Abstract
Background and Aims:
Because data on metachronous risk for patients with index proximal 5- to 9-mm hyperplastic polyps (HPs) are limited, the clinical significance of these polyps is unclear. Conversely, published data suggest that sessile serrated polyps (SSPs), traditional serrated adenomas (TSAs), and large (≥1 cm) HPs are high-risk lesions requiring close surveillance. We used data from the New Hampshire Colonoscopy Registry (NHCR) to examine the risk of metachronous large SPs and advanced neoplasia in patients with 5- to 9- mm proximal HPs.
Methods:
We included adults with at least 1 polyp resected at index colonoscopy and a surveillance examination 12 months or more after index. Outcomes were risk for metachronous large (≥1 cm) SPs and advanced neoplasia (≥1 cm, villous elements, high-grade dysplasia or colorectal cancer [CRC]). Individuals were hierarchically stratified by the most significant index SP. The risks for adults with proximal 5- to 9-mm HPs at index examination were compared with individuals with index findings of large (≥1 cm) HPs or any SSPs or TSAs, nonsignificant HPs (<1 cm in rectosigmoid or <5 mm anywhere in colon), high-risk adenomas (advanced neoplasia or ≥3 adenomas, no SPs), and low-risk adenomas (no SPs). We present absolute and adjusted risks of metachronous polyps from a regression model that included age, sex, body mass index, smoking, previous polyp history, family history of CRC, year of diagnosis, endoscopist SP detection rates, and months to surveillance examination.
Results:
A total of 8560 NHCR participants were included (44.8% women; average age, 59.0 years; standard deviation, 9.1). Similar to those with large HPs or any SSPs/TSAs at index examination (odds ratio, 7.63; 95% confidence interval, 4.78–12.20), individuals with proximal 5- to 9-mm HPs had an elevated risk for metachronous large SPs (odds ratio, 4.77; 95% confidence interval, 2.54–8.94) as compared with adults with low-risk conventional adenomas.
Conclusions:
NHCR data suggest that similar to adults with large HPs or any SSPs or TSAs at index examination, individuals with index 5- to 9-mm HPs proximal to the sigmoid are at an increased risk for metachronous large SPs. These novel data suggest that close surveillance intervals may be appropriate for patients with 5- to 9-mm proximal HPs.
Serrated polyps (SPs) are part of a pathway that accounts for a significant proportion of colorectal cancer (CRC).1,2 Thus, adequate endoscopic detection, resection, and surveillance are crucial for patients with these lesions detected at colonoscopy. Furthermore, identifying those SPs that may place the affected individual at risk for future clinically significant lesions is critical for effective CRC prevention through colonoscopy. SPs include hyperplastic polyps (HPs), sessile SPs (SSPs), and traditional serrated adenomas (TSAs).1 With regard to malignant potential, TSAs have dysplasia and SSPs can develop dysplasia, and individuals with SSPs or TSAs have been shown to have an increased long-term risk of CRC similar to that in individuals with conventional advanced neoplasia.3 In light of these findings, both 2012 and 2020 surveillance guidelines from the U.S. Multi-Society Task Force (USMSTF) for CRC suggest that patients with TSAs should have surveillance colonoscopy in 3 years.4,5 The USMSTF also recommends close surveillance for patients with SSPs, with examinations at 3 or 5 years after index colonoscopy, depending on polyp size, number, and the presence or absence of dysplasia.
In contrast to SSPs and TSAs, the metachronous risk in patients with HPs is less well understood. HPs <1 cm, especially those in the rectosigmoid colon, are considered to have a benign course without malignant potential. Because individuals with large (≥1 cm) SPs, including HPs, have been shown to have an increased long-term risk for CRC,6–8 experts have recommended close surveillance in adults with large HPs. This is reflected by the current USMSTF guidelines that recommend 3- to 5-year surveillance intervals for individuals with large HPs.5 It is less clear whether HPs proximal to the sigmoid colon and 5 to 9 mm in size also require such close surveillance. Previous studies involving pathologic reassessment of lesions previously diagnosed as HPs suggest that many HPs >5 mm may actually be appropriately diagnosed as SSPs and thus considered significant lesions.9,10 As a result, 1 expert panel has suggested 5-year surveillance intervals for individuals with at least one 5- to 9-mm HP proximal to the sigmoid colon.2 However, as highlighted in recently published guidelines from the USMSTF,5 data are limited regarding the risk of subsequent advanced outcomes in patients with 5- to 9- mm HPs proximal to the sigmoid colon.
