Contrasts in colorectal cancer incidence and mortality in screening trials of sigmoidoscopy versus colonoscopy (NordICC)

Background Interim 10-year results from the Nordic-European Initiative on Colorectal Cancer (NordICC), a randomized controlled trial (RCT) of screening colonoscopy, demonstrated a statistically significant reduction in colorectal cancer (CRC) incidence but not mortality, contrary to results from four flexible sigmoidoscopy (FS)-RCTs. Methods We constructed CRC incidence and mortality Kaplan-Meier curves through 10 years to standardize comparisons across RCTs, and examined CRC screen-detection and stage. Novel analyses of one FS-RCT (Prostate, Lung, Colorectal, and Ovarian cancer screening trial [PLCO]) assessed year-by-year mortality in screen-detected CRCs. Results At 10 years, all five RCTs demonstrated statistically significant CRC incidence reductions with screening (ratios = 0.77 [95%CI 0.70–0.84] to 0.82 [0.69–0.97] vs controls; P ≤ .011). Two FS-RCTs and NordICC showed no significant CRC mortality reduction (ratios = 0.84 [0.64–1.10] to 0.90 [0.69–1.18]; P = .10–0.23). In three FS-RCTs and NordICC, relative reductions were greater in CRC incidence than CRC mortality, but only NordICC reported higher CRC mortality with screening vs controls for the first 7 years. In contrast, PLCO observed fewer CRC deaths with screening by year 2 (ratio = 0.59, P = .03), and screen-detected CRCs were less often advanced (OR = 0.26; P < .001) or fatal (ratio = 0.50; P < .001). Conclusions After 10 years, NordICC is similar to two FS-RCTs in observing statistically significant reductions in CRC incidence but not CRC mortality. However, only NordICC observed greater CRC mortality with screening vs controls for 7 years. Granular analyses of CRC cases and deaths in NordICC, paralleling our PLCO analyses, could provide insight into why CRC mortality results differ in NordICC vs FS-RCTs.