COLONOSCOPY QUALITY: FROM ASSESSMENT TO IMPLEMENTATION Charles J. Kahi, MD, MSc Richard L. Roudebush VA Medical Center Indiana University School of Medicine Indianapolis, Indiana INSGNA Fall Conference September 12th, 2015

NONE DISCLOSURE Speaker Relationship with Industry, including Consultant Speaker Ownership/ Partnership Principal Research Institutional, Organizational or Other Financial Benefit: NONE

OBJECTIVES Review protective effect of colonoscopy against CRC Review factors associated with interval cancers Discuss colonoscopy quality measures, with emphasis on the ADR Present overview of serrated polyps Discuss implementation and effect of quality interventions.

COLORECTAL CANCER IN THE US Third most common cancer and second most common cause of cancer deaths 2015 estimates: 132,700 new cases 49,700 deaths Siegel et al. CA Cancer J Clin 2015; 65: 5-29.

Colonoscopy prevents CRC National Polyp Study - 76% to 90% reduction in CRC incidence compared to 3 reference populations - 5 cancers found, 20.7 expected (SEER) - Incidence ratio: 0.24 (95% CI: 0.08-0.56, p<0.001) - Long-term follow-up: Sustained impact on CRC mortality (53% reduction in CRC deaths after mean 16 years) Winawer et al. NEJM 1993; 329: 1977-1981 Zauber et al. NEJM 2012;366:687-96.

Lower Protection in the Right Colon Author, year Outcome Overall CRC (95% CI) Left-sided CRC (95% CI) Right-sided CRC Baxter, 2009 Ontario, Canada CRC Mortality (OR) 0.63 (0.57-0.69) 0.33 (0.28-0.39) 0.99 (0.86-1.14) Singh, 2010 Manitoba, Canada (SMR) 0.71 (0.61-0.82) 0.53 (0.42-0.67) 0.94 (0.77-1.17) Brenner, 2011 Rhine-Neckar, Germany CRC Incidence 0.23 (0.19-0.27) 0.16 (0.12- 0.20) 0.44 (0.35-0.55) Baxter, 2012 SEER-Medicare 0.40 (0.37-0.43) 0.24 (0.21-0.27) 0.58 (0.53-0.64) Baxter et al. Ann Inter Med 2009; 150: 1-8 Singh et al. Gastroenterology 2010;139:1128–37 Brenner et al. Ann Inter Med 2011;154: 22–30 Baxter et al. J Clin Oncol 2012; 30:2664-9.

Right/Left in the VHA Case-control study, VA-Medicare, patients aged ≥ 75 - 623 cases with CRC, 1869 controls without CRC - Exposure to lower GI endoscopy associated with 42% CRC reduction (aOR 0.58, 95% CI 0.48-0.69) - Colonoscopy associated with significant reductions in: Distal CRC (aOR 0.45, 0.32-0.62) Proximal CRC (aOR 0.65, 0.46- 0.92) Kahi et al. Gastroenterology 2014; 146(3): 718-25.

Interval CRC - Interval CRC (postcolonoscopy CRC): Diagnosed after colonoscopy, within interval until next colonoscopy - Account for 3.4% to 9% of all CRC cases - Diagnosed primarily in the right colon - Endoscopist-related variables are the most important risk factor for interval CRC - 71% to 86% of interval CRC attributable to missed or incompletely resected polyps Bressler et al. Gastroenterology 2007; 132:96-102 Singh et al. Am J Gastroenterol 2010; 105: 2588-96 Farrar et al. CGH 2006: 4:1259-64 Cooper et al. Cancer 2012; 118: 3044-52 Robertson et al. Gut 2014; 63: 949-56 Pohl et al. CGH 2010; 8: 858-64.

Incomplete Resection CARE study 346 polyps 5-20 mm, margins biopsied IRR for neoplastic polyps: 10.1% Incomplete resection more common for: - Large vs. small neoplastic polyps (17.3% vs 6.8%; P=0.003) - SSA/P vs other neoplastic polyps (31.0% vs 7.2%; P<0.001) Nearly half (47.6%) of all large (10–20 mm) SSA/P incompletely removed. Pohl et al. Gastroenterology 2013;144:74–80

Factors affecting right-sided protection REVERSIBLE: Bowel prep (split is now standard of care) Operator Dependent - Cecal Intubation - Withdrawal time and technique - Adenoma detection - Detection of flat and depressed (non-polypoid) neoplasms - Detection of serrated lesions - Complete polypectomy - Operator specialty IRREVERSIBLE: Tumor Biology Rex.Gastroenterology 2011; 140: 19-21 Rex et al. Am J Gastro 2015; 110: 72-90