Selecting an appropriate outcome for assessing the risk of index SPs is a crucial consideration. Long-term CRC risk is the ultimate outcome of interest; however, because it is both rare and slow to develop, CRC alone is often not a practical research outcome. The more commonly used outcome is the risk of metachronous (future) polyps in adults with polyps resected at index colonoscopy. For conventional adenomas, the standard outcome for investigation is the metachronous risk for high-risk adenomas, which include adenomas 1 cm, adenomas with villous elements or high-grade dysplasia, 3 or more adenomas, or adenocarcinoma (CRC). However, prior research by the New Hampshire Colonoscopy Registry (NHCR) and others suggests that patients with only clinically significant SPs (CSSPs) such as SSPs, TSAs, or large HPs at index examination are not at increased risk for metachronous high-risk adenomas.11–14 Conversely, these studies suggest that individuals with these CSSPs are at increased risk for metachronous large (≥1 cm) SPs. Thus, large SPs are the most clinically relevant outcome to use in assessing patients with index SPs. Our goal was to use data from the NHCR to examine the metachronous risk of large SPs in patients with 5- to 9-mm proximal HPs at index colonoscopy. We also examined the risk for metachronous AAs.
METHODS
Population
Our cohort included patients in the NHCR database with 2 colonoscopies at least 12 months apart between 2005 and 2018. Before colonoscopy, patients complete a self-administered patient questionnaire to collect data on demographic factors, health behaviors, and family and personal history of both polyps and CRC. Endoscopists or endoscopy nurses completed the NHCR colonoscopy procedure form immediately after the examination. Data collected were detailed indication for the examination, findings, and quality of bowel preparation.
The NHCR requests pathology reports for all colonoscopies with findings directly from the pathology laboratory used by each participating endoscopy facility. Trained NHCR staff abstract and enter these pathology findings into the NHCR database, including location, size, and histology of each polyp matching individual polyp-level pathology data with information from the colonoscopy procedure form.15 All data collection and study procedures were approved by the Committee for the Protection of Human Subjects at Dartmouth College (study no. 00015834) and by other relevant human subjects reviewing bodies at participating sites.
Cohort
We included data from individuals with at least 1 SP or conventional adenoma detected at index examination and a surveillance examination performed at least 12 months after the index. Examinations that were incomplete or had poor bowel preparation were excluded, as were high-risk individuals with familial syndromes or inflammatory bowel disease.
Exposure variable
Individuals were hierarchically stratified (as outlined below in Statistical approach) by the most significant SP finding at index colonoscopy. Therefore, some groups could have more than 1 lesion. For example, some people in the large HP or SSP or TSA group might also have some 5- to 9-mm proximal HPs. Patients with synchronous SPs and adenomas were included in the serrated groups, and thus no individuals with SPs were included in the conventional adenoma groups.
The group of interest included those individuals with 5- to 9-mm HPs proximal to the sigmoid colon. We compared the risk for adults with these lesions with other individuals with index polyps. The exposure categories were large (≥1 cm) HPs or any SSP or TSA, 5- to 9-mm proximal HPs, nonsignificant HPs (<1 cm in the rectosigmoid colon or <5 mm and proximal to the sigmoid colon), high-risk adenomas (AAs or ≥3 tubular adenomas of any size) with no SPs, and low-risk adenomas with no SPs. AAs were defined as adenomas ≥1 cm or those with villous elements, high-grade dysplasia, or CRC.
Covariates
Covariates included patient age, sex, body mass index (BMI), family history of CRC (defined as ≥1 first-degree relative with CRC), history of colorectal polyps before index examination, smoking, year of diagnosis of index lesions, and months to surveillance examination (greater than vs less than or equal to the median follow-up of 54 months). To account for the potential of missed large SPs being detected as new lesions at subsequent colonoscopy, we added year of detection as a covariate to the logistic regression analysis because SP detection has increased over the past decade. Another covariate was the CSSP (any SSP or TSA, any HP ≥1 cm, or HP 5–9 mm proximal to the sigmoid colon) detection rate for the endoscopist performing the examinations. This was calculated by dividing the total number of screening examinations in which a CSSP was found by the total number of screening examinations. We calculated detection rates for index and follow-up examinations, both of which were dichotomized by 7%, a rate we previously identified as the median rate for those endoscopists who met the benchmark adenoma detection rate of 25% or more.16 All variables were categorical except for age, BMI and year of diagnosis, which were continuous variables.
