Colonoscopy and Colorectal Cancer Mortality in the Veterans Affairs Health Care System

Colonoscopy is the dominant method for colorectal cancer (CRC) screening in the United States (1). It was first endorsed for this indication in 1997 on the basis of several observational studies and the concept that it would extend the benefits of sigmoidoscopic screening to the entire colon. Screening colonoscopy became a Medicare benefit in 2001, and its use has increased exponentially, with estimates of overall annual colonoscopy volume ranging from 11.5 to 14 million (2, 3). However, screening colonoscopy is not supported by randomized controlled trials, and recent studies have questioned whether it offers incremental benefit over sigmoidoscopy in the proximal colon. Casecontrol studies in Canadian populations showed that colonoscopy was associated with reduced risk for death from left-sided but not right-sided CRC (4, 5). Conversely, studies from Germany (68) and the United States (9) reported that colonoscopy was associated with decreased incidence and mortality for both left-sided and right-sided CRC, although the benefit was less in the proximal colon. These inconsistent findings and variable degrees of protection against CRC have been partly attributed to operator-dependent quality factors (10). The Veterans Health Administration (VHA) is the largest integrated health care provider in the United States. The VHA system includes 170 medical centers and 1063 outpatient clinics, which serve nearly 9 million enrolled veterans each year. Use of colonoscopy for CRC screening in the VHA has been expanding; a more than 2-fold increase in use of screening colonoscopy and a decrease in use of sigmoidoscopy and double-contrast barium enema were noted between 1997 and 2003 (11), and the VHA endorsed colonoscopy as a primary CRC screening option for patients aged 50 years or older in 2007. Despite these trends, it is unknown whether colonoscopy decreases CRC mortality among veterans and whether the effect varies on the basis of anatomical location of CRC. Estimating colonoscopy effectiveness is important from an individual perspective. Veterans differ from the general population with regard to risk factors for colon neoplasia (male sex and cigarette smoking) and have higher CRC and adenoma prevalence (12). From a systems perspective, the VHA is centralized and is less reliant on financial incentives for individual providers and may therefore provide a reference standard for other health care systems. In the context of increasing use of colonoscopy and its dominance as a CRC screening method in the United States, knowledge of its effect on important patient outcomes is critical to guide health care resource use and policy, both within the VHA and in other health care settings. We conducted a casecontrol study using national Veterans Affairs (VA)Centers for Medicare and Medicaid Services (CMS) administrative data to determine whether colonoscopy is associated with decreased CRC mortality in veterans and whether its effect differs by anatomical location of CRC. Methods The study was approved by the Institutional Review Boards at Indiana UniversityPurdue University Indianapolis and Dartmouth Institute Dartmouth-Hitchcock Medical Center and by the Research and Development Committees of the Richard L. Roudebush VA Medical Center in Indianapolis, Indiana, and the VA Medical Center in White River Junction, Vermont. Study Population The sampling frame comprised veterans with inpatient and/or outpatient visits at any VA facility from 1997 to 2010. Definitions of case patients and control patients are broadly similar to those used in previous studies by Baxter and colleagues (4, 9). To ensure that patients were representative of veterans who receive care predominantly in the VHA system (13), we included only veterans with at least 2 primary care visits at 1 VA facility in the 3 years before CRC diagnosis in case patients and before the corresponding index date in control patients. Identification of Case Patients Case patients were veterans who received a diagnosis of CRC when they were aged 50 years or older and died of CRC when they were aged 52 years or older. Case patients were identified from 1 January 2002 to 31 December 2008 and died of CRC between 1 January 2002 and 31 December 2010. Patients with a diagnosis of CRC who died of other causes were not counted as case patients. Patients with a history of CRC or surgical resection of CRC before 1 January 2002 were excluded, as were those with Crohn disease, ulcerative colitis, or familial polyposis. Cancer was categorized as right-sided (cecum, ascending colon, hepatic flexure, or transverse colon) or left-sided (splenic flexure, descending colon, sigmoid colon, or rectum). Identification of Control Patients Control patients were assigned an index date that corresponded to the date of CRC diagnosis in their matched case patient. Control patients were veterans who were not diagnosed with CRC before the