Of 3876 subjects selected for inquiry, 3,627 (93.6%) responded. Non response was primarily due to death (N=125, 3.2%) and inability to contact or refusal to participate (N=124, 3.2%). The characteristics of the included population are presented in and are reflective of the overall PLCO population (12
). Sixty percent were men, 93.1% were white and the majority had some college or a college degree (68.6%). Based on the most advanced lesion at diagnostic colonoscopy after screening FSG, 1342 subjects had advanced adenoma (AA), 1022 had non-advanced adenoma (NAA) (N=117 with ≥3 NAA and N=905 with 1-2 NAA), and 1263 had non adenomatous findings (NA). Subjects were followed for a median of 8.9 years (range 5.4 – 12.0).
Characteristics of Study Population (N=3,627)
The cumulative probability of a surveillance colonoscopy () within 5 years was 58.4% in the advanced adenoma group, 57.5% in those with ≥3 non-advanced adenomas, 46.7% in those with 1-2 non-advanced adenoma, and 26.5% in subjects with no adenoma (p<0.0001 for AA or ≥3 NAA vs. 1-2 NAA or NA, and for 1-2 NAA vs. NA). A Kaplan-Meier probability curve of utilization is presented in .
Cumulative Kaplan-Meier Estimates of Probability of Surveillance Colonoscopy
Figure 1 Kaplan-Meier probability curve for surveillance colonoscopy use by year from baseline diagnostic colonoscopy for subjects with Advanced Adenoma (Solid Line), ≥3 Non-advanced Adenoma (dotted line), 1-2 Non-advanced Adenoma (dashed line), and no (more ...)
Some subjects received more than one surveillance colonoscopy. In the number and weighted percent of colonoscopy exams within 7 years, among subjects with ≥ 7 years of follow-up (N=3052) is charted. Within 7 years, 33.2% of subjects with advanced adenoma received ≥ 2 surveillance exams versus 26.9% for those with ≥3 NAA, 18.2% for those with 1 or 2 NAA, and 10.4% for those with non-adenomatous findings. All pair wise comparisons were significant at a p≤0.0001 except for AA vs. ≥3 NAA (p=0.2) and ≥3 NAA vs. 1 or 2 NAA (p=.02).
Number of Surveillance Colonoscopy Exams Within the First 7 years of Follow-up1
Among subjects with advanced adenoma, 27.3% did not undergo surveillance colonoscopy within 7 years (). To evaluate the effect of co-morbid illness on underutilization of surveillance among subjects with advanced adenoma or ≥ 3 non-advanced adenomas we calculated a modified co-morbidity index score. Of 896 with surveillance, 791 (88.3%) had an index of 0 or 1, and 105 (11.7%) had a score ≥2, whereas of 293 without surveillance, 247 (84.3%) had an index of 0 or 1, and 46 (15.7%) had a score ≥2, (p=.08). If we restricted the sample of advanced adenoma subjects to those under age 70 with a co-morbidity index of 0 or 1, the results were similar, with 25.4% not having surveillance.
In a logistic regression model to assess the lack of surveillance after 7 years in subjects with advanced adenoma (N=1079) that included age, gender, family history of colorectal cancer (CRC), time of enrollment in the trial, education, inadequate preparation/incomplete colonoscopy, and comorbidity, the factors associated with lack of surveillance were age, earlier enrollment, and family history. Subjects 70-74 at time of entry into the trial were more likely to not undergo a surveillance exam as compared to those 55-69 (OR=1.5, 95% CI 1.0-2.2, p=0.03). After 7 years, 35.6% in the 70-74 year old age group as compared to 26.1% in the 55-69 year group did not receive surveillance. Subjects without a family history of CRC in a first degree relative were also more likely to not have surveillance (26.3% vs. 15.5% of those with a family history) (OR=2.2, 95% CI 1.4-3.6 (p<.001)), as were subjects enrolled earlier in the trial (subjects slated for year 3 as opposed to year 5 repeat screening) (OR=1.4, 95% CI 1.0-1.8 (p=.04)).
The utilization of 1st and 2nd surveillance exams among subjects with ≥7 years of follow-up with 1 or 2 non advanced adenomas or no adenomas at baseline colonoscopy is presented in . The median time in years (25th and 75th percentile) from the baseline to the first surveillance and from the first to the second surveillance is presented on the bottom of each panel. In the far right of the figures, results of surveillance in “pure” subgroups, in subjects with no family history of CRC, complete colonoscopy with adequate preparation at baseline and at 1st surveillance, without symptoms, and with no adenoma diagnosed at the 1st surveillance exam are presented.
