Clinical Roundtable Monograph Gastroenterology & Hepatology August 2018 Incomplete Resection Rates in Polyps Smaller Than 2 Centimeters Proceedings From a Live Clinical Roundtable Held During Digestive Disease Week • June 2-5, 2018 • Washington, DC Moderator David A. Johnson, MD Professor of Medicine Chief of Gastroenterology Eastern VA Medical School Norfolk, Virginia Discussants Michael B. Wallace, MD, MPH Professor of Medicine Mayo Clinic Jacksonville, Florida Vivek Kaul, MD, FACG, FASGE, AGAF Segal-Watson Professor of Medicine Chief, Division of Gastroenterology & Hepatology Center for Advanced Therapeutic Endoscopy University of Rochester Medical Center Rochester, New York Tonya Kaltenbach, MD, MS Associate Professor of Clinical Medicine University of California, San Francisco San Francisco, California Abstract: Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in the United States. Colonoscopy is the most effective strategy for preventing CRC. Although the benchmark of colonoscopy performance, the adenoma detection rate, clearly correlates with prevention of interval cancers and CRC-related death, it is clear that polyp (adenoma) detection is not enough. Adequate and complete resection of the adenoma is imperative to ensure effective CRC prevention. Polyp size is the primary risk factor for malignancy; in general, the bigger the polyp, the greater the risk for malignancy. This monograph, however, focuses on strategies to improve the incomplete resection rate for polyps smaller than 2 cm, as these represent the vast majority of polyps encountered in clinical practice. Selection of the polypectomy technique depends on the size and type of polyp. In general, cold forceps biopsy is used for polyps smaller than 4 mm, cold snare polypectomy is used for polyps 4 to 10 mm, and hot snare polypectomy and endoscopic mucosal resection (EMR) are highly effective for larger polyps. The combined use of submucosal lifting and snare, as is performed with EMR, allows full resection of virtually all lesions of any size. Typically, EMR begins with a submucosal injection to create vertical lift. The submucosal lift is one of the most significant advances in complete polyp removal. It is used with the goals of improving visualization of polyp margins, capturing the entire polyp, and facilitating safe and complete resection. Several solutions have been used to achieve a submucosal lift. Only one solution, Eleview, is approved by the US Food and Drug Administration for this procedure. In a clinical trial, Eleview decreased the mean total injected volume and the mean total injected volume per lesion as compared with saline. Proper application of the submucosal solution is imperative to optimize outcomes with EMR. Supported through funding from Aries Pharmaceuticals Inc. CLINICAL ROUNDTABLE MONOGRAPH Incomplete Resection Rates: Current Trends and Clinical Consequences David A. Johnson, MD Professor of Medicine Chief of Gastroenterology Eastern VA Medical School Norfolk, Virginia here is growing recognition that adenoma showed the alarming prevalence of incomplete resection. detection is the key aspect in terms of prevent- There is a disconnect between high adenoma detec- ing colorectal cancer (CRC) and CRC-related tion rates (ADRs), which should be associated with risk Tdeath. Polyp detection, however, is just the beginning. reduction and prevention of CRC and cancer-related The paradigm begins with the effective identification deaths, and the polypectomy technique and adequacy of and complete resection of polyps, which leads to cancer resection. Although historically colonoscopy performance prevention. Additionally, it is not enough that just a single has been predicated on adenoma detection, it is detection polyp is resected, but complete resection of all adenomas combined with adequate resection that improves clinical is imperative to achieve optimal CRC prevention. outcomes and consequences. Complete resection of all adenomas is challenging, as was demonstrated in the CARE study (Complete Adenoma Detection Rate and Colonoscopy Adenoma Resection).1 This study analyzed 346 neo- The ADR is recognized as the lead benchmark for assess- plastic polyps from 269 patients that were removed by ing colonoscopy quality and thereby optimizing CRC 11 gastroenterologists. Biopsy evaluation showed that prevention. The ADR is defined as the percentage of 10.1% of these polyps were incompletely resected. This patients at average risk for CRC who are found to have incomplete resection rate (IRR) increased with polyp at least 1 adenoma or adenocarcinoma during a screen- size. For example, the IRR was significantly higher for ing colonoscopy.2 The ADR applies to individuals with large polyps that were 10 mm to 20 mm vs small polyps an average risk for developing CRC, and it is limited to that were 5 mm to 9 mm (17.3% vs 6.8%; relative risk, the first screening