Colorectal Cancer Risk Reduction After Polypectomy: Evidence Against the National Polyp Study

Dear Editor:

We read with great interest the study by Kahi et al1 showing a 67% relative risk reduction in colorectal cancer (CRC) incidence after colonoscopy screening. Before the present study, the strongest evidence supporting the adoption of colonoscopy as a screening strategy was the 76% CRC risk reduction shown by the National Polyp Study (NPS) in those who underwent removal of adenomatous polyps at the index colonoscopy.2 However, as outlined by Kahli et al, such evidence was not confirmed by subsequent studies, questioning the actual CRC reduction after polypectomy. Such a risk reduction as a result of polypectomy appears to be crucial, because it is intimately related with the overall efficacy of screening colonoscopy; the latter is obviously unrelated with the selection of patients at very low risk of CRC, such as those with a negative colonoscopy. In the present study, 6 of the 7 incident CRCs occurred in the 190 patients in postpolypectomy follow-up, so that the corresponding incidence rate of CRC in those with and without polyps at the index colonoscopy was 2.2 and 0.13 cases per 1000 person-years, respectively, when excluding prevalent cancers. Therefore, patients who underwent a polypectomy experienced a 17-fold increase of CRC incidence as compared with those with a negative index colonoscopy, also very similar to the Surveillance Epidemiology and End Results (SEER) estimate of 2.1–2.3 cases per 1000 person-years computed by the authors. Moreover, 5 of the 6 incident CRCs in postpolypectomy patients occurred in the 103 patients with one or two <10-mm tubular adenomas, corresponding to a theoretical risk of 3.4 cases per 1000 person-years, when admitting the same amount of follow-up for those with and without low-risk polyps. Therefore, postpolypectomy CRC incidence was not reduced as compared with SEER incidence, similar to what was reported in the Polyp Prevention and Wheat-Bran Fiber trials,3, 4 which was markedly different from the 76% CRC reduction reported by the NPS. Moreover, most of such CRC risk segregated in those regarded as low-risk patients, for whom an increase up to 10 years for the first postpolypectomy endoscopy has been paradoxically advocated.5 It could be argued that a long-term postpolypectomy CRC risk equal to the SEER estimate still represents a success in patients at increased CRC risk, being mainly responsible for the CRC incidence reduction shown by the authors after colonoscopy screening. However, such assumption heavily weakens the role of polypectomy in preventing CRC, as it was delineated by the NPS results, questioning the overall efficacy of colonoscopy screening, especially when compared with other competitors such as fecal tests that, different from colonoscopy, were validated by randomized studies. Therefore, the present study indirectly confirms the necessity of randomized studies when validating screening strategies, because indirect evidence, arising from cohort studies, might be subject to undetected bias that prevents its reproducibility in other settings. Moreover, the consistent discrepancy between the NPS results and those of the subsequent trials, including the present one, should question the opportunity of weakening the intensity of postpolypectomy follow-up, broadening the intervals between subsequent examinations, especially in those with a low-risk polyp at the index colonoscopy.