Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease

Abstract

Background: Patients with longstanding ulcerative colitis and colonic Crohn's disease have an increased risk of colorectal cancer compared with the general population. This review assesses the evidence that endoscopic surveillance may prolong life by allowing earlier detection of colon cancer or its pre-cursor lesion, dysplasia in patients with inflammatory bowel disease.

Objectives: To assess the effectiveness of cancer surveillance programs in reducing the death rate from colorectal cancer in patients with ulcerative colitis and colonic Crohn's disease.

Search strategy: The following strategies were used to identify relevant studies: 1. MEDLINE and the Cochrane Central Register of Controlled Trials were searched from 1966 to December 2002. The medical subject headings "Ulcerative Colitis", "Crohn Disease" or "Inflammatory Bowel Disease" and "Surveillance" or "Cancer" were used to perform key-word searches of the databases. 2. Hand searching of reference lists from papers.

Selection criteria: Potentially relevant articles were reviewed independently and unblinded by three authors to determine if they fulfilled the selection criteria. Each article was rated as being eligible, ineligible, or without sufficient information to determine eligibility. Any disagreement between reviewers was resolved by consensus. Any trials published in abstract form were only considered if it was possible to obtain full details of the protocol and results from the authors.

Data collection and analysis: Eligible articles were reviewed in duplicate and the results of the primary research trials were abstracted onto specially designed data extraction forms. The proportion of patients dying from bowel cancer or other causes in the control and surveillance groups of each study was derived from life tables, survival curves or where possible, by calculating life tables from the data provided. Data from the original research articles were converted into 2x2 tables (survival versus death x surveillance versus control) for each of the individual studies for comparable follow-up intervals. The presence of significant heterogeneity among studies was tested by the chi-square test. Because this is a relatively insensitive test, a p value of less than 0.1 was considered statistically significant. Provided statistical heterogeneity was not present (p>0.10), the fixed effects model was used for the pooling of data. The 2x2 tables were combined into a summary test statistic using the pooled relative risk (RR) and 95% confidence intervals as described by Cochrane and Mantel and Haenszel.

Main results: Karlen 1998a found that 2/40 of the patients dying of colorectal cancer had undergone surveillance colonoscopy on at least one occasion compared with 18/102 of the controls (RR 0.28, 95% confidence interval 0.07 to 1.17). One of 40 patients who died from colorectal cancer had undergone surveillance colonoscopies on two or more occasions compared with 12/102 controls (RR 0.22, 95% confidence interval 0.03 to 1.74) in contrast to a more modest effect observed for patients who had only one colonoscopy (RR 0.43, 95% confidence intervals 0.05 to 3.76). Choi 1993 found that carcinoma was detected at a significantly earlier stage in the surveillance group; 15/19 had Duke's A or B carcinoma in the surveilled group compared to 9/22 in the non-surveilled group (P= 0.039). The 5-year survival rate was 77.2% for cancers occurring in the surveillance group and 36.3% for the no-surveillance group (P= 0.026). Four of 19 patients in the surveillance group died from colorectal cancer compared to 11 of 22 patients in the non-surveillance group (RR 0.42, 95% CI 0.16 to 1.11). Lashner 1990 found that four of 91 patients in the surveillance group died from colorectal cancer compared to 2 of 95 patients in the non-surveilled group (RR 2.09, 95% CI 0.39 to 11.12). Colectomy was less common in the surveillance group, 33 compared to 51 (p < 0.05) and was performed four years later (after 10 years of disease) in the surveillance group. For the pooled data analysis 8/110 patients in the surveillance group died from colorectal cancer compared to 13/117 patients in the non-surveillance group (RR 0.81, 95% CI 0.17 to 3.83).

Reviewers' conclusions: There is no clear evidence that surveillance colonoscopy prolongs survival in patients with extensive colitis. There is evidence that cancers tend to be detected at an earlier stage in patients who are undergoing surveillance and these patients have a correspondingly better prognosis but lead-time bias could contribute substantially to this apparent benefit. There is indirect evidence that surveillance is likely to be effective at reducing the risk of death from IBD-associated colorectal cancer and indirect evidence that it is acceptably cost-effective.