Performance target (%) Quality indicator Performance target (%) Preprocedure  1. Frequency with which colonoscopy is performed for an indication that is included in a published standard list of appropriate indications, and the indication is documented Process >80  2. Frequency with which informed consent is obtained, including specific discussions of risks associated with colonoscopy, and fully documented >98  3. Frequency with which colonoscopies follow recommended post-polypectomy and post-cancer resection surveillance intervals and 10-year intervals between screening colonoscopies in average-risk patients who have negative examination results and adequate bowel cleansing (priority indicator) ≥90  4. Frequency with which ulcerative colitis and Crohn's colitis surveillance is recommended within proper intervals Intraprocedure  5. Frequency with which the procedure note documents the quality of preparation  6. Frequency with which bowel preparation is adequate to allow the use of recommended surveillance or screening intervals ≥85 of outpatient examinations  7. Frequency with which visualization of the cecum by notation of landmarks and photodocumentation of landmarks is documented in every procedure (priority indicator)     Cecal intubation rate with photography (all examinations)   Cecal intubation rate with photography (screening) ≥95  8. Frequency with which adenomas are detected in asymptomatic average-risk individuals (screening) (priority indicator) Outcome   Adenoma detection rate for male/female population ≥25   Adenoma detection rate for male patients ≥30   Adenoma detection rate for female patients ≥20  9a. Frequency with which withdrawal time is measured  9b. Average withdrawal time in negative-result screening colonoscopies ≥6 min  10. Frequency with which biopsy specimens are obtained when colonoscopy is performed for an indication of chronic diarrhea  11. Frequency of recommended tissue sampling when colonoscopy is performed for surveillance in ulcerative colitis and Crohn's colitis  12. Frequency with which endoscopic removal of pedunculated polyps and sessile polyps <2 cm is attempted before surgical referral Postprocedure  13. Incidence of perforation by procedure type (all indications vs colorectal cancer screening/polyp surveillance) and post-polypectomy bleeding   Incidence of perforation—all examinations <1:500   Incidence of perforation—screening <1:1000   Incidence of post-polypectomy bleeding <1%  14. Frequency with which post-polypectomy bleeding is managed without surgery  15. Frequency with which appropriate recommendation for timing of repeat colonoscopy is documented and provided to the patient after histologic findings are reviewed Rex et al. Am J Gastro 2015; 110: 72-90

Preprocedure  1. Frequency with which colonoscopy is performed for an indication that is included in a published standard list of appropriate indications, and the indication is documented Process >80%  2. Frequency with which informed consent is obtained, including specific discussions of risks associated with colonoscopy, and fully documented >98%  3. Frequency with which colonoscopies follow recommended post-polypectomy and post-cancer resection surveillance intervals and 10-year intervals between screening colonoscopies in average-risk patients who have negative examination results and adequate bowel cleansing (priority indicator) ≥90%  4. Frequency with which ulcerative colitis and Crohn's colitis surveillance is recommended within proper intervals

Intraprocedure  5. Frequency with which the procedure note documents the quality of preparation Process >98%  6. Frequency with which bowel preparation is adequate to allow the use of recommended surveillance or screening intervals ≥85% of outpatient exams  7. Frequency with which visualization of the cecum by notation of landmarks and photodocumentation of landmarks is documented in every procedure (priority indicator)   Cecal intubation rate with photography (all examinations)   ≥90%   Cecal intubation rate with photography (screening) ≥95%  8. Frequency with which adenomas are detected in asymptomatic average-risk individuals (screening) (priority indicator) Outcome   Adenoma detection rate for male/female population ≥25%   Adenoma detection rate for male patients ≥30%   Adenoma detection rate for female patients ≥20%  9a. Frequency with which withdrawal time is measured  9b. Average withdrawal time in negative-result screening colonoscopies ≥6 min  10. Frequency with which biopsy specimens are obtained when colonoscopy is performed for an indication of chronic diarrhea  11. Frequency of recommended tissue sampling when colonoscopy is performed for surveillance in ulcerative colitis and Crohn's colitis  12. Frequency with which endoscopic removal of pedunculated polyps and sessile polyps <2 cm is attempted before surgical referral

Postprocedure  13. Incidence of perforation by procedure type (all indications vs colorectal cancer screening/polyp surveillance) and post-polypectomy bleeding Outcome     Incidence of perforation—all examinations <1:500   Incidence of perforation—screening <1:1000   Incidence of post-polypectomy bleeding <1%  14. Frequency with which post-polypectomy bleeding is managed without surgery ≥90  15. Frequency with which appropriate recommendation for timing of repeat colonoscopy is documented and provided to the patient after histologic findings are reviewed. Process

REVIEW OF SELECTED COLONOSCOPY QUALITY MEASURES Cecal Intubation Rate Withdrawal Time Adenoma Detection Rate - Polyp Detection Rate - Adenoma per Colonoscopy Rate.

