Abstract
Patients with serrated polyposis develop multiple colorectal hyperplastic and/or serrated sessile adenomas/polyps. We investigated the risk of colorectal and other cancers by analyzing data from 64 patients with serrated polyposis (mean age at diagnosis, 54 y; 41% male; 92% white) listed in the Johns Hopkins Polyposis Registry. Medical, endoscopic, and histopathology reports were evaluated. Six patients (9.4%) had a history of colorectal cancer, diagnosed at a mean age of 56 y; 6 additional patients (9.4%) had at least 1 advanced colorectal adenoma. Extra-colonic cancers were found in 16% of the study population. The standard incidence ratio for colorectal cancer in patients with serrated polyposis was 18.72 (95% confidence interval, 6.87 – 40.74) and for extra-colonic cancer was 31.20 (95% confidence interval, 14.96 – 57.37), compared to the SEER population. Patients with serrated polyposis therefore have a high risk for colorectal cancer and require vigilant colorectal surveillance, starting at the time of diagnosis of serrated polyposis. The risk of extra-colonic cancer also appears to be increased, but this requires further evaluation.
Keywords: hyperplastic polyps, sessile polyps, premalignant, colon cancer
INTRODUCTION
Serrated polyposis (SP) is a disorder typically characterized by several dozen serrated polyps distributed throughout the colorectum. Also, these patients can have synchronous colorectal adenomas (1,2).
SP has been associated with an increased risk of colorectal cancer. Evidence for this concept comes from a limited collection of case reports providing variable estimates of colorectal cancer risk (3–8). The risk of extra-colonic malignancies in SP has not been well examined. This study reports colorectal and extra-colonic cancers in a cohort of SP patients.
METHODS
Study population
Patients with SP enrolled in the Johns Hopkins Registry between January 1, 2001 and October 1, 2012. These patients self-enrolled in the Registry without physician referral or were enrolled by a Hopkins physician who saw the patient. None were referred to the Registry because of a history of cancers or a family history of SP. Patients met the WHO criteria for SP with: I) at least 5 serrated polyps proximal to the sigmoid colon with 2 or more of these being >10mm; or II) any number of serrated polyps proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis; or III) >20 serrated polyps of any size but distributed throughout the colon (2).
Study design
Data were collected from medical records and histopathology reports. All cancers were confirmed by pathology report. Patients with advanced adenomas (an adenoma 1 cm or greater, with villous components, or with high-grade dysplasia) were identified. A risk assessment for colorectal adenocarcinoma and extra-colonic cancer risk was performed. The standardized incidence ratio (SIR) was estimated using the Indirect Method, with observed cancer incidence among patients with SP divided by the expected cancer incidence based on the SEER population rates (2000–2011) (9). SIR values were estimated by sex and type of cancer: colorectal cancer and extra-colonic cancer. SIR values derived from the comparison with SEER data were adjusted for age, but not sex.
RESULTS
The study population was 64 patients with SP from 62 pedigrees (Table 1). The mean age (SD) at diagnosis of SP was 53.6+11.5 yrs.
Table 1.
Characteristics of Study Patients
| No. of patients | 64 |
|
| |
| Sex – no. (%) | |
| Female | 38 (59) |
| Male | 26 (41) |
|
| |
| Caucasian race: no. (%) | 59 (92) |
| African American | 5 (8) |
|
| |
| No. of pedigrees | 62 |
|
| |
| Serrated polyposis mean age at diagnosis- yr. Mean+SD (range) |
53.6+11.2 (22–78) |
|
| |
| No. (%) fulfilling WHO criteria for SPS | |
| I | 17 (27) |
| II | 0 (0) |
| III | 47 (73) |
|
| |
| Colorectal cancer mean age at diagnosis- yr. Mean+SD (range) |
56.0+13.0 (45–78) |
Patients with SP who developed colorectal and extra-colonic cancer are listed in Table 2. Six of 64 patients (9.4%) with SP developed colorectal cancer. The mean age of diagnosis of colorectal cancer was 56.0+13.0 (45–75). An additional 6 patients had advanced adenomas at a mean age of 57.17+10.8 (43–69). Sixteen percent of the study population developed an extra-colonic cancer (Table 2).
Table 2.
Patients with serrated polyposis who developed cancer
| Age at diagnosis of cancer | Sex | Race | Cancer type |
|---|---|---|---|
| 30 | male | White/Caucasian | Basal cell carcinoma |
| 40 | female | White/Caucasian | Breast |
| 49 | female | White/Caucasian | Breast |
| 60 | female | White/Caucasian | Breast |
| 35 | female | White/Caucasian | Cervix |
| 45 | female | White/Caucasian | Colorectal (sigmoid) |
| 47 | female | White/Caucasian | Colorectal (sigmoid) |
| 47 | male | White/Caucasian | Colorectal (sigmoid) |
| 50 | male | White/Caucasian | Colorectal (cecum) |
| 69 | female | White/Caucasian | Colorectal (sigmoid) |
| 75 | female | White/Caucasian | Colorectal (ascending) |
| 24 | female | White/Caucasian | Hodgkins Lymphoma |
| 50 | female | White/Caucasian | Ovarian |
| 53 | male | White/Caucasian | Prostate |
| 56 | male | African American | Prostate |
| 53 | male | African American | Ureter |
The SIR (95% CI) of colorectal cancer in patients with SP was 26.28 (7.16 – 67.29) for females, 11.72 (1.42 – 42.32) for males, and 18.72 (6.87 – 40.74) overall. The SIR (95% CI) for extra-colonic cancer in patients with SP was 39.42 (14.47 – 85.80) for females, 23.43 (6.38 – 59.99) for males, and 31.20 (14.96 – 57.37) overall.
