DRAFT: Not for Citation
Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States (American Cancer Society 2008). It is estimated that 148,810 CRC cases will be diagnosed in 2008 with 49,960 deaths. The lifetime risk of being diagnosed with CRC is 5.7% for men and 5.2% for women; the lifetime risk of dying from CRC is 2.3% and 2.1% in men and women, respectively (Ries 2007). Approximately 70% of CRCs are diagnosed in persons over the age of 65; more than 90% are diagnosed over the age of 50. Only one-third of cases are detected at an early, more curable stage.
The adenoma-carcinoma sequence is considered to be the primary pathway to CRC. In the 1970s the pathologist Basil Morson conceptualized that the adenoma was the precursor lesion for CRC (Morson 1978). Screening for CRC, and its precursor lesion the adenomatous polyp, can effectively reduce CRC mortality. Randomized trials of CRC screening with a fecal occult blood test (FOBT) show a 15% to 33% reduction in CRC mortality with screening (Mandel 1993, 1999; Kronborg 1996, Hardcastle 1996) and an 18% reduction in CRC incidence (Mandel 2000). Observational studies also show that endoscopic polypectomy can markedly reduce CRC incidence and mortality (Winawer 1993, Selby 1992), and randomized controlled trials of screening with flexible sigmoidoscopy are currently in the field (Atkin 2001, Segnan 2002, Prorok 2000). Despite this demonstrated benefit of CRC screening, participation in CRC screening is only 50% in the US population aged 50 or older (Shapiro 2008).
The US Preventive Services Task Force (USPSTF) (USPSTF 2002, Pignone 2002a, USPSTF 2008), the Gastroenterology Multi-Society Task Force (Winawer 1997, 2003, 2006; Levin 2008), and the American Cancer Society (Smith 2006, Winawer 2006; Levin 2008) advocate screening for CRC for asymptomatic average-risk individuals, starting at age 50. In 2002 the USPSTF had concluded that there was insufficient information to recommend one screening strategy over another and recommended a range of screening options including FOBT, flexible sigmoidoscopy (with or without FOBT), or colonoscopy. However in November 2008 the USPSTF updated their recommendations to include stopping CRC screening at age 75 for those who had had consistent negative screenings (USPSTF 2008). They also recommended screening with a sensitive FOBT (i.e., Hemoccult SENSA or a fecal immunochemical test (FIT)), flexible sigmoidoscopy with a sensitive FOBT, or colonoscopy. Hemoccult II and flexible sigmoidoscopy alone were not recommended. The USPSTF decision was informed by microsimulation modeling from two of the Cancer Intervention and Surveillance Modeling Network (CISNET) models used for this report (Zauber 2008a).
New CRC screening tests, such as FIT, the DNA stool test, and computed tomography (CT) colonography have been introduced. In 2003 the MISCAN-Colon investigators provided a cost-effectiveness analysis of FIT to the Agency for Healthcare Research and Quality (AHRQ) for the Centers for Medicare and Medicaid Services (CMS) to inform the decision regarding whether to cover FIT and, if so, at what reimbursement fee (van Ballegooijen 2003) (http://www.cms.hhs.gov/mcd/viewtechassess.asp?where=index&id=20). In 2007, two CISNET modeling groups (MISCAN and SimCRC) conducted a similar cost-effectiveness analysis to that of FIT to estimate the threshold cost for a DNA stool test relative to currently established screening guidelines in response to a request for national coverage determination (NCD) on the use of a DNA stool test-version 1.1 (the PreGen-PlusTM test) for CRC screening among average-risk individuals every 5 years (http://www.cms.hhs.gov/mcd/viewtrackingsheet.asp?id=212). In this report three CISNET modeling groups conducted a cost-effectiveness analysis of CT colonography to estimate a threshold cost for CT colonography relative to currently recommended screening strategies in response to a National Coverage Analysis (NCA) on the use of CT colonography for CRC screening among average-risk individuals (http://www.cms.hhs.gov/mcd/viewtrackingsheet.asp?id=220).
CT colonography (also known as "virtual colonoscopy") was first described in 1994 by Vining (1994) as a CT for the colon. The key conceptual basis for CT colonography arose when it was recognized that thin-slice contiguous abdominal CT images could be reconstructed in software to simulate visualization of the lumen of the colon and create a "fly-through" display presenting polyps as prominent irregularities jutting from the colonic wall. It took a dozen years for this approach to reach the current state of technical maturity. Technological improvements have continued to refine this process. Between 2000 and 2002, commercial multi-row detector CT scanners advanced from 4-row detector devices to 8, 16 and 64-row assemblies, enabling high-speed imaging of the total abdomen within a single breath-hold, thus nearly eliminating motion artifacts that had hampered earlier efforts. Hardware and software innovations also made possible multi-planar displays and 3D dynamic simulations. A last critical contribution was the development of bowel prep procedures that optimized polyp visualization using CT colonography (Zauber 2008b).
The USPSTF recently (2008) reviewed the evidence for CT colonography as a screening test in the general population and found insufficient evidence to support recommending CT colonography for general population screening for CRC. The primary concerns were the unknown benefits and harms associated with extracolonic findings and the potential risks of radiation exposure with CT procedures. In contrast, the American Cancer Society, the Gastroenterology Multi-Society Task Force, and the American College of Radiology did include CT colonography for average-risk CRC screening in their guidelines (Levin 2008, McFarland 2008). Furthermore the ACS guidelines recommended that all individuals with lesions 6 mm or larger be referred to optical colonoscopy. The rescreening interval suggested was 5 years.
In this report we first summarize the evidence on the sensitivity and specificity of CT colonography in CRC screening. Using the best evidence for the test parameters, we then conduct simulations to determine what the reimbursement cost from CMS to providers would have to be for CT colonography in order for it to be considered comparable to other CRC screening tests from a cost-effectiveness standpoint. To accomplish this we use microsimulation modeling to project lifetime costs, life-years gained, and cost-effectiveness ratios for various CRC screening strategies (including CT colonography strategies). To add robustness to the results we use three microsimulation models, each developed independently by modelers affiliated with CISNET — a modeling consortium funded by the National Cancer Institute (NCI) that focuses on the use of modeling to improve our understanding of the impact of cancer control interventions (e.g., prevention, screening treatment) on population trends in incidence and mortality. The three simulation models, MISCAN, SimCRC, and CRC-SPIN, incorporate the best-available evidence on the natural history of colorectal disease and the screening test characteristics to project outcomes such as life-years gained compared with no screening. The results of the three models are compared; comparable results strengthen the credibility of the findings. The base-case analysis considers CT colonography every 5 years with referral of an individual with one or more lesions 6mm or larger to optical colonoscopy, using the test characteristics from the Department of Defense study (Pickhardt 2003) and the National CT Colonography Trial (NCTC) (Johnson 2008). We also assess several other scenarios as sensitivity analyses.