Cecal Intubation Rate Cecal intubation: Passage of scope tip proximal to IC valve, allowing visualization of entire cecal caput including medial wall Fundamental step to assess colonoscopy completeness and quality Effective endoscopists should be able to achieve rates of ≥ 90% in all cases, and ≥ 95% in screening colonoscopies Current data suggest adequate CIR in the US (97% or higher) Risk of interval CRC decreased if CIR ≥ 95% compared to < 80% Distal OR: 0.73 (0.54-0.97) Proximal OR: 0.72 (0.53-0.97) Baxter et al. Gastroenterology 2011; 140: 65-72.

Withdrawal Time Detection of lesions is increased when average withdrawal time is ≥ 6 minutes Metric applies for screening examinations in intact colons, with no biopsy/polypectomy performed UK study with > 31,000 colonoscopies: - Colonoscopists with WT < 7 min had ADR 42.5%, versus WT > 11 min had ADR 47.1% (p< 0.001) - No incremental yield beyond WT of 10 min Lee et al. Endoscopy 2013; 45: 20-6 Study from Minnesota, about 77,000 screening colonoscopies by 51 MDs - Longer mean WT associated with higher ADR (3.6% per minute) - Interval CRC: Compared with WT ≥6 min, the adjusted incidence rate ratio for WT <6 minutes was 2.3 (95% CI: 1.5−3.4; P < .0001). Shaukat et al. Gastroenterology 2015 (In press).

Withdrawal Time Longer withdrawal time implies careful, more thorough colon mucosa inspection Better technique almost invariably requires more time: Cleansing, distention, examination of proximal side of folds Despite increased detection of polyps with longer WT, WT still secondary to ADR, especially for high-level detectors WT may be most relevant to correct the performance of physicians with low ADR. Rex et al. Am J Gastro 2015; 110: 72-90.

Adenoma Detection Rate ADR = Surrogate measure for CRC incidence and interval CRC incidence, which are not practical to measure for quality interventions Rationale for measuring ADR originally based on large variability in adenoma detection between endoscopists Benchmarks first proposed in 2002 Proportion of screening colonoscopies where at least one adenoma is detected Targets: Men: ≥ 30% Women: ≥ 20% Mixed male/female population: ≥ 25% Rex et al. Am J Gastro 2015; 110: 72-90.

ADR: Validation (and vindication) Polish screening colonoscopy study - 45,000 subjects, 186 endoscopists - Patients whose endoscopists’ ADR was < 20% had at least 10-fold higher risk to be diagnosed with interval CRC, compared to those whose endoscopists had ADR ≥ 20% - Interval CRC risk increased as ADR decreased Kaminski et al. NEJM 2010; 362: 1795-1803.

ADR: Validation (and vindication) Kaiser Permanente screening colonoscopy study - 315,000 subjects, 136 endoscopists - ADR ranges 7.4% to 52.5% - ADR independent predictor of interval CRC:  HR 0.52 (0.35-0.69) for patients scoped by endoscopists with ADR > 33.5% versus those with ADR < 19% - Interval CRC risk decreased with increasing ADR, proximal and distal colon - No “ceiling” effect for ADR - Risk of interval CRC decreased by 3% for each 1% ADR increase - Risk of fatal CRC decreased by 62% for patients scoped by endoscopists with highest ADR Corley et al. NEJM 2014; 370: 1298-1306.

Corley et al. NEJM 2014; 370: 1298-1306

Corley et al. NEJM 2014; 370: 1298-1306.

ADR Measurement Best overall measure of quality Indirectly reflects other factors such as prep, WT, technique Relatively straightforward to measure, but requires process for periodic review of pathology data Requires a large number of screening colonoscopies per provider (500 provides narrow 95% confidence intervals) Colonoscopies for other indications not part of standard ADR Serrated lesions not included Limitations: Process required to measure (may include manual chart review) “One and done” risk.