Surveillance Colonoscopy Use by Baseline Histologic Status
describes subjects with 1-2 non-advanced adenomas at baseline. Only 4.3% of the 69.7% who underwent a 1st surveillance exam did so for symptoms. Among the 394 (70.6%) whose 1st surveillance exam showed no adenoma, 203/394 (51.5%) had a second surveillance exam, only 18 of which (8.9%) were performed for symptoms. The median time for the 2nd surveillance exam in these asymptomatic subjects, after 1 or 2 non-advanced adenomas at baseline and no adenoma at the 1st surveillance was 3.9 years (). In the subgroup without family history, symptoms, or incomplete/inadequate preparation, 131/299 (43.8%) underwent a 2nd surveillance examination at a median of 4.0 years from the 1st surveillance exam. Utilization of 2nd surveillance in this group was similar to that of all subjects without an adenoma at the 1st surveillance (185/394, 47.0%).
Of the 1026 subjects with no adenoma at the baseline exam, 597 (58.2%) underwent a first surveillance within 7 years, only 75 (12.5%) of whom did so for symptoms (). The 1st surveillance exam was performed at a median of 3.9 years from the baseline exam. Among 411 subjects whose 1st surveillance exam again showed no adenoma, 162 had a second surveillance exam in the absence of symptoms. This second exam was performed at a median of 3.2 years from the 1st. Of these 162 individuals, 31 (19.1%) had a family history of CRC and 18 (11.1%) had either an inadequate preparation or an incomplete colonoscopy at the 1st surveillance, leaving over 69% without an identifiable reason for a repeat surveillance exam. In the “pure” subgroup without a family history and with complete colonoscopy, 104/294 (35.4%) underwent a 2nd surveillance at a median of 3.3 years from the 1st exam.
In a logistic model including age, gender, family history of colorectal cancer (CRC), time of enrollment in the trial, education, inadequate preparation/incomplete colonoscopy examining risk factors for receiving a 1st surveillance colonoscopy within 7 years among subjects with no adenoma at baseline and in the absence of symptoms (N=951), only family history was significantly associated with surveillance (OR=2.0, 95%CI 1.3-2.9, p<.001).
We examined the extent to which incomplete colonoscopy due to lack of cecal visualization or inadequate preparation at the baseline examination may have contributed to surveillance utilization among low risk subjects. A total of 574 subjects with either no adenoma at baseline colonoscopy (N=273) or 1 or 2 non-advanced adenomas at baseline colonoscopy (N=301) had a 1st surveillance colonoscopy within 4 years, in the absence of symptoms. Among colonoscopy reports of those with no adenoma, only 8/273 (2.9%) and among those with 1 or 2 NAA, 11/301 (3.7%), indicated lack of cecal visualization at the baseline colonoscopy, and 18/273 (6.6%) and 16/301 (5.3%) respectively indicated an inadequate preparation at the baseline colonoscopy.
We examined the extent to which multiple physician examiners may have contributed to utilization of colonoscopy among low risk subjects. Among 162 asymptomatic subjects () with no adenoma at baseline nor at the 1st surveillance, with a second surveillance exam, 109/162 (67.3%) had all 3 exams performed by either the same physician, at the same location, or within the same physician practice and only 8 patients (4.9%) were examined under 3 different circumstances.
Among subjects (N=99) who reported not having a colonoscopy but in whom records were pursued to see if the subject’s negative report could be contradicted, no report of a colonoscopy procedure could be recovered in 91 (91.9%).
Indication for colonoscopy performance showed that of the 4853 colonoscopies in 3627 subjects, only 353 (7.3%) were attributed to symptoms, 3936 (81.1%) were performed for follow up of a previous polyp, 58 (1.2%) for family history, 269 (5.5%) as a consequence of an interval PLCO screening exam, and 237 (4.8%) for other reasons. Analysis of the results across the 9 screening centers demonstrated a range of surveillance at 5 years for subjects with advanced adenoma from 32.6 to 75.6%, and for the non adenoma group from 13.6 to 34.1%.
The yield of surveillance exams in this cohort including adenomatous findings and the detection of 5 interval cancers has been reported (13