Initial Evaluation of Rectal Bleeding in Young Persons: A Cost-Effectiveness Analysis

Colorectal cancer is the third most common cause of cancer-related death in men and women (1). The incidence increases with increasing age, and before 40 years of age, the risk for colorectal cancer is low (2). The disease can be effectively prevented by endoscopic removal of precancerous adenomatous polyps (3). After invasive cancer develops, mortality from colorectal cancer increases with advancing cancer stage at diagnosis (1). Most medical professional societies recommend routine screening with fecal occult blood testing, flexible sigmoidoscopy, colonoscopy, or barium enema beginning at 50 years of age for average-risk patients and 40 years of age for persons at increased risk (1). Rectal bleeding occurs in approximately 20% of the population annually (4-9) and most commonly results from benign anal disorders (10-14). However, when rectal bleeding is caused by a colorectal neoplasm, expedient evaluation may result in earlier detection of the neoplasm and reduced cancer-related mortality. Most studies examining the risk for colonic neoplasm in patients with rectal bleeding have been conducted predominantly in patients older than 40 years of age (10, 11, 15, 16). The probability that rectal bleeding results from a colorectal neoplasm is much lower in younger patients than in older patients. Many investigators recommend evaluation of the entire colon of older adults with rectal bleeding (10, 11, 15, 16). Rigorous evaluation of the potential risks, benefits, and costs of such a strategy in younger patients has not been reported. Thus, when faced with a young patient with rectal bleeding, clinicians must weigh the potential benefits of identifying and removing relatively rare but potentially fatal colonic neoplasms versus the potential complications and costs associated with diagnostic and therapeutic tests. We assessed the relative survival and cost-effectiveness of using alternative diagnostic strategies for young persons with otherwise asymptomatic rectal bleeding. Methods We developed a Markov analytic decision model (Figure 1) to represent the natural history of patients with rectal bleeding. The base model consisted of a 35-year-old patient presenting with otherwise asymptomatic rectal bleeding, which we defined as blood in the toilet bowl, on the tissue paper, or mixed with stool. A patient could follow one of nine strategies: no evaluation, flexible sigmoidoscopy, air-contrast barium enema, flexible sigmoidoscopy and air-contrast barium enema, colonoscopy, anoscopy followed by flexible sigmoidoscopy, anoscopy followed by air-contrast barium enema, anoscopy followed by flexible sigmoidoscopy and air-contrast barium enema, or anoscopy followed by colonoscopy. The model assumed that patients who underwent anoscopy were further evaluated by using another test only if anoscopy revealed no apparent source of bleeding (such as hemorrhoids) in the anorectal region. The model similarly assumed that patients underwent barium enema after flexible sigmoidoscopy only if sigmoidoscopy had identified no source of bleeding other than anal disease. All patients with a colonic neoplasm identified by using flexible sigmoidoscopy or barium enema were assumed to have subsequently undergone colonoscopy. Figure 1. Overview of the Markov model. Top. Bottom. Probability Estimates Table 1 summarizes the source, base-case estimates, and ranges for the probability estimates included in the model. After reviewing previous autopsy studies, Koretz (26) estimated that the prevalence of colonic neoplasms in persons 30 to 39 years of age was 0.04 for men and 0.02 for women (26). On the basis of studies of rectal bleeding in patients of all ages with colorectal cancer and polyps (30, 31, 37, 38), we estimated for our analyses that patients with rectal bleeding had a twofold increased prevalence of neoplasms. In addition, on the basis of studies of patients of all ages (9, 12, 14, 29), we assumed that patients with rectal bleeding patients and anal disease (hemorrhoids or anal fissures) identified at anoscopy were less likely than patients with rectal bleeding but without anal disease to have neoplastic lesions. In the base-case analysis, we assumed that the prevalence of neoplasms in patients with rectal bleeding and anal disease was 40% lower than that in patients with bleeding and no anal disease. Thus, in our base-case analysis, 70% of the rectal bleeding population was considered to have anal disease, and in this group, the prevalence of colonic neoplasms was estimated to be 0.036 (1.2 times that of the general population); in the 30% of the rectal bleeding population with no anal disease, the prevalence of colonic neoplasms was considered 0.06 (2.0 times that of the general population). The overall prevalence of neoplasms in persons with rectal bleeding was estimated to be 0.0432 (1.44 times that of the general population). This estimate is close to the prevalence of colonic neoplasms (0.043) reported in an endoscopic study of young persons with rectal bleeding (27). The Appendix shows the formula that we used to calculate the prevalence of neoplasms. Table 1. Probability Estimates Included in the Model Several investigators have previously estimated the time required for benign adenomas to become invasive cancer (1, 26, 42). In our model, we divided neoplasms into small adenomas (diameter < 10 mm), large adenomas, and invasive cancer. We assumed a constant annual probability that small adenomas would advance to large adenomas and that large adenomas would advance to cancer. By using the base-case estimates, we determined that approximately 9% of polyps present at the time of bleeding would progress to cancer in 10 years and that approximately 22% would progress in 20 years. Similarly, in the base case, the incidence of cancer diagnosed in the no-evaluation group was 2.1 times the expected rate for the U.S. population at 5 years and subsequently decreased toward normal (17). Cost Estimates The model used a modified societal perspective by including all direct medical costs (Table 2) regardless of who incurred the cost. Indirect costs, such as time lost from work, were not included. For the direct costs of diagnostic procedures, including physician and facility fees, we assumed that procedures were performed in an outpatient setting. We estimated the physician fees on the basis of the median fees for U.S. physicians for 2000. We based the ranges for sensitivity analyses on the maximum and minimum physician fees and based facility fees on the national average allowable charge by Medicare for 1998 (Gant G. Personal communication). In determining the cost of a surveillance colonoscopy, we assumed that 45% of patients would require polypectomy (49). We estimated the cost of caring for patients with colorectal cancer on the basis of a recent National Cancer Institutesponsored study (50) of the costs of treating patients in the Kaiser Foundation Health Plan. All costs for treating colorectal cancer were assumed to be incurred during the first year after diagnosis. The cost for pathology review of biopsy specimens and the costs for the management of perforations and bleeding after polypectomy were based on a recent cost-effectiveness model that used Medicare reimbursement rates (51). We did not include the cost of office visits for rectal bleeding or for anoscopy because we assumed that these costs would be incurred regardless of treatment strategy (the model begins after the initial office visit). We applied a 3% discount rate to costs and benefits (52). Table 2. Cost Estimates Incorporated in the Model Additional Assumptions Included in the Model In the model, we did not account for the progression of new polyps over time, although we did account for the occurrence of new polyps identified in patients undergoing cancer screening. On the basis of current understanding of the adenomacarcinoma sequence, a new polyp probably would not advance to invasive cancer more rapidly than a polyp present at the time of bleeding. Thus, the model depicted the effect of the diagnostic strategies on the natural history of the polyps and cancers present at the time of first bleeding. The model assumed that all patients with bleeding secondary to colitis would undergo colonoscopy in the first 2 years of symptoms as a result of persistent or worsening symptoms or as follow-up to flexible sigmoidoscopy or barium enema. The model assumed that without therapy, local-stage cancer would advance to regional-stage cancer within 2 years and that regional-stage cancer would advance to distant-stage cancer within 1 year. The model also assumed that all cases of advanced-stage cancer were diagnosed during the first year as a result of screening or symptoms. The model assumed that screening with flexible sigmoidoscopy would be offered every 5 years, beginning at age 50 years, but assumed that only some patients would agree to undergo screening. We assumed that surveillance colonoscopy was performed every 5 years after the diagnosis of adenomatous polyps or cancer. Quality of Life We did not assign quality-of-life estimates to the different health states in the primary model because limited data were available. However, in sensitivity analyses, we assumed that during the first 5 years after diagnosis, quality of life would decrease by 5% for patients with local or regional cancer and would decrease by 20% for patients with distant cancer. Analysis We report the results of the cost-effectiveness analyses as incremental cost-effectiveness, which we defined as the increase in cost necessary to yield a 1-year increase in survival compared with the alternative strategy. We performed one-way sensitivity analyses across the range of variables in the model and performed two-way analyses to examine the relationship of test sensitivity on the incremental cost-effectiveness ratio. We used a Monte Carlo simulation to examine the variability in the incremental cost-effectiveness rati