index date and did not die of the disease before 31 December 2010. For each case patient, we matched 4 control patients according to age (1 year), sex, and VA medical center. Similar to case patients, control patients with a history of Crohn disease, ulcerative colitis, or familial polyposis were excluded. As in prior studies, control patients were alive at the time of death of a matched case patient (4, 9). Exposure The exposure was defined as receipt of colonoscopy between 1 January 1997 and 6 months before CRC diagnosis in case patients or the corresponding index date in control patients (Figure). If a case patient had undergone more than 1 colonoscopy during the exposure period, the first one was counted as the exposure. We performed subgroup analysis to determine exposure to screening colonoscopy, using an algorithm developed and validated in VA administrative data by El-Serag and colleagues (11) for classification of colonoscopy indication according to administrative codes. The algorithm defines screening colonoscopy on the basis of the absence of prior codes associated with gastrointestinal disorders (diagnostic indication) or a history of polyps (surveillance indication). The algorithm has sensitivity of about 70% and specificity of about 72%. Figure. Study design. CRC= colorectal cancer. Confounding Factors For all patients, we calculated a Charlson Comorbidity Index score (14, 15) based on 1 inpatient code or 2 or more outpatient codes separated by at least 30 days within the year before the index date (date of diagnosis for case patients and corresponding date for control patients) (16). We measured duration of use, expressed as the number of days of aspirin, nonsteroidal anti-inflammatory drug (NSAID), and statin prescription. This was categorized as none, up to 3 years, 3 to 5 years, and more than 5 years. We adjusted for confounders that may affect CRC risk, including race; Charlson Comorbidity Index score; socioeconomic status; diabetes mellitus; cigarette smoking; family history of CRC; ischemic heart disease; cholecystectomy; and use of aspirin, NSAIDs, and statins. We measured the number of prostate-specific antigen measurements in men during the study period to assess propensity for health care use. Data Sources VA Central Cancer Registry (VACCR) The VACCR was used to ascertain CRC diagnoses for case patients and exclusion of CRC among control patients. Cancer diagnoses within the VHA are submitted to the registry every 6 months. The VACCR includes demographic information, date of diagnosis, pathologic confirmation, cancer location within the colon and rectum, previous cancer, and stage of cancer. The registry has excellent sensitivity (17). VA Medical SAS Data Sets These data sets contain national administrative data on all VA inpatient stays and outpatient encounters. The data were used to abstract patient-level information on performance and dates of colonoscopy, comorbidities, and primary care visits. Outpatient procedures are coded using Current Procedural Terminology and Healthcare Common Procedure Coding System codes. Inpatient procedures and diagnoses are coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Linked VACMS Data These data were used to identify veterans who had colonoscopies in non-VA facilities for which CMS was the primary payer. Similar to the VA medical SAS data sets, the VACMS data contain inpatient and outpatient data, including diagnoses, procedure dates, and other information on health care use. Department of Defense Suicide Data Registry This registry was used to identify patients with CRC who died of their disease (case patients). The registry contains information on date and cause of death for all VA health system users, based on information from the National Death Index, which is the gold standard for death ascertainment. At the time of the study, information on cause of death was available through 2010. VA Pharmacy Benefits Management (PBM) Services The PBM, which contains information on all outpatient prescriptions dispensed within the VHA since fiscal year 1999, was accessed to obtain information on exposure to aspirin, other NSAIDs, and statins from 1999 to the day before the index date. Statistical Analysis Descriptive statistics for demographic and clinical variables were calculated for all patients. We used the chi-square test or the Fisher exact test to compare proportions and the t test to compare continuous variables. The primary analysis was based on the matched quintuplets (1 case patient and 4 control patients). We performed conditional logistic regression with adjustment for potential confounders to calculate odds ratios (ORs) and 95% CIs for death from CRC by exposure to colonoscopy. This calculation was done using colonoscopy as the exposure and was then repeated with screening colonoscopy as the exposure (based on El-Serag and colleagues' algorithm [11]). To investigate the association between exposure to colonoscopy and anatomical location of CRC (right- o