DISCUSSION
Literature review reveals a large range, 7% to 70%, of risk of colorectal cancer in SP patients (1,3–8,10). In the 3 largest case series of patients with SP, a high percentage of patients (26% to 28.5%) were diagnosed with colorectal cancer (1,10,11). All published reports of SP found 122 of 308 patients (39.6%) diagnosed with CRC (12). Our study reports a high risk of colorectal cancer and advanced adenomas in SP. Overall SP patients had elevated SIR (19.01) of CRC with the risks greater for females than males. These high-risk estimates for CRC are consistent with the high rate of adenomas and sessile serrated adenomas/polyps found on initial colonoscopy evaluation (13). Also, Boparai et al. calculated a worrisome risk of colorectal cancer during surveillance of 7% at 5 years in those with intact colons (10).
In SP the increased risk of colorectal cancer appears associated with younger age of diagnosis. In our study, the average age of diagnosis of colorectal cancer was 56. Literature review of the three largest case series reveals a median age of colorectal cancer of 45, 56, and mean age of 63. All three studies reported patients diagnosed with CRC in the 4th decade of life (1,10,11).
Kalady et al., suggested 3 different phenotypes of serrated polyposis (11). These include patients with few large right-sided polyps, those with many small left sided polyps, and individuals with a combination of left- and right-sided polyps. Although differences in CRC risk could be associated with phenotype, the frequency of colorectal cancer noted by this investigator in these 3 types was similar (21–28%). The majority (77%) of patients in our cohort fulfill the third of the WHO criteria. Small numbers of observations made assessment of CRC risk by phenotype impossible.
Elevated risk of extra-colonic tumors is commonly noted in polyposis syndromes. Kalady et al. found that 28% of serrated polyposis patients had extra-colonic cancer (11). Also, 54% of patients had a family history of extra-colonic cancer. Jasperson et al. (14) found 24% of SP patients had extra-colonic cancer, although Hazewhinkel et al. (15) reported a relative risk of 0.69 (95% Cl 0.36–1.33) for extra-colonic cancers. In our study, 16% had extra-colonic cancer. Risk assessment showed an elevated risk for extra-colonic cancer in SP patients (SIR, 31.2) with the risks greater for females than males.
A caution raised when comparing a registry-based population to the general US population is detection bias meaning that surveillance of the population in the registry may lead to higher diagnosis of certain disorders compared to the general population. This concern cannot be discounted. Another limitation in interpretation of the results is that the small number of patients in the study causes large confidence intervals in the estimates of cancer risk.
This study, with other literature, argues for a high risk of colorectal cancer in patients with SP. These findings support at least initial annual colonoscopy surveillance in patients with intact colons and similar endoscopic evaluation in those with colectomy and retained colorectal segments with removal of all polyps at the time of examination. These recommendations are consistent with experts who promote close surveillance in patients treated endoscopically for SP (16). The NCCN guidelines recommend colonoscopy surveillance for serrated polyposis patients with intact colons every 1–3 years depending on the number of polyps found and cleared at colonoscopy (17). Young and Parry (18), recommend surgery when polyps cannot be controlled endoscopically, particularly if adenomatous features are present.
Acknowledgments
We are indebted to Ms. Linda Welch for technical support.
Supported in part by the John G Rangos Sr Charitable Foundation; The Clayton Fund; and NIH grants P50 CA 62924-17, CA096297, CA096300, U54MD 007587.
Abbreviations
- SP
serrated polyposis
- CRC
colorectal cancer
- RR
relative risk
- NCCN
National Comprehensive Cancer Network
Footnotes
Author Contributions:
Edelstein - A. B. C. D E. F. G. H., Cruz-Correa - B. E. F. G. H., Soto-Salgado- B. E. F. G. H. Axilbund - C. D. G. H., Hylind - C. D. G. H., Romans - C. D. G. H., Blair – D. G. H., Wiley – D. G. H, Tersmette- A. B. C. D E. F. G. H, Offerhaus- A. B. C. D E. F. G. H., Giardiello - A. B. C. D E. F. G. H.
A: literature search, B: figures, C: study design, D: data collection, E: data analysis, F: data interpretation, G: writing, H: critical revision of the manuscript for important intellectual content
Disclosures: The authors have no conflicts to disclose
Conflict of Interest Statement: No conflicts of interest exist.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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