CHARACTERISTICS OF METACHRONOUS COLORECTAL-CARCINOMA OCCURRING DESPITE COLONOSCOPIC SURVEILLANCE

PURPOSE: Metachronous colorectal cancer still occurs in a small percen tage of patients, despite colonoscopic surveillance. Cancers in heredi tary nonpolyposis colorectal cancer for which there is a high risk of metachronous cancer show distinctive DNA changes termed replication er rors (RER+). Ten to 20 percent of sporadic colorectal cancers are also RER+. The aim of this study was to identify factors predictive of met achronous colorectal cancer, despite colonoscopic surveillance. Clinic opathologic characteristics and RER status of cancers were examined. M ETHODS: Colorectal tal cancer patients, who entered into a surveillanc e program of being examined with colonoscopy within six months of surg ery and then at intervals of three years thereafter, were reviewed. Th e 433 patients compliant with the protocol who had had more than one c olonoscopy had been followed up for a mean of 3.8 +/- 2.2 years. DNA w as extracted from archival paraffin-embedded cancer tissue for determi nation of RER status. RESULTS: Ten cases of metachronous cancer were i dentified, giving a rate of 0.61 percent per year. The site of the ind ex cancer in patients who later developed metachronous cancer was pred ominantly proximal (P = 0.0007), and these cancers were more likely to have mucinous histology (P < 0.0005). Three of 10 (30 percent) index cancers were RER+, which was not significantly different from unselect ed series of control colorectal cancers in which 20 of 108 (18.5 perce nt) were RER+. DISCUSSION: This study documents the rate of metachrono us cancer among patients compliant with a defined colonoscopic screeni ng program and suggests that the risk is highest in patients with a pr oximal mucinous cancer. RER status does not appear to be a very strong predictive factor, and this study does not support its use as a guide to the frequency of surveillance colonoscopy. More data would be requ ired to determine if RER positivity conferred a relative risk of 3.3 o r less.