screening strategies can reduce CRC mortality, screening rates remain low. This study aimed to determine whether the approach by which screening is recommended influences adherence. We used a cluster randomization design with clinic time block as the unit of randomization. Persons at average risk for development of CRC in a racially/ethnically diverse urban setting were randomized to receive recommendation for screening by fecal occult blood testing (FOBT), colonoscopy, or their choice of FOBT or colonoscopy. The primary outcome was completion of CRC screening within 12 months after enrollment, defined as performance of colonoscopy, or 3 FOBT cards plus colonoscopy for any positive FOBT result. Secondary analyses evaluated sociodemographic factors associated with completion of screening. A total of 997 participants were enrolled; 58% completed the CRC screening strategy they were assigned or chose. However, participants who were recommended colonoscopy completed screening at a significantly lower rate (38%) than participants who were recommended FOBT (67%) (P<.001) or given a choice between FOBT or colonoscopy (69%) (P<.001). Latinos and Asians (primarily Chinese) completed screening more often than African Americans. Moreover, nonwhite participants adhered more often to FOBT, while white participants adhered more often to colonoscopy. The common practice of universally recommending colonoscopy may reduce adherence to CRC screening, especially among racial/ethnic minorities. Significant variation in overall and strategy-specific adherence exists between racial/ethnic groups; however, this may be a proxy for health beliefs and/or language. These results suggest that patient preferences should be considered when making CRC screening recommendations. Trial Registration clinicaltrials.gov Identifier: NCT00705731.

Application of Autofluorescence Endoscopy for Colorectal Cancer Screening: Rationale and an Update

As the result of basic researches, several intravital fluorophores have been determined so far in human colorectal tissue. Autofluorescence endoscopy (AFE) can detect slight alterations in their distribution and concentration during the colorectal carcinogenesis process and, thus facilitate noninvasive screening colonoscopies without the need for fluorescent substances or staining reagents to be administered. While detecting faint autofluorescence intensity by conventional fiberoptic endoscopy remains challenging, the latest AFE system with high-resolution videoendoscope capabilities enables such detection by using a false-color display algorithm. To this end, the diagnostic benefits of AFE have been reported in several multicenter randomized controlled studies of colorectal cancer (CRC) screening and differential diagnosis. CRC screening using the latest AFE technology could, therefore, lead to future reductions in CRC mortality.

Screening Based on Risk for Colorectal Cancer Is the Most Cost-Effective Approach

Performing single endoscopic examinations or selective screening based on risk might be more practical than recommended screening strategies for colorectal cancer (CRC). We investigated the cost effectiveness of these strategies, under real-life conditions of suboptimal compliance, and the societal cost perspective. We used Markov modeling to analyze data from 787,000 individuals in Singapore, aged 50 to 75 years, with an age-standardized rate of CRC of 30 to 40/100,000 in 2009. Potential outcomes, incremental cost-effectiveness ratio, and net health benefit were compared between single sigmoidoscopy or colonoscopy and current recommended screening strategies, and also with a strategy of selective screening based on risk of CRC. Performing single sigmoidoscopies on individuals when they are 60 years old was the cheapest screening strategy; it would reduce CRC incidence by 19% and mortality by 16%, compared with no screening. A single colonoscopy is less cost effective than a single sigmoidoscopy, unless the proportion of right-sided lesions exceeds 65%. The fecal occult blood test (iFOBT) had the lowest incremental cost-effectiveness ratio when all strategies were compared with no screening; iFOBT and colonoscopic examinations every 10 years each had extended dominance over other strategies. Screening subjects 50 to 60 years old by iFOBT and subjects 60 to 72 years old with colonoscopies every 10 years was the most cost-effective strategy (US$25,000/quality-adjusted life-years). Risk for CRC, adherence, and cost of colonoscopy were the main determinants of cost effectiveness, based on sensitivity analysis. Markov modeling analysis indicates that selectively screening individuals for CRC based on risk is the most cost-effective approach; it limits the cost and number of colonoscopies needed and significantly reduces CRC mortality.

Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up

BackgroundThree large randomised trials have shown that screening for colorectal cancer (CRC) using the faecal occult blood test (FOBt) can reduce the mortality from this disease. The largest of these...

Abstract A69: The association between NSAID use and colorectal cancer mortality: Results from the Women's Health Initiative

Abstract Introduction: Observational and experimental evidence demonstrate that non-steroidal anti-inflammatory drug (NSAID) use reduces the incidence and recurrence of colorectal neoplasia. Consistent with such observations, recent studies have also suggested an inverse association between NSAID use, particularly long-term use, and colorectal cancer (CRC) mortality. We examined the association between aspirin and non-aspirin NSAID use and colorectal mortality among post-menopausal women enrolled in the clinical trial and observational study arms of the Women's Health Initiative (WHI). Methods: We investigated the effect of NSAID use on colorectal cancer mortality among 160,143 women enrolled in the WHI with available follow up data who did not report a prior history of colorectal cancer at the time of study entry. Women provided details on aspirin and non-aspirin NSAID use at both study baseline and three years after enrollment. Reported cases of colorectal cancers were locally confirmed based on medical records and also centrally adjudicated. Cause of death was determined according to centralized medical record and death certificate review; routine linkages were made to National Death Index files to ensure the completeness of vital status information. There were 2,119 confirmed cases of colorectal cancer and 492 deaths among WHI participants where the listed cause of death was colorectal cancer. Cox proportional hazards regression was used to examine the relationship between NSAID use (at study baseline and at year 3 of study follow-up) and colorectal cancer mortality and to estimate hazard ratios and 95% confidence intervals. We conducted a sensitivity analysis that excluded women who developed colorectal cancer within the first three years following study enrollment (n=180) in order to restrict the study question to examining the role of NSAID use prior to diagnosis on colorectal cancer mortality. Results: Reported use of NSAIDs at study baseline, including aspirin, ibuprofen, and prescription NSAIDs, was not associated with colorectal cancer mortality (HR: 0.93; 95% CI 0.76–1.14). However, among women who lived to year 3 after study enrollment (n=156,440; 98% of participants), those who reported use of NSAIDs at both baseline and year 3 experienced reductions in colorectal cancer mortality of approximately 30% (HR: 0.72; 95% CI 0.54–0.95) compared to women who did not report use at both time points. Results from the sensitivity analysis demonstrated that prolonged pre-diagnostic NSAID use (use at both baseline and year 3) was significantly associated with reduced colorectal cancer mortality (HR: 0.70; 95% CI 0.52–0.93). Conclusion: Our results suggest that use of NSAIDs is associated with lower colorectal cancer mortality among post-menopausal women, particularly in women who use these medications for longer periods of time prior to diagnosis. This association may reflect an effect of NSAID use in decreasing the incidence of new tumors and/or an effect in lowering rates of disease progression. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A69.