Long-Term Incidence and Mortality of Colorectal Cancer After Endoscopic Biopsy With Normal Mucosa: A Swedish-Matched Cohort Study

INTRODUCTION Endoscopic screening reduces colorectal cancer (CRC) incidence and mortality. Individuals with a negative result are recommended to undergo rescreening within a 10-year interval, but evidence supporting this advice is limited. METHODS We performed a matched cohort study using prospectively collected data from 88,798 individuals in Sweden with normal mucosa at the first colorectal biopsy (aged ≥50 years) in the nationwide gastrointestinal epidemiology strengthened by histopathology reports (ESPRESSO) (1965-2016) and 424,150 matched reference individuals from the general population. Cox proportional hazards regression estimated multivariable hazard ratios and 95% confidence intervals (CIs) of CRC incidence and mortality of incident CRCs up to 44 years of follow-up. RESULTS In the normal biopsy and reference groups, respectively, the 20-year incidences of CRC were 3.03% and 4.53% and the 20-year mortalities of incident CRC were 0.89% and 1.54%. The multivariable hazard ratio comparing the normal biopsy and reference groups was 0.62 for CRC incidence (95% CI = 0.58-0.66, P < 0.001) and 0.56 for mortality of incident CRC (95% CI = 0.49-0.64, P < 0.001). When assessed by time interval after biopsy, lower CRC incidence and mortality were observed throughout the follow-up. The association seemed weaker for proximal colon cancer than for rectal and distal colon cancer. DISCUSSION A normal colorectal biopsy was associated with lower CRC incidence and mortality for at least 20 years after the examination. Our findings confirm previous data and suggest that the screening intervals after a normal colonoscopy could be longer than the commonly recommended 10 years. It may be time to open the discussion for a revision of the international guidelines.