Statistical approach
Outcomes were the absolute and adjusted risk of large (≥1 cm) SPs or advanced neoplasia, strati fied by index findings into 5 categories: large (≥1 cm) HPs or any SSP or TSA, 5- to 9-mm HPs proximal to the sigmoid colon, nonsignificant HPs (<1 cm in the rectosigmoid colon or <5 mm and proximal to the sigmoid colon), high-risk adenomas (advanced neoplasia or ≥3 tubular adenomas of any size) with no SPs, and low-risk adenomas with no SPs. For the large SP outcome, index findings of low-risk adenoma was the reference group (order shown above). For the AA outcome, index findings of nonsignificant HPs were the reference group: high-risk adenoma, low-risk adenoma, large HP or any SSP/TSA, 5- to 9-mm proximal HP, and nonsignificant HP.
We used the χ2 test for trend and the Fisher exact test to evaluate categorical variables. Wilcoxon rank sum and Mann-Whitney tests were used for nonparametric continuous variables. We performed univariate analyses and multivariable logistic regression models comparing predictors of large SPs and AAs. Covariates in the multivariable analysis included age, sex, BMI, history of colorectal polyps before index examination, family history of CRC, months to surveillance examinations, year of diagnosis of index lesions, CSSP detection rates for index and surveillance examinations, and smoking (never, past, or current).
RESULTS
A total of 8560 NHCR participants were included in this analysis (44.8% women; average age, 59.0 years; standard deviation, 9.1). The mean follow-up to surveillance examination was 53.8 months (standard deviation, 24.5). The median CSSP detection rates were 5.8% and 7.2% for index and surveillance examinations, respectively. After stratification, each group contained the following: large HPs or any SSP or TSA, n = 1103; 5- to 9-mm HPs proximal to the sigmoid, n = 376; nonsignificant HPs, n = 2484; low-risk adenomas with no SPs, n = 2962; and high-risk adenomas with no SPs, n = 1635 (Table 1). Ninety-eight individuals (8.9%) had synchronous 5- to 9-mm proximal HPs and large HP or any SSP/TSA. Patient characteristics, stratified by index colonoscopy findings, are shown in Table 1.
TABLE 1.
Patient characteristics stratified by index examination findings (n = 8560)
| No. with findings on index exam | 376 | 2484 | 1103 | 1635 | 2962 |
| Age, y | 58.5 ± 9.4 | 57.9 ± 9.2 | 58.6 ± 9.3 | 60.9 ± 9.7 | 59.0 ± 9.1 |
| Sex, male | 54.5 (205) | 46.5 (1154) | 48.1 (531) | 37.1 (606) | 45.2 (1339) |
| Body mass index, kg/m2 (continuous) | 28.9 ± 6.5 | 29.1 ± 6.0 | 28.9 ± 6.5 | 29.2 ± 6.0 | 28.3 ± 5.9 |
| Family history (first-degree relative) | 29.0 (109) | 27.6 (686) | 21.8 (240) | 20.5 (335) | 23.7 (702) |
| Adenomas on index exam | 44.4 (167) | 44.8 (1112) | 46.3 (473) | 100.0 (1635) | 100.0 (2962) |
| Smoking | |||||
| Never | 38.2 (917) | 41.7 (153) | 43.2 (684) | 43.2 (684) | 50.6 (1450) |
| Past | 45.8 (1100) | 46.3 (170) | 46.9 (743) | 46.9 (743) | 41.8 (1199) |
| Current | 16.0 (383) | 12.0 (44) | 10.0 (158) | 10.0 (158) | 7.6 (217) |
| Time to follow-up exam, mo | 59.3 ± 27.7 | 60.7 ± 27.3 | 41.4 ± 21.4 | 40.2 ± 20.5 | 59.2 ± 19.0 |
Values are % (n) or mean ± standard deviation.
HP, Hyperplastic polyp; SP, serrated polyp; SSP, sessile serrated polyp; TSA, traditional serrated adenoma.
HPs <1 cm in rectosigmoid colon or <5 mm and proximal to sigmoid colon.
