Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up

Abstract

Abstract: The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS.

Prevention relevance: Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.

Figure 1.

Trial profile showing distribution of participants by randomisation group and length of follow-up together with counted outcomes of cancer diagnoses among participants; CRC, colorectal cancer; LS Ca, Lynch syndrome associated cancers (other than colorectal cancer).

Figure 2.

Time to first colorectal cancer and time to first non-colorectal cancer Lynch syndrome cancer in all CAPP2 study participants followed up for 10 years and for 20 years in England, Finland, and Wales. Cox proportional hazards (HRs and 95% CIs) comparing those on Resistant Starch vs. those on placebo and depicted by Cumulative incidence curves (n = 918). A, Intention-to-treat analysis (n = 463 Resistant Starch, 455 placebo) by randomisation group. B, Per-protocol analysis of all those achieving 2 years Resistant Starch or placebo (n = 521). C, Intention-to-treat analysis for non-colorectal cancer Lynch syndrome cancers. D, Per-protocol analysis for non-colorectal cancer Lynch syndrome cancers.