Postcolonoscopy colorectal cancers were more likely to arise in the proximal colon and to show microsatellite instability, according to the results of a retrospective population-based study of 168 adults with incident colorectal cancers.
In all, 64% of postcolonoscopy colorectal cancers were located in the proximal colon, compared with 44% of detected colorectal cancers (P = .016), reported Niloy Jewel Samadder, MD, of the University of Utah in Salt Lake City, together with his associates. Furthermore, microsatellite instability (MSI) was detected in 32% of postcolonoscopy colorectal cancers, versus 13% of detected colorectal cancers (P = .005). These findings may point to differences in the underlying biology of postcolonoscopy colorectal cancers and detected colorectal cancers, they said. Studies are needed “to determine if postcolonoscopy cancers arise through a specific genetic pathway that may accelerate neoplastic progression,” they wrote in Clinical Gastroenterology and Hepatology.
Postcolonoscopy colorectal cancers are a “small but clinically important subset of colorectal cancers” that are diagnosed after the patient has a colonoscopy in which no cancer is detected, the researchers noted. These cancers have an estimated global prevalence ranging from 3% to 9% and an estimated pooled prevalence of 3.7% (Am J Gastroenterol. 2014;109:1375-89). Risk factors for postcolonoscopy colorectal cancers include low adenoma detection rates, rural facilities, and care by physicians who are not gastroenterologists. However, tumor-specific and patient-specific factors, including location within the colon and superior survival, compared with detected cancers, raises the possibility of underlying molecular differences related to tumorigenesis, the researchers said.
To investigate this idea, they retrospectively analyzed data from residents of Utah between 50 and 80 years old who had a colonoscopy between, Feb. 15, 1995, and Jan. 31, 2009, at one of two large clinical facilities in Utah (Intermountain Healthcare or the University of Utah Health Sciences). Using a state population-based database, they merged medical information from these patients with cancer histories from the Utah Cancer Registry. This enabled them to compare all 84 postcolonoscopy colorectal cancers (defined as those detected within 6-60 months of colonoscopy) with tissue available for analysis with 84 detected colorectal cancers (detected within 6 months of a colonoscopy).
In the multivariable analysis, MSI was the only molecular feature that was significantly more frequent in postcolonoscopy versus detected colorectal cancers (odds ratio, 4.20; 95% confidence interval, 1.58-11.14). However, postcolonoscopy colorectal cancers were significantly more likely to be early stage (86% versus 69% for detected colorectal cancers; P = .040). Five-year survival did not significantly differ between the groups.
“The molecular signatures of postcolonoscopy colorectal cancers in our study overlap with those of sporadic MSI and serrated pathways, suggesting these mechanisms play a disproportionate role in postcolonoscopy colorectal cancers.” the researchers said. “Additional studies are needed to determine whether these postcolonoscopy colorectal cancers arise through a familial cancer pathway and/or serrated neoplastic pathway of sporadic lesions.
Funders included the American College of Gastroenterology, the National Cancer Institute, the Huntsman Cancer Foundation, the University of Utah, and the Utah Department of Health. Dr. Samadder reported consulting relationships with Cancer Prevention Pharmaceuticals and Janssen Research and Development. The other researchers reported having no conflicts of interest.
SOURCE: Samadder NJ et al. Clin Gastroenterol Hepatol. 2019 Mar 28. doi: 10.1016/j.cgh.2019.02.040.