Similar to those with large HPs or SSPs/TSAs at index examination, the absolute risk for metachronous large SPs was elevated in adults with 5- to 9-mm proximal HPs as compared with those with nonsignificant HPs or only conventional adenomas (Table 2). After adjusting for covariates, we again observed similar findings, that individuals with only 5- to 9-mm HPs had an elevated risk for metachronous large SPs (odds ratio [OR], 4.77; 95% confidence interval [CI], 2.54–8.94) as compared with those with low-risk conventional adenomas. The highest risk was observed in those with large HPs, SSPs, or TSAs (OR, 7.63; 95% CI, 4.78–12.20). However, those with only nonsignificant HPs had a lower risk (OR, 2.13; 95% CI, 1.32–3.44) as compared with low-risk adenoma (Table 2).
TABLE 2.
Risk for metachronous large (≥1 cm) SPs and advanced neoplasia on surveillance examination for 5- to 9-mm proximal HPs as compared with other index findings (total sample)
| Metachronous risk large SPs | Metachronous risk advanced neoplasia | ||||||
|---|---|---|---|---|---|---|---|
| Large (≥1 cm) HPs or any SSP/TSA | 1103 | 8.8 (97) | 7.63 (4.78–12.20) | Large (≥1 cm) HPs or any SSP/TSA | 1103 | 4.8 (53) | .95 (.66–1.38) |
| 5- to 9-mm proximal HP (exposure group) | 376 | 4.8 (18) | 4.77 (2.54–8.94) | 5- to 9-mm proximal HP (exposure group) | 376 | 8.0 (30) | 1.83 (1.19–2.81) |
| Nonsignificant HPs† | 2484 | 2.1 (53) | 2.13 (1.32–3.44) | Nonsignificant HPs† | 2484 | 4.5 (111) | 1.0 (reference) |
| Low-risk adenomas (no SPs) | 2962 | 1.0 (30) | 1.0 (reference) | Low-risk adenomas (no SPs) | 2962 | 4.3 (127) | 1.07 (.82–1.40) |
| High-risk adenomas (no SPs) | 1635 | 2.0 (33) | 1.90 (1.10–3.29) | High-risk adenomas (no SPs) | 1635 | 9.7 (158) | 2.05 (1.55–2.70) |
Values are % (n) unless otherwise defined.
AA, Advanced adenoma; HP, hyperplastic polyp; SP, serrated polyp; SSP, sessile serrated polyp; TSA, traditional serrated adenoma.
Adjusted for age, sex, body mass index, previous neoplasia, smoking, family history of colorectal cancer, endoscopist clinically significant SP detection rates, and months to surveillance.
HPs <1 cm in rectosigmoid colon or <5 mm and proximal to sigmoid colon.
To further examine the risk for high-risk adenomas, relative to the serrated groups, we repeated the models with high-risk adenoma as the reference group. We observed that individuals with only 5- to 9-mm HPs had an elevated risk for metachronous large SPs (OR, 2.50; 95% CI, 1.34–4.68) as compared with those with high-risk adenomas. The highest risk was observed in those with large HPs, SSPs, or TSAs (OR, 4.01; 95% CI, 2.62–6.14). However, those with only nonsignificant HPs did not have an elevated risk (OR, 1.12; 95% CI, .70–1.80) (data not shown). Conversely, high-risk conventional adenomas with no SPs at index were predictive of metachronous advanced neoplasia (OR, 2.05; 95% CI, 1.55–2.70). The covariates for the models in Table 2 are shown in Table 3.
TABLE 3.
Covariates for logistic regression models in Table2
| Sex, female vs male | 1.23 (.93–1.62) | ..80 (.66–.98) |
| Age (continuous) | .99 (.97–1.00) | 1.03 (1.01–1.04) |
| Body mass index (continuous) | .99 (.97–1.02) | 1.03 (1.01–1.04) |
| Family history (first-degree relative) | .79 (.56–1.11) | 1.07 (.86–1.33) |
| Previous colorectal neoplasia | 1.53 (1.13–2.06) | 1.07 (.87–1.32) |
| Smoking | ||
| Never | 1.0 (ref) | 1.0 (ref) |
| Past | 1.05 (.76–1.44) | 1.07 (.87–1.32) |
| Current | 1.98 (1.37–2.87) | 1.36 (1.00–1.86) |
| Year of index | 1.06 (1.00–1.12) | .96 (.93–1.00) |
| Month since index exam (>54) | .84 (.59–1.19) | .85 (.68–1.07) |
| Clinically significant serrated polyp for endoscopist on index (≥ vs <7%) | .93 (.68–1.27) | 1.10 (.88–1.38) |
| Clinically significant serrated polyp for endoscopist on follow-up (≥ vs <7%) | 1.56 (1.13–2.16) | 1.24 (1.00–1.54) |
Values are odds ratio (95% confidence interval).