colonoscopy. It refers to the detection 2.1). Another factor that impacted IRR was the polyp of conventional adenomas and carcinomas; importantly, type. The IRR was higher in sessile serrated adenomas/ it does not encompass detection of sessile serrated polyps. polyps than conventional adenomas (31.0% vs 7.2%; With these limitations to consider, why is the ADR relative risk, 3.7). Notably, the clinical experience of the important? There is a clear association between a higher endoscopist did not correspond to the IRR. The IRR for ADR and lower rates of interval cancers, advanced can- endoscopists with at least 20 polypectomies ranged from cers, and fatal cancers. An increase in ADR corresponds 6.5% to 22.7%. There was a 3.4-fold difference between to a decrease in the incidence of CRC and cancer-related the highest and lowest IRR after adjusting for size and death (Figure 1).2 Even small, incremental differences sessile serrated histology. Thus, the CARE study clearly in the ADR have an important effect on cancer preven- Indexed through the National Library of Medicine (PubMed/Medline), PubMed Central (PMC), and EMBASE Disclaimer Funding for this monograph has been provided by Aries Pharmaceuticals Inc. Support of this monograph does not imply the sup- porter’s agreement with the views expressed herein. Every effort has been made to ensure that drug usage and other information are presented accurately; however, the ultimate responsibility rests with the prescribing physician. Gastro-Hep Communications, Inc., the supporter, and the participants shall not be held responsible for errors or for any consequences arising from the use of information contained herein. Readers are strongly urged to consult any relevant primary literature. No claims or endorsements are made for any drug or compound at present under clinical investigation. ©2018 Gastro-Hep Communications, Inc. 611 Broadway, Suite 310, New York, NY 10012. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form. 2 Gastroenterology & Hepatology Volume 14, Issue 8, Supplement 5 August 2018 INCOMPLETE RESECTION RATES IN POLYPS SMALLER THAN 2 CENTIMETERS Figure 1. An ADR of 20% 0.0020 or higher was associated ADR <11.0% with a reduced rate of ADR 11.0-14.9% interval cancers in a Polish 0.0015 colonoscopy screening ADR 15.0-19.9% program. ADR, adenoma ADR ≥20.0% detection rate. Adapted 0.0010 from Kaminski MF et al. Quality indicators for 0.0005 colonoscopy and the risk of interval cancer. N Engl Cumulative Hazard Rate Hazard Cumulative J Med. 2010;362(19): 0.0000 1795-1803.2 0 12 24 36 48 60 Number at Risk Months ADR <11.0% 15,883 15,805 15,744 15,669 9355 4717 ADR 11.0-14.9% 13,281 13,223 13,182 13,120 7571 4003 ADR 15.0-19.9% 6607 6582 6562 6539 4022 2529 ADR ≥20.0% 9255 9235 9202 9166 7155 5548 tion. For example, in a study that evaluated 314,872 P=.035) for cancer-related deaths. The adjusted hazard colonoscopies performed by 136 gastroenterologists, the ratios for interval CRCs decreased to 0.27 (95% CI, 0.12- ADRs ranged from 7.4% to 52.5%.3 Each 1.0% increase 0.63; P=.003) when the highest-quintile ADR category in the ADR was associated with a 3.0% decrease in the was reached and to 0.18 (95% CI, 0.06-0.56; P=.003) risk of cancer (hazard ratio, 0.97; 95% CI, 0.96-0.98). when the highest category was maintained. During the follow-up period of this study, 712 interval colorectal adenocarcinomas and 147 deaths from interval Incomplete Resection Rates and Clinical CRC were identified. When the ADRs were grouped Implications into quintiles, the unadjusted risk for interval cancer Colonoscopy has a miss rate of approximately 17% for was highest in the lowest ADR quintile (9.8 cases per larger polyps (≥10 mm).5,6 Interval cancers (with rare 10,000 person-years). This unadjusted risk for interval exceptions, such as hereditary syndrome cancers) indicate cancer decreased with each subsequently increasing ADR that the endoscopist missed lesions or did not completely quintile (8.6, 8.0, 7.0, and 4.8 cases per 10,000 person- remove them during the baseline examination (regardless years). When the patients of endoscopists who had ADRs of whether the examination was for screening or surveil- segregated to the highest quintile were compared with lance). Missed lesions reflect the quality of the examina- patients of endoscopists with ADRs in the lowest quintile, tion. In an analysis of the Polyp Prevention Trial, which the adjusted hazard ratio for any interval cancer was 0.52 included 2079 patients, 13 had cancer detected through- (95% CI, 0.39-0.69). Similarly, the adjusted hazard ratio out 5810 person-years of observation.7 Among these 13 was 0.43 (95% CI, 0.29-0.64) for advanced-stage interval cases, 7 (53.8%) were a potentially “avoidable” cancer or cancers and 0.38 (95% CI, 0.22-0.65) for fatal interval one detectable at an earlier time interval owing to either cancers.