Polyp Detection Rate PDR = Surrogate measure for ADR Proportion of screening colonoscopies where at least one polyp is detected Advantage: No need for manual pathology entry, collected automatically with procedure reports/billing Correlates well with ADR William et al. Gastrointest Endosc 2012; 75: 576-82 No prospective data regarding its validity as quality measure independent of ADR Limitations: Surrogate of a surrogate Even more corruptible than ADR Fayad and Kahi CGH 2014; 12: 1973-80.

Adenoma Per Colonoscopy (APC) Rate Total number of adenomas divided by total number of screening colonoscopies Better “global” measure of adenoma detection - 42,000 colonoscopies, 316 French endoscopists - For MDs with ADR around 35%, APC varied from 0.36 to 0.98 Denis et al. Dig Liv Dis 2014; 46:176-81 Overcomes “one and done” issue with standard ADR Limitations: Could increase costs if providers have to submit adenomas in separate bottles Additional validation studies needed.

Kahi et al. Gastrointest Endosc 2014;79:448-54.

Not just adenomas…

A Changing Paradigm 1990: Almost all colorectal cancers (CRC) develop along the Vogelstein model (adenoma-carcinoma sequence) Normal epithelium Dysplastic ACF Early adenoma Late adenoma Cancer Metastatic cancer APC K-Ras P53

Basic Molecular Pathways in CRC Chromosomal Instability (CIN) Pathway---60%-70% - Adenoma-carcinoma sequence Mutator Pathway---5% Defective DNA mismatch repair (hMLH1, hMSH2, hMSH6, hPMS2) Microsatellite instability (MSI) Example: Lynch syndrome Serrated pathway---25%-35% - BRAF oncogene mutations - Epigenetic DNA promoter hypermethylation leading to the CpG island methylator phenotype (CIMP) - MSI +/-

WHO Classification of Serrated Colonic Lesions Hyperplastic Polyp - Microvesicular HP (MVHP) - Goblet-cell rich HP (GCHP) - Mucin-poor HP (MPHP) Sessile Serrated Adenoma/Polyp (SSA/P) - SSA/P without cytological dysplasia - SSA/P with cytological dysplasia Traditional Serrated Adenoma (TSA) Snover D, et al. WHO classification of tumours. Pathology and genetics. Tumours of the digestive system. 4th edition. Berlin: Springer-Verlag. 2010.

“Main” Serrated Pathway BRAF mutation Normal mucosa Promoter hypermethylation MVHP hMLH1 hypermethylation Epigenetic silencing SSA/P Accelerated progression SSA/P-CD CANCER CIMP-high MSI Variable Progression Rapid Progression (Lynch-like) Snover D, et al. WHO classification of tumours. Pathology and genetics. Tumours of the digestive system. 4th edition. Berlin: Springer-Verlag. 2010. Kahi C. Dig Dis Sci 2015; 60: 773-80.

Endoscopic Features-SSA/P Flat, subtle appearance Larger than hyperplastic polyps Typically proximal colon Mucus cap Similar in color to surrounding mucosa Can be reliably distinguished from adenomas, but differentiation from HP is more challenging. Vu et al. Dis Colon Rectum 2011; 54:1216-23 Jaramillo et al. Endoscopy 2005; 37: 254-60

SSA/P: Most prevalent visual descriptors - Mucus cap (64%) - Rim of debris or bubbles (52%) - Alteration of the contour of a fold (37%) - Interruption of underlying mucosal vascular pattern (32%) Tadepalli et al. Gastrointest Endosc 2011; 74: 1360-8

What is True Prevalence of SSA/P? Studies reporting SSA/P prevalence rates generally reported aggregate data for groups of endoscopists with significant variability in individual detection rates Recent study attempted to overcome these limitations: - Colonoscopy database of an endoscopist with high polyp detection rate, combined with histological review by an expert in serrated lesion pathology - 1910 average-risk patients - Prevalence of SSA/P was 8.1 % (0.6 % for SSA/P-CD) Abdeljawad et al. Gastrointest Endosc. 2015 Mar;81(3):517-24.