To examine the impact of synchronous adenomas in the SP group, we conducted an additional analysis that excluded those individuals with synchronous adenomas from the 3 SP groups. The results were not significantly changed with regard to risk for large SPs; individuals with 5- to 9-mm HPs and those with large HPs or any SSP or TSAs were at higher risk. In this sample with synchronous adenomas removed from the SP groups, the highest risk for metachronous advanced neoplasia was observed for the high-risk adenoma group (OR, 2.92; 95% CI, 1.99–4.29). Conversely, individuals with 5- to 9-mm proximal HPs who had an increased risk of metachronous advanced neoplasia in the total sample (Table 2) were no longer at increased risk when those individuals with synchronous adenomas were excluded (OR, 1.50; 95% CI, .74–3.04). These data are shown in Table 4 (risks for metachronous large SPs and metachronous advanced neoplasia).
TABLE 4.
Risk for metachronous large (≥1 cm) SPs on surveillance examination in individuals with index 5- to 9-mm proximal HPs as compared with other index findings in subanalysis in which individuals with adenomas excluded from serrated groups
| Metachronous risk large SPs | Metachronous risk AAs | ||||||
|---|---|---|---|---|---|---|---|
| Large (≥1 cm) HPs or any SSP/TSA (no adenomas) | 630 | 11.7% (74) | 10.36 (6.35–16.92) | Large (≥ 1 cm) HPs or any SSP/TSA (no adenomas) | 630 | 2.5% (16) | 0.72 (.38–1.38) |
| 5- to 9-mm proximal HP (no adenomas) | 209 | 4.8% (10) | 4.92 (2.24–10.77) | 5- to 9-mm proximal HP (no adenomas) | 209 | 4.8% (10) | 1.50 (.74–3.04) |
| Nonsignificant HPs† (no adenomas) | 1372 | 1.7% (24) | 1.94 (1.10–3.43) | Nonsignificant HPs† (no adenomas) | 1372 | 3.2% (44) | 1.0 (reference) |
| Low-risk adenomas (no SPs) | 2962 | 1.0% (30) | 1.0 (reference) | Low-risk adenomas (no SPs) | 2962 | 4.3% (127) | 1.43 (1.00–2.04) |
| High-risk adenomas (no SPs) | 1635 | 2.0% (33) | 1.71 (.98–2.99) | High-risk adenomas (no SPs) | 1635 | 9.7% (158) | 2.92 (1.99–4.29) |
Values are % (n) unless otherwise defined.
AA, Advanced adenoma; HP, hyperplastic polyp; SP, serrated polyp; SSP, sessile serrated polyp; TSA, traditional serrated adenoma.
Adjusted for age, sex, body mass index, previous neoplasia, smoking, family history of colorectal cancer, clinically significant SP detection rates, and months to surveillance.
HPs <1 cm in rectosigmoid colon or <5 mm and proximal to sigmoid colon.
When examining the number of 5- to 9-mm HPs at index examination, we observed no significant difference in risks between those with 1 to 2 versus 3 or more proximal HPs 5 to 9 mm and the risk of metachronous large SPs (14/293 [4.8%] vs 4/83 [4.8%], respectively; P = 1.0) or metachronous advanced neoplasia (25/293 [8.5%] vs 5/83 [6.0%], respectively; P =.46). Of the 5 individuals at index who could be classified as having serrated polyposis syndrome, 1 had a large SP at surveillance examination.
To minimize the impact of missed SPs as opposed to measuring new polyps being detected at surveillance examination, we restricted our analysis to examinations performed at least 36 months after index. The mean follow-up in this sample was 61.4 ± 20.7 months. We observed no significant change in the results (Table 5).
TABLE 5.
Risk for metachronous large (≥1 cm) SPs on surveillance examination for individuals with 5- to 9-mm proximal HPs at index examination as compared with other index findings, restricted to subsequent colonoscopy performed 36 months or more after index examination
| Metachronous risk of large SPs at ≥36 months after index colonoscopy | ||||
|---|---|---|---|---|
| Large (≥ 1 cm) HPs or any SSP/TSA | 715 | 51.0 ± 17.7 | 7.0 (50) | 5.98 (3.54–10.11) |
| 5- to 9-mm proximal HP | 304 | 62.7 ± 16.2 | 4.9 (15) | 5.74 (2.94–11.19) |
| Nonsignificant HPs† | 2128 | 66.9 ± 24.2 | 2.1 (45) | 2.20 (1.32–3.65) |
| High-risk adenomas (no SPs) | 1048 | 52.5 ± 18.0 | 2.2 (23) | 2.08 (1.14–3.81) |
| Low-risk adenomas (no SPs) | 2702 | 67.9 ± 23.9 | 1.0 (27) | 1.0 (reference) |
Values are % (n) unless otherwise defined.
