BACKGROUND: Post-colonoscopy colorectal cancer (PCCRC), defined as colorectal cancer (CRC) detected after a cancer-negative colonoscopy, represents a key quality indicator for CRC detection and prevention. While most PCCRC is attributed to missed lesions, few studies examine pathologic and molecular characteristics of PCCRC to assess for possible de novo cancer formation causing PCCRC. AIM: The aim of this study was to identify cases of PCCRC where prior colonoscopy was adequate (A-PCCRC) versus inadequate (I-PCCRC) and compare both subtypes with spontaneous CRC (sCRC) in terms of patient factors, histopathology and molecular characteristics. METHODS: This was a 12-year retrospective population-based study using a data set from the Western Australian Cancer Registry between 2000 and 2011. A-PCCRCs were identified by excluding lesions likely missed due to procedural factors or incomplete prior resection at index colonoscopy performed within 3-36 months of cancer diagnosis. Histopathological review and next-generation sequencing were conducted on subsets of patients with A-PCCRC and sCRC. Statistical analysis included univariable and multivariable regression models and chi-squared and Wilcoxon rank sum tests. RESULTS: A total of 524 (3.81%) cases of PCCRC were identified out of 13 757 cases of CRC
272 were A-PCCRC (1.98%) and 252 I-PCCRC (1.83%). Female sex, older age and proximal location were associated with A-PCCRC. Mutations in the PIK3CA gene were less common in A-PCCRC compared to sCRC. CONCLUSION: A significant percentage of PCCRC occurred despite adequate prior colonoscopy. Missed sessile serrated lesions may contribute to many of these cases
however, further studies are required to examine possible de novo cancer as a cause of PCCRC that may involve unique biological pathways.