Methods
Study Design
Patients were identified from the population-based registry of colorectal polyps in Côte-d'Or (Burgundy, France), which includes data on all cases of colorectal adenomas diagnosed since 1976. There were 506 755 residents in the area covered by the registry, according to the 1999 census.
The study population comprised all residents of Côte-d'Or diagnosed for the first time with a colorectal adenoma between 1 January 1990 and 31 December 1999 (n=7043).
As shown in figure 1, we excluded patients with known familial polyposis or hereditary non-polyposis colorectal cancer syndrome, inflammatory bowel disease, a personal history of adenoma or colorectal cancer, or with synchronous colorectal cancer (n=770). Colorectal cancer or adenomas diagnosed within 1 year of the initial colonoscopy were assumed to have been present during the initial investigation. Thus, these lesions were considered as being present at the first colonoscopy. This strategy resulted in the exclusion of 42 patients who developed colorectal cancer during the first year after adenoma diagnosis, and patients who died or were followed-up for <1 year (n=452). The final analysis included 5779 patients.
(Enlarge Image)
Figure 1.
Study flow diagram
Information on adenoma cases is routinely obtained from all public and private pathology laboratories in the area. Pathology reports were used to classify adenomas according to histological architecture, grade of dysplasia, size and location. For patients with multiple adenomas, the most severe adenoma was used for classification. Advanced adenomas were defined as adenomas with a diameter ≥10 mm and/or a villous component and/or high-grade dysplasia (severe dysplasia or intramucosal carcinoma). Adenoma location was defined according to the 10th International Classification of Diseases for Oncology and classified into: proximal colon (caecum, ascending colon, hepatic flexure and transverse colon), distal colon (splenic flexure, descending colon and sigmoid) and rectum (rectosigmoid junction and rectum ampulla).
In France, colonoscopies are performed only by trained gastroenterologists in public or private hospital endoscopic units. The medical records of the gastroenterologists were reviewed to obtain missing information such as age, sex, family history of colorectal tumours, adenoma size and adenoma location. For the present study, all follow-up colonoscopies were collected and their findings recorded until the study end-point date (31 December 2003) or the last known follow-up date. A follow-up colonoscopy was defined as an examination performed between 1 year after first adenoma removal and the end-point date or the date of cancer diagnosis. The colonoscopy that detected colorectal cancer was considered as a follow-up colonoscopy only if the patient was asymptomatic and if the reason for colonoscopy was clearly stated as surveillance of previous colorectal lesions. The vital status of adenoma patients was obtained from multiple sources including national mortality files (National Register for the Identification of Physical Persons), gastroenterologists and general practitioners' medical records, and hospital discharge files. Follow-up information was obtained for 96.4% of the patients with adenoma included in the present study.
In addition, the cancer registry collects all cases of digestive cancers including colorectal cancers. Data are regularly collected from public and private pathology laboratories, university and local hospitals, the Comprehensive Cancer Centre, private specialists (gastroenterologists, surgeons, oncologists, radiotherapists), general practitioners, as well as from the French National Health Service and the monthly review of death certificates. The quality and comprehensiveness of registration is certified every 4 years by an audit of the National Institute for Health and Medical Research (INSERM) and of the National Public Health Institute (InVS). Cancer registry activities were approved by the Burgundy Medical Ethics Committee and the National Commission for Data Processing and Liberties (CNIL). Data from the cancer registry were used to identify patients with adenoma who developed metachronous cancer and to provide reference incidence data in the Côte-d'Or population. The registry also allows patients with a history of colorectal cancer or synchronous colorectal cancer to be identified. Only invasive colorectal cancers were considered.
Statistical Analysis
Person-time was calculated for patients with adenoma over a period beginning 1 year after the date of diagnosis of first adenoma until the date of invasive colorectal cancer diagnosis or the date of death or the last available medical follow-up or the end-point date (December 2003), whichever came first. The number of person-years was calculated by sex and 5-year age group. The sex and age-specific colorectal cancer incidence rates in the general population were obtained from the cancer registry. The expected number of colorectal cancers was calculated by multiplying incidence rates in the general population by the observed sex and age-specific number of person-years at risk in the study population. The ratio of observed to expected cases of colorectal cancer was reported as a standardised incidence ratio (SIR). The calculation of 95% CIs was based on the exact Poisson distribution. Cumulative colorectal cancer probabilities were calculated using the Kaplan–Meier method and expressed with 95% CI.
Statistical analyses were performed using STATA V.10.0 (Stata Corporation).