AA, Advanced adenoma; HP, hyperplastic polyp; SP, serrated polyp; SSP, sessile serrated polyp; TSA, traditional serrated adenoma.
Adjusted for age, sex, body mass index, previous neoplasia, smoking, family history of colorectal cancer, endoscopist clinically significant SP detection rates, and months to surveillance.
HPs <1 cm in rectosigmoid colon or <5 mm and proximal to sigmoid colon.
DISCUSSION
We observed that, similar to the risk of metachronous lesions for individuals with large HPs, SSPs, or TSAs at index examination, adults with 5- to 9-mm HPs proximal to the sigmoid colon at index colonoscopy were at increased risk for metachronous large SPs as compared with individuals with conventional adenomas and no SPs at index colonoscopy. Although individuals with high-risk adenomas and nonsignificant HPs on index had an elevated risk for metachronous large SPs as compared with the low-risk adenoma group, the risks for these 2 groups were significantly lower as compared with individuals with large HPs or any SSP/TSA or 5- to 9-mm HPs. The increased risk for these 2 serrated groups persisted after we excluded those individuals with index SPs who had synchronous adenomas. Thus, the risk for metachronous large SPs was also not influenced by the presence of synchronous conventional adenomas on index examination. In addition, the number of 5- to 9-mm proximal HPs did not alter the risk for metachronous large SPs.
This analysis provides important evidence to inform best practice for the surveillance of adults with SPs, especially those with proximal 5- to 9-mm HPs. Several long-term studies have found an increased risk for CRC in patients with large HPs, SSPs, or TSAs,3,6–8 and guidelines appropriately suggest close surveillance intervals for patients with these lesions.4 Although limited data exist regarding the clinical significance of 5- to 9-mm HPs proximal to the sigmoid colon, an expert panel has recommended 5-year follow-up for patients with these lesions.2 However, the recent USMSTF for CRC has highlighted the lack of data regarding metachronous risk for individuals with proximal 5- to 9-mm HPs.5 As noted above, studies that have reassessed the pathology of HPs have observed that many 5- to 9-mm HPs may actually be SSPs, further supporting the importance of understanding the metachronous risk posed by these polyps.9,10
Among studies examining the risk of index SPs,12–14,17,18 our data are the first to examine 5- to 9-mm proximal HPs. A few prior studies examined the metachronous risk for small index SSPs but did not include small HPs in their analyses.13,17 Some studies have lacked sufficient power to examine metachronous risk of index SPs because they are less common than conventional adenomas.12,18 The large long-term database of the NHCR allowed patients to be stratified by histology, size, and location of index serrated lesions, providing adequate numbers to examine the relative risk for significant future polyps in patients with 5- to 9-mm proximal HPs as compared with other SPs and conventional adenomas.
In addition, our large database allowed us to separate the outcomes of advanced neoplasia and large SPs. Although the metachronous outcome of interest after conventional adenomas is advanced neoplasia, published studies have shown that individuals with only index SPs do not have an increased risk for these conventional adenomas,11,12,14 supporting the idea of 2 pathways to CRC and suggesting that assessing the risk for metachronous large SPs would be more informative in individuals with index SPs.11,12,19,20 This separation of outcomes was essential to clarifying specific risks that are harder to distinguish in studies that use a combined conventional adenoma and SP outcome. Furthermore, we were able to conduct a subanalysis that included only those individuals with SPs and no synchronous conventional adenomas. We observed no significant change in our results, further supporting the concept that 5- to 9-mm proximal HPs alone confer an increased future risk of large SPs. Other strengths of our analysis include the incorporation of several important risk factors for conventional adenomas, SPs, and CRC, such as smoking and BMI.11,21–28 We did observe that current smoking was associated with a 2-fold increased risk for metachronous large SPs. In addition, we assessed future risks for all index groups, including patients with only conventional low- or high-risk adenomas, thus providing relative risks for all individuals who may undergo surveillance after colonoscopy.
