Prevalence and predictors of interval colorectal cancers - what hypotheses should colonoscopists consider in planning studies to modify the undesirable outcome.

Title: Prevalence and predictors of interval colorectal cancers in Medicare beneficiaries

Authors: Cooper GS, Xu F, Barnholtz Sloan JS, Schluchter MD, Koroukian SM

Journal: Cancer 2011 Oct 11. doi: 10.1002/cncr.26602. [Epub ahead of print]

Summary

A recent report on prevalence and predictors of interval colorectal cancers in Medicare beneficiaries was published in Cancer. The study was prompted by historical data that after a colonoscopy that is negative for cancer, a subset of patients may be diagnosed with colorectal cancer termed interval cancer. The frequency and predictors have not been well studied in a population-based US cohort. The authors used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 57,839 patients aged ≥69 years who were diagnosed with colorectal cancer between 1994 and 2005 and who underwent colonoscopy within 6 months of cancer diagnosis. Colonoscopy performed between 6 and 36 months before cancer diagnosis was a proxy for interval cancer. The results showed that by using the case definition, 7.2% of patients developed interval cancers. Factors that were associated with interval cancers included proximal tumor location (distal colon: multivariable odds ratio [OR], 0.42; 95% confidence interval [CI], 0.390-0.46; rectum: OR, 0.47; 95% CI, 0.42-0.53), increased co-morbidity (OR, 1.89; 95% CI, 1.68 2.14 for ≥3 co-morbidities), a previous diagnosis of diverticulosis (OR, 6.00; 95% CI, 5.57-6.46), and prior polypectomy (OR, 1.74; 95% CI, 1.62-1.87). Risk factors at the endoscopist level included a lower polypectomy rate (OR, 0.70; 95% CI, 0.63-0.78 for the highest quartile), higher colonoscopy volume (OR, 1.27; 95% CI, 1.13-1.43), and specialty other than gastroenterology (colorectal surgery: OR, 1.45; 95% CI, 1.16-1.83; general surgery: OR, 1.42; 95% CI, 1.24-1.62; internal medicine: OR, 1.38; 95% CI, 1.17-1.63; family practice: OR, 1.16; 95% CI, 1.00-1.35). The authors concluded that a significant proportion of patients developed interval colorectal cancer, particularly in the proximal colon. Contributing factors likely included both procedural and biologic factors, emphasizing the importance of meticulous examination of the mucosa.

Opinion

In addressing approaches within the control of the colonoscopists to overcome the problem of interval cancers [1], points well-referenced in a recent editorial [2] bear repeating. A new water method with water exchange [3,4] has emerged with randomized controlled trial (RCT) data showing an impact on both colonoscopy pain [5] and adenoma detection rate (ADR) [6]. Practical steps to ensure success include complete air exclusion and water exchange in a collapsed lumen (Table 1).

Table 1

The water method with water exchange (adapted from references 2 and 3)

Retrospective data hinted that poor bowel preparation limited adenoma detection. Data in prospective RCT, however, do not substantiate the speculation that better bowel cleanliness scores increase ADR. Split-dose preparation improved bowel cleanliness assessed by unbiased observers, but no comparative information on ADR was presented. Although bowel preparation scores (Ottawa scale) could be improved by morning preparation for afternoon colonoscopy, the improved cleanliness did not alter overall detection rate of polyps, adenomatous polyps or number of patients with adenomas. In the right colon one split-dose study showed 2 L polyethylene glycol (PEG) + ascorbic acid provided a signifi cantly better bowel preparation score than PEG + bisacodyl but not a significantly higher ADR. Parenthetically another split-dose study of similar regimen reproduced the superior cleansing effect but showed no increase in polyp/malignancy detection rate. Furthermore the best bowel cleanliness score was not associated with the highest odds of finding polyps in a study reporting better bowel preparation quality scores being associated with greater odds of polyp detection. The effects of other modern approaches in modifying polyp detection rate or ADR also have been conflicting. These include use of high-definition, wide-angle endoscope, dye-spray chromoendoscopy, and withdrawal time >6 min. Narrow band imaging did not enhance ADR. Monitoring and feedback could increase polyp detection but whether such measures will translate into increase in ADR, or if the observations can be reproduced by others is unknown. The third eye retroscope consistently increased total number of adenomas detected in the proximal colon in unblinded studies, but the impact on ADR was not described.

With regard to the explanation of the impact of the water method with water exchange on enhancing ADR, the following hypotheses deserve further testing. After appropriate water exchange the need for suction during the withdrawal phase to remove residual feces is reduced. This minimizes collapse/ contraction of the colon and the need for re-insufflation of air to maintain a distended lumen for inspection. The withdrawal phase is not interrupted by “distractions” allowing the colonoscopist to concentrate on inspection for lesions. The increased proportion of time devoted to inspection during withdrawal of the endoscope may be the critical factor.

The performance of screening colonoscopy in the proximal colon is imperfect. The water method with water exchange developed to minimize discomfort during insertion may have yielded a serendipitous benefit of enhancing ADR. Whether the enhanced detection may provide a timely solution to the problem of missed lesions and ameliorate the problem of interval cancers in the proximal colon is unknown. A multicenter RCT enrolling large numbers of subjects should be supported.