Ongoing colorectal cancer risk despite surveillance colonoscopy: the Polyp Prevention Trial Continued Follow-up Study

Abstract

Background Despite regular colonoscopy, interval colorectal cancer (CRC) may occur. Long-term studies examining CRC rates in patients with previous colonoscopy are lacking. Objective We examined the rate of interval CRC in the Polyp Prevention Trial-Continued Follow-up Study (PPT-CFS), an observational study of participants which began after the Polyp Prevention Trial (PPT) ended. Design Prospective Setting A national U.S. community-based polyp prevention trial Main Outcome Measurements Medical records of CRC were collected, reviewed, and abstracted in a standardized fashion. Results Among 2,079 PPT participants, 1,297 (62.4%) agreed to participate in the PPT-CFS. They were followed for a median of 6.2 years after 4.3 years of median follow up in the main PPT. Nine cases of CRC were diagnosed over 7,626 person years of observation (PYO) for an incidence rate of 1.2/1000 PYO. The ratio of CRCs observed compared to that expected by SEER was 0.64 (95% CI 0.28–1.06). Including all CRCs (N=22) since the beginning of the PPT trial, the observed compared to expected rate by SEER was 0.74 (95% CI 0.47–1.05). Of patients who developed CRC in the PPT-CFS, 78% had a history of an advanced adenoma compared to only 43% among patients who remained cancer-free (p=0.04). Limitations A relatively small number of interval cancers were detected. Conclusions Despite frequent colonoscopy during the PPT trial, in the years subsequent to the trial, there was a persistent ongoing risk for cancer. Subjects with a history of advanced adenoma are at increased risk for subsequent cancer and should be followed closely with continued surveillance.

Colonoscopy Quality Assessment

“…Several studies evaluating interval CRCs found that these cancers can be attributed to incomplete polypectomy in about 10% to 30% of cases 13,20,22,64,65 . Since ADR is essentially geared at assessing detection and not resection, the inadequate quality in these cases would not be reflected by measuring the ADR.…”

Follow Up and Recurrence of Colorectal Cancer

“…Leung and colleagues studied colorectal cancer risk despite surveilance colonoscopy and concluded that despite frequent colonoscopy there was a persistent ongoing risk of cancer in the years after the trial. Subjects with a history of advanced adenoma are at increased risk of subsequent cancer and should be followed closely with continued surveillance (Leung et al, 2010). Importantly, the performance of annual colonoscopy has not been shown to improve fiveyear survival.…”

Quality assurance in colonoscopy for colorectal cancer diagnosis

“…Lower rates are likely to be explained by poor examination quality. Some incidental CRC's are probably related to missed adenomas (15,47). However, complete resection of early CRC by an experienced endoscopist is possible, making polypectomy curative.…”

“…Protocols for routine monitoring of interval cancers are being developed (46). A proportion of interval cancers occur due to aggressive tumour biology (17), but missed lesions and incomplete polyp removal are important contributing factors (15,16).…”

“…Adenoma miss rate increases with the smaller size of polyps (11), and even colon cancers can be missed during routine colonoscopy (12,13). Early interval cancers can occur (14), especially in the proximal colon in patients with a history of advanced adenomas, and most were probably preventable and believed to be caused by missed or incomplete resected polyps (15,16). However, some interval cancers do appear to result from rapid tumor growth and the prevalence of microsatellite instability, and may not represent a failure of colonoscopy (17).…”