There are several potential limitations. First, our data are from a single state. However, although New Hampshire lacks significant racial diversity, our population includes substantial ethnic, socioeconomic, and rural/urban diversity.29 It will be helpful to assess these results in other more racially diverse settings. Second, the location of polyps, which was important in our classification of some SPs, may be subject to misclassification. Third, endoscopists may place more than 1 polyp in a jar. However, NHCR pathology abstractors carefully match each specimen recorded on the pathology report to an individual polyp identified by the endoscopist on the NHCR procedure form, using location, size, and number to support the most accurate assignment of polyp histology possible.15 In addition, we stratified groups by the most advanced pathology in the colon, minimizing the potential impact of pooling of polyps on this analysis. Fourth, our categories are based on endoscopist estimate of size, which can have interobserver variability.30 Finally, although we included year of diagnosis as well as CSSP detection rates in our model and we observed similar results when restricting our analysis to examinations performed at least 36 months after index examination, we acknowledge that missed polyps at index could be a confounding factor.
In summary, we observed that 5- to 9-mm HPs proximal to the sigmoid colon on index examination were associated with an increased risk for future large SPs, whereas nonsignificant HPs were associated with a lower risk. These data provide strong evidence to support shorter surveillance intervals for individuals with 5- to 9-mm proximal HPs than for patients with only nonsignificant HPs. An expert panel has recommended 5-year follow-up for individuals with these lesions.2 Our outcome of metachronous large SPs, although supported by other studies, should still be validated in other populations to clarify the appropriate follow-up for individuals with index SPs.
DISCLOSURE:
All authors disclosed no financial relationships. Research support for this study was provided by American Society for Gastrointestinal Endoscopy 2018 Endoscopic Research Award (grant nos. R01CA131141, 1R21CA191651-01A1), the National Cancer Institute (contract no. HHSN261201400595P), and the Norris Cotton Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
Abbreviations:
- AA
advanced adenoma
- BMI
body mass index
- CRC
colorectal cancer
- CSSP
clinically significant serrated polyp
- HP
hyperplastic polyp
- NHCR
New Hampshire Colonoscopy Registry
- SP
serrated polyp
- SSP
sessile serrated polyp
- TSA
traditional serrated adenoma
- USMSTF
U.S. Multi-Society Task Force
REFERENCES
- 1.Lindholm CR, Anderson JC, Srivastava A. The dark side of the colon: current issues surrounding the significance, prevalence, detection, diagnosis and management of serrated polyps. Curr Opin Gastroenterol 2019;35:34–41. [DOI] [PubMed] [Google Scholar]
- 2.Rex DK, Ahnen DJ, Baron JA, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012;107:1315–29; quiz 1314, 1330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Erichsen R, Baron JA, Hamilton-Dutoit SJ, et al. Increased risk of colorectal cancer development among patients with serrated polyps. Gastroenterology 2016;150:895–902. [DOI] [PubMed] [Google Scholar]
- 4.Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844–57. [DOI] [PubMed] [Google Scholar]
- 5.Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on colorectal cancer. Gastrointest Endosc 2020;91:463–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.He X, Hang D, Wu K, et al. Long-term risk of colorectal cancer after removal of conventional adenomas and serrated polyps. Gastroenterology 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Holme O, Bretthauer M, Eide TJ, et al. Long-term risk of colorectal cancer in individuals with serrated polyps. Gut 2015;64:929–36. [DOI] [PubMed] [Google Scholar]
- 8.Hiraoka S, Kato J, Fujiki S, et al. The presence of large serrated polyps increases risk for colorectal cancer. Gastroenterology 2010;139: 1503–10. [DOI] [PubMed] [Google Scholar]
- 9.Anderson JC, Lisovsky M, Greene MA, et al. Factors associated with classification of hyperplastic polyps as sessile serrated adenomas/polyps on morphologic review. J Clin Gastroenterol 2018;52:524–9. [DOI] [PubMed] [Google Scholar]
- 10.Singh H, Bay D, Ip S, et al. Pathological reassessment of hyperplastic colon polyps in a city-wide pathology practice: implications for polyp surveillance recommendations. Gastrointest Endosc 2012;76:1003–8. [DOI] [PubMed] [Google Scholar]