Serrated Pathway and Interval CRC: Overlap of Molecular Signatures Compared to non-interval CRC, interval CRC more likely to: - Be located in the proximal colon - Demonstrate MSI - Be associated with CIMP Sawhney et al. Gastroenterology 2006; 131: 1700-5 Arain et al. Am J Gastroenterol 2010; 105: 1189-95 Nishihara et al. NEJM 2013; 369: 1095-1105. Nurses’ Health Study and the Health Professionals Follow-up Study - 88,902 subjects, 22-year follow-up - Cancers diagnosed within 5 years of colonoscopy twice more likely to have CIMP and microsatellite instability

Variable detection of proximal serrated lesions Author (year) N screening colons N endoscopists polyps ADR PSP-DR Hetzel (2010) 7192 13 4535 13.5%-36.4% 1.4%-7.6% Kahi (2011) 6681 15 11,049 17%-47% 1%-18% De Wijker-slooth (2013) 1354 5 1635 24%-40% 6%-22% Payne (2014) 7215 32 sites 5548 17.4%-43.5% 0%-9.8% Hetzel et al. Am J Gastroenterol. 2010; 105: 2656-64 Kahi et al. Clin Gastroenterol Hepatol. 2011; 42-6 De Wijkerslooth et al. Gastrointest Endosc 2013; 77: 617-23 Payne et al. Clin Gastroenterol Hepatol 2014;12:1119–26.

Incomplete Resection: CARE study 346 polyps 5-20 mm, margins biopsied About 10% of polyps were incompletely resected Incomplete resection more common for: - Large vs. small neoplastic polyps (17.3% vs 6.8%; P=0.003) - SSA/P vs other neoplastic polyps (31.0% vs 7.2%; P<0.001) Nearly half (47.6%) of all large (10–20 mm) SSA/P incompletely removed. Pohl et al. Gastroenterology 2013;144:74–80

Optimizing Detection of Serrated Polyps: Take your time and look again! Longer WT associated with better proximal SP detection, but not patient age, sex, or prep quality De Wijkerslooth et al. Gastrointest Endosc 2013; 77: 617-23 Incident rate ratio for SP detection increases with each minute of WT above 6 minutes, with maximum benefit at 9 minutes If minimum WT set at 9 minutes, modeling predicts a 30% relative increase in SP detection (2.4% more patients) Butterly et al. Am J Gastroenterol 2014;109:417–26.

“ I don’t measure colonoscopy quality”

Implementation Select the metric to be measured (at least ADR) - Determine how to define ADR, e.g. first time screening colonoscopies only, include patients with family history? Collect measurements for baseline - Look for patterns - Metric already high enough (CIR 100%)? - How cumbersome, can process be automated? Study and Intervention phase PDSA cycle (Plan-Do-Study-Act) Calderwood and Jacobson. Gastroenterology Clinics of North America, 2013 Volume 42, Issue 3, Pages 599-618.

Gastroenterology Clinics of North America. Calderwood, Audrey H., MD; Jacobson, Brian C., MD, MPH. Published September 1, 2013. Volume 42, Issue 3. Pages 599-618.

Documentation is Key to Implementation Key subject areas for colonoscopy report Patient demographics and history Assessment of patient risk and comorbidity Procedure indication(s) Procedure: technical description Colonoscopic findings Assessment Interventions/unplanned events Follow-up plan Pathology CO-RADS to improve the quality of colonoscopy From Lieberman D, Nadel M, Smith RA, et al. Standardized colonoscopy reporting and data system: report of the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. Gastrointest Endosc 2007;65:75.

Interventions to Improve Quality Interventions focused on lengthening withdrawal time and/or providing feedback to endoscopists: Inconsistent effect on ADR. Corley et al. Gastrointest Endosc 2011;74:656-65. Educational interventions are most promising: EQUIP (training module to improve neoplasia recognition and teach techniques to improve ADR) Endoscopists randomized to EQUIP had significantly improved ADR (36% to 47%). Coe et al. Am J Gastroenterology 2013; 108: 219-26.

Interventions to Improve Quality: Hawthorne Effect Hawthorne effect: the alteration of behavior by the subjects of a study due to their awareness of being observed. A quarterly “report card” results in significantly higher ADR/CIR: ADR: 53.9% vs 44.7% P = .013 CIR: 98.1% vs 95.6% P = .027 Kahi et al. Gastrointest Endosc 2013; 77: 925-31 Awareness of being videorecorded results in longer inspection time and improved technique Rex et al. Am J Gastro 2010; 105: 2312-7.

QUALITY IS A TEAM RESPONSIBILITY Nurse observation during colonoscopy significantly increases polyp detection, including flat polyps Aslanian et al. Am J Gastroenterology 2013; 108: 166-72 Lee et al. Gastrointestinal Endoscopy 2011; 74: 1094-1102 Cardinal rules for GI nurses and techs: - Observe, look at monitor - Be active participants in the procedure - Speak up! Champion quality monitoring and improvement programs.