Assessment of volumetric growth rates of small colorectal polyps with CT colonography: a longitudinal study of natural history

Abstract

Background: The clinical relevance and in-vivo growth rates of small (6-9 mm) colorectal polyps are not well established. We aimed to assess the behaviour of such polyps with CT colonography assessments.

Methods: In this longitudinal study, we enrolled asymptomatic adults undergoing routine colorectal cancer screening with CT colonography at two medical centres in the USA. Experienced investigators (PJP, DHK, JLH) measured volumes and maximum linear sizes of polyps in vivo with CT colonography scans at baseline and surveillance follow-up. We defined progression, stability, and regression on the basis of a 20% volumetric change per year from baseline (20% or more growth classed as progression, 20% growth to -20% reduction classed as stable, and -20% or more reduction classed as regression). We compared findings with histological subgroups confirmed after colonoscopy when indicated. This study is registered with ClinicalTrials.gov, number NCT00204867.

Findings: Between April, 2004, and June, 2012, we screened 22,006 asymptomatic adults and included 243 adults (mean age 57·4 years [SD 7·1] and median age 56 years [IQR 52-61]; 106 [37%] women), with 306 small colorectal polyps. The mean surveillance interval was 2·3 years (SD 1·4; range 1-7 years; median 2·0 years [IQR 1·1-2·3]). 68 (22%) of 306 polyps progressed, 153 (50%) were stable, and 85 (28%) regressed, including an apparent resolution in 32 (10%) polyps. We established immediate histology in 131 lesions on colonoscopy after final CT colonography. 21 (91%) of 23 proven advanced adenomas progressed, compared with 31 (37%) of 84 proven non-advanced adenomas, and 15 (8%) of 198 other lesions (p<0·0001). The odds ratio for a growing polyp at CT colonography surveillance to become an advanced adenoma was 15·6 (95% CI 7·6-31·7) compared with 6-9 mm polyps detected and removed at initial CT colonography screening (without surveillance). Mean polyp volume change was a 77% increase per year for 23 proven advanced adenomas and a 16% increase per year for 84 proven non-advanced adenomas, but a 13% decrease per year for all proven non-neoplastic or unresected polyps (p<0·0001). An absolute polyp volume of more than 180 mm(3) at surveillance CT colonography identified proven advanced neoplasia (including one delayed cancer) with a sensitivity of 92% (22 of 24 polyps), specificity of 94% (266 of 282 polyps), positive-predictive value of 58% (22 of 38 polyps), and negative-predictive value of 99% (266 of 268 polyps). Only 16 (6%) of the 6-9 mm polyps exceeded 10 mm at follow-up.

Interpretation: Volumetric growth assessment of small colorectal polyps could be a useful biomarker for determination of clinical importance. Advanced adenomas show more rapid growth than non-advanced adenomas, whereas most other small polyps remain stable or regress. Our findings might allow for less invasive surveillance strategies, reserving polypectomy for lesions that show substantial growth. Further research is needed to provide more information regarding the ultimate fate of unresected small polyps without significant growth.

Funding: US National Institutes of Health, National Cancer Institute.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Flow diagram of study cohort.

Figure 2. Categorization of polyp growth according to histologic subgroup

Polyp growth categories are shown according to the baseline assumption of ±20% volume change per year. Proven advanced adenomas (n=24) demonstrate a strong tendency towards positive growth, whereas growth amongst proven non-advanced adenomas (n=84) is more intermediate, and all other subgroups, including proven non-neoplastic polyps (n=24) tend to remain stable or regress.

Figure 3. Interval progression of small colorectal polyps in two patients

Top row: 3D colon map from CTC (left image) shows the location of a small sigmoid polyp (red dot), which measured 7.8 mm at the index screening examination (middle image). Polyp segmentation for volume measurement is shown on both 3D and 2D (inset) views. At follow-up CTC one year later (right image), the polyp grew only 0.8 mm but showed a 50% increase in volume (to 205 mm3). The lesion proved to be a tubulovillous adenoma after polypectomy at same-day colonoscopy (inset). Bottom row: 3D colon map shows (left image) shows the location of three small polyps in the right colon. The patient was enrolled in the study after refusing same-day colonoscopy. 3D images from the index CTC (middle image) and surveillance CTC 16 months later (right image) show a small sessile polyp in the proximal transverse colon that increased from 6.0 mm to 8.0 mm, and increased in volume by 203% (153%/year). Similar growth was seen with the two cecal polyps. The polyp in the transverse colon proved to be a tubular adenoma (the fastest-growing non-advanced adenoma in the study), whereas the cecal lesions proved to be advanced (tubulovillous) adenomas.

Figure 4. Polyp regression

3D colon map (left image) shows the location of a 6.2 mm polyp in the descending colon (red dot) detected at screening CTC in 2005 (2nd column). Surveillance CTC in 2007 (3rd column) showed no interval change in size. By the time of continued surveillance in 2011 (4th column), 6.4 years after the initial CTC, the polyp had completely resolved, which was observed in 10% of small polyps overall. Detection of the small polyp on the intermediate CTC in 2007 essentially excludes the possibility of a false-positive interpretation.

Figure 5. Polyp volume change according to histologic subgroup

Mean polyp volume changes per year (including 95% confidence intervals) are shown for all polyps (n=306), advanced adenomas (n=23), non-advanced adenomas (n=84), non-neoplastic polyps (n=24), and unresected or resolved polyps (n=174). On average, positive growth over time is seen with neoplasms (adenomas), especially with advanced lesions, whereas all other small polyps tended to show an overall decrease in size over time. The one case with delayed cancer diagnosis is not included in the graph, as it was not only an extreme outlier but also because tissue diagnosis was established years after surveillance CTC.