- 11.Anderson JC, Butterly LF, Robinson CM, et al. Risk of metachronous high-risk adenomas and large serrated polyps in individuals with serrated polyps on index colonoscopy: data from the New Hampshire Colonoscopy Registry. Gastroenterology 2018;154:117–27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Macaron C, Vu HT, Lopez R, et al. Risk of metachronous polyps in individuals with serrated polyps. Dis Colon Rectum 2015;58:762–8. [DOI] [PubMed] [Google Scholar]
- 13.Symonds E, Anwar S, Young G, et al. Sessile serrated polyps with synchronous conventional adenomas increase risk of future advanced neoplasia. Dig Dis Sci 2019;64:1680–5. [DOI] [PubMed] [Google Scholar]
- 14.Burnett-Hartman AN, Chubak J, Hua X, et al. The association between colorectal sessile serrated adenomas/polyps and subsequent advanced colorectal neoplasia. Cancer Causes Control 2019;30:979–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Greene MA, Butterly LF, Goodrich M, et al. Matching colonoscopy and pathology data in population-based registries: development of a novel algorithm and the initial experience of the New Hampshire Colonoscopy Registry. Gastrointest Endosc 2011;74:334–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Anderson JC, Butterly LF, Weiss JE, et al. Providing data for serrated polyp detection rate benchmarks: an analysis of the New Hampshire Colonoscopy Registry. Gastrointest Endosc 2017;85:1188–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Melson J, Ma K, Arshad S, et al. Presence of small sessile serrated polyps increases rate of advanced neoplasia upon surveillance compared with isolated low-risk tubular adenomas. Gastrointest Endosc 2016;84:307–14. [DOI] [PubMed] [Google Scholar]
- 18.Pereyra L, Zamora R, Gomez EJ, et al. Risk of metachronous advanced neoplastic lesions in patients with sporadic sessile serrated adenomas undergoing colonoscopic surveillance. Am J Gastroenterol 2016;111: 871–8. [DOI] [PubMed] [Google Scholar]
- 19.Bensen SP, Cole BF, Mott LA, et al. Colorectal hyperplastic polyps and risk of recurrence of adenomas and hyperplastic polyps. Polyps Prevention Study. Lancet 1999;354:1873–4. [DOI] [PubMed] [Google Scholar]
- 20.Laiyemo AO, Murphy G, Sansbury LB, et al. Hyperplastic polyps and the risk of adenoma recurrence in the polyp prevention trial. Clin Gastroenterol Hepatol 2009;7:192–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Anderson JC, Attam R, Alpern Z, et al. Prevalence of colorectal neoplasia in smokers. Am J Gastroenterol 2003;98:2777–83. [DOI] [PubMed] [Google Scholar]
- 22.Anderson JC, Latreille M, Messina C, et al. Smokers as a high-risk group: data from a screening population. J Clin Gastroenterol 2009;43:747–52. [DOI] [PubMed] [Google Scholar]
- 23.Anderson JC, Messina CR, Dakhllalah F, et al. Body mass index: a marker for significant colorectal neoplasia in a screening population. J Clin Gastroenterol 2007;41:285–90. [DOI] [PubMed] [Google Scholar]
- 24.Anderson JC, Fortinsky RH, Kleppinger A, et al. Predictors of compliance with free endoscopic colorectal cancer screening in uninsured adults. J Gen Intern Med 2011;26:875–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Anderson JC, Rangasamy P, Rustagi T, et al. Risk factors for sessile serrated adenomas. J Clin Gastroenterol 2011;45:694–9. [DOI] [PubMed] [Google Scholar]
- 26.Anderson JC, Stein B, Kahi CJ, et al. Association of smoking and flat adenomas: results from an asymptomatic population screened with a high-definition colonoscope. Gastrointest Endosc 2010;71:1234–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.He X, Wu K, Ogino S, et al. Association between risk factors for colorectal cancer and risk of serrated polyps and conventional adenomas. Gastroenterology 2018;155:355–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Anderson JC, Weiss JE, Robinson CM, et al. Adenoma detection rates for screening colonoscopies in smokers and obese adults: data from the New Hampshire Colonoscopy Registry. J Clin Gastroenterol 2017;51:e95–100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Rice K, Sharma K, Li C, et al. Cost-effectiveness of a patient navigation intervention to increase colonoscopy screening among low-income adults in New Hampshire. Cancer 2019;125:601–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Anderson BW, Smyrk TC, Anderson KS, et al. Endoscopic overestimation of colorectal polyp size. Gastrointest Endosc 2016;83:201–8. [DOI] [PubMed] [Google Scholar]