Interval colorectal cancers were proximally located and had DNA mismatch repair deficiency significantly more often than did colorectal cancers in colonoscopy-naive patients, researchers reported in the November issue of Gastroenterology.
The findings underscore the need to effectively visualize the large colon to avoid missing lesions during colonoscopy, said Elena M. Stoffel, MD, MPH, of the University of Michigan Health System, Ann Arbor, and her associates. “Studies consistently show that colonoscopy affords less protection against proximal cancers, and DNA mismatch repair deficiency tumors are more frequent among proximal cancers,” they noted. But the proximal and distal colon also have different embryologic origins and gene expression profiles, “prompting some to suggest that these might be considered as two distinct organs. Whether the precursors of postcolonoscopy colorectal cancers are simply harder to detect or resect endoscopically, or whether their behavior differs on the basis of anatomic location or molecular subtype remains unclear,” they added.
Courtesy Wikimedia Commons/nephron/Creative Commons License
Tumor budding in colorectal carcinoma is shown here.
A variety of quality-related factors contribute to the risk of postcolonoscopy or interval colorectal cancer, as do clinical characteristics such as older age at diagnosis, proximal tumor location, family history of colorectal cancer, and previous polypectomy, the investigators noted. To further explore the clinical and molecular correlates of postcolonoscopy tumors, they conducted a cross-sectional study of 10,365 colorectal cancers diagnosed in Denmark between 2007 and 2011 (Gastroenterology. 2016 Jul 18. doi: 10.1053/j.gastro.2016.07.010). A total of 725 (7%) of the colorectal cancers occurred after colonoscopy, the researchers determined. These lesions were significantly more often located in the proximal colon (odds ratio, 2.34; 95% confidence interval, 1.90-2.89) and were more likely to have DNA mismatch repair deficiency (OR, 1.26; 95% CI, 1.00-59) when compared with colorectal cancers diagnosed in patients with no prior colonoscopy. However, they also were significantly less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89). Interval colorectal cancers were particularly likely to be located in the proximal colon and/or to have DNA mismatch repair deficiency when diagnosed 3-6 years after colonoscopy, but the excess burden of these characteristics persisted up to 10 years after colonoscopy, the researchers said.
Molecular analyses of 85 postcolonoscopy colorectal cancers from one hospital indicated that 24% had DNA mismatch repair deficiency. When considering only those tumors diagnosed within 10 years after colonoscopy, 27% had KRAS/NRAS mutations, 19% had BRAF mutations, and 19% had PIK3CA mutations. The 7% of tumors with molecular features of Lynch syndrome all occurred within 10 years after index colonoscopy and accounted for a third of cases of DNA mismatch repair deficiency, reflecting the role of this mutation pathway in Lynch syndrome and its tendency to rapidly progress, the investigators said.
Notably, 38% of colorectal cancers diagnosed within a year after colonoscopy involved an incomplete examination, compared with only 16% of cases diagnosed within 1-10 years after colonoscopy, they also reported. This finding and the clinical and molecular correlates of the interval cancers “supports the popular assumption that many cancers diagnosed soon after colonoscopy result from missed lesions,” they concluded. “However, the heterogeneity in clinical and molecular features of cancers diagnosed at different time intervals suggests postcolonoscopy colorectal cancers are likely multifactorial in their etiology and clinical behavior.”
The study was supported by the Danish Cancer Society, the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institutes of Health, M.D. Anderson Cancer Center, and a University of Texas Frederick Becker Distinguished University Chair in Cancer Research. The investigators had no disclosures.
