Colorectal Cancer Screening Guideline

Colorectal Cancer Screening Guideline Major Changes as of May 2014 2 Background 2 Definitions 3 Prevention 3 Screening Definitions: average and increased risk 4 Recommendations by age group 4 Recommended screening tests 4 Other screening tests 5 Screening tests that are not recommended 5 Recommendations for patients at average risk 6 Shared decision-making 6 Recommendations for patients at increased risk 7 Referral to Genetics 8 Follow-up 8 Evidence Summary 9 References 14 Guideline Development Process and Team 16 Last guideline approval: May 2014 Guidelines are systematically developed statements to assist patients and providers in choosing appropriate health care for specific clinical conditions. While guidelines are useful aids to assist providers in determining appropriate practices for many patients with specific clinical problems or prevention issues, guidelines are not meant to replace the clinical judgment of the individual provider or establish a standard of care. The recommendations contained in the guidelines may not be appropriate for use in all circumstances. The inclusion of a recommendation in a guideline does not imply coverage. A decision to adopt any particular recommendation must be made by the provider in light of the circumstances presented by the individual patient. Colorectal Cancer Screening Guideline 1 Copyright 1996 2014 Group Health Cooperative. All rights reserved.

Major Changes as of May 2014 New Screening Tests Flexible sigmoidoscopy Flexible sigmoidoscopy is no longer performed in Group Health primary care settings. It remains available in Gastroenterology. If selected, flexible sigmoidoscopy every 5 years must be combined with an annual fecal immunochemical test (FIT). Populations If family history is not known, consider beginning screening African-Americans at age 45. For all other average-risk individuals, we continue to recommend starting screening at age 50. Previous Screening for patients at increased risk This entire section has been updated. See Table 4 on page 7. Flexible sigmoidoscopy was performed in four Group Health primary care settings (Everett, Federal Way, and Olympia medical centers and the Family Health Center in Seattle), in addition to Gastroenterology. If selected, flexible sigmoidoscopy every 5 years must be combined with a FIT every 3 years. Group Health recommends starting screening at age 50 for all average-risk individuals. Background Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of cancer deaths in the United States. There is good evidence that CRC-related morbidity and mortality can be reduced through early detection and treatment of early-stage disease and through the identification and removal of adenomas, the precursor of colorectal cancers. Colorectal Cancer Screening Guideline 2

Definitions Adenomatous polyps (also called adenomas) are dysplastic polyps with malignant potential, and are the most common type of colon polyp. Nearly all colorectal cancers arise from adenomas, but only a small minority of adenomas progress to cancer (5% or less). Adenomatous polyps may be classified as: Tubular adenoma adenoma with villous component of 25% or lower. Most common type of adenoma. Tubulovillous adenoma (TVA) adenoma with 26 74% villous component. Villous adenoma adenoma with at least 75% villous component. Serrated polyps (or serrated adenomas) have variable malignant potential, and may be classified as: Sessile serrated adenoma pre-malignant flat (or sessile) lesion. Typically seen in the proximal colon and often lacking classic cytological dysplasia. Serrated adenoma pre-malignant polyp. More prevalent in rectosigmoid and often with mild cytologic dysplasia. Hyperplastic polyp polyp with low potential to become malignant. Small in size, most prevalent in the distal colon. Advanced adenoma high-risk adenoma characterized by high-grade dysplasia, size 10 mm, or any villous component. Prevention Diet and calcium supplements There is insufficient evidence to determine if the following approaches to preventing colorectal cancer have benefit: Avoiding red meat and alcohol. Consuming foods very high in fiber. Taking calcium supplements greater than 1,200 mg. Aspirin and NSAIDs Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for patients at average risk. Although certain NSAIDs are associated with regression and decreased incidence of colonic adenomas, the harms of daily NSAID use in asymptomatic people led the U.S. Preventive Services Task Force to recommend against the routine use of aspirin and NSAIDs to prevent colorectal cancer in individuals at average risk (USPSTF 2008). This recommendation does not apply to individuals with familial adenomatous polyposis, hereditary nonpolyposis colon cancer syndromes (Lynch I or II), or a history of colorectal cancer or adenomas. Colorectal Cancer Screening Guideline 3

Screening Colorectal cancer risk groups Average risk: Patients aged 50 years or older with no personal history of CRC or adenomas, no inflammatory bowel disease, and with a negative family history. Increased risk: Patients with a personal or family history of CRC or related conditions. (See Table 4 for more detail.) CRC screening recommendations by age group Table 1. Colorectal cancer screening recommendations by age group Age Recommendation 30 through 49 years Review family history to identify patients at increased risk for CRC (see Table 4) or at high risk for inherited cancer syndromes (see Referral to Genetics section). For African-American patients whose family history is not known, consider beginning routine screening at age 45. 1 50 through 75 years Routine screening for patients at average risk (Table 2) and at increased risk (Table 4). 76 through 84 years Due to lack of evidence of benefit versus harm, consider routine screening only for patients who have not been up to date with screening prior to age 75 years and/or who are healthy and have a life expectancy of 10 years or more. 85 years and older Screening is not recommended. 1 There is evidence of a higher incidence of colorectal cancer in African-Americans, and a higher agespecific incidence rate for those under age 50, compared to other races. However, personal and family histories are the most important independent factors in determining age at initial screening and screening frequency. Recommended screening tests at Group Health medical facilities The fecal immunochemical test (FIT) Average-risk patients: Annual FIT is the preferred method for screening because the net benefit is similar to more invasive techniques; it is rapidly accessible, lower cost, and low risk; and it conserves colonoscopy resources for patients who are at higher risk or those who test positive on stool-screening tests. Colonoscopy Average-risk patients: Colonoscopy at 10-year intervals is an alternative screening method for patients or providers who prefer this approach and for patients who may have difficulty with an annual FIT testing regimen. Patients should be informed of the differences in potential risks and costs associated with colonoscopy compared with annual stool testing. Increased-risk patients: Colonoscopy is the only screening method recommended for patients with a personal or family history of CRC or related conditions. See Table 4 for recommended screening frequency and age at initial screening. Note: If there are contraindications to colonoscopy, virtual colonoscopy may be considered. See Clinical Review Criteria for Virtual Colonoscopy or CT Colonography. Colorectal Cancer Screening Guideline 4

Other screening tests Flexible sigmoidoscopy Average-risk patients: If a patient requests it, flexible sigmoidoscopy at 5-year intervals should only be done in addition to annual FIT screening. Flexible sigmoidoscopy is no longer performed in Group Health primary care settings. Patients who request flexible sigmoidoscopy should be referred to Gastroenterology. Screening tests that are not recommended The following tests are not currently recommended as a primary screening tool for colorectal cancer: Guaiac-based stool test Double contrast barium enema Stool DNA Virtual colonoscopy may be considered if there are contraindications to colonoscopy. See Clinical Review Criteria for Virtual Colonoscopy or CT Colonography.. Colorectal Cancer Screening Guideline 5

Screening recommendations for patients at AVERAGE risk Table 2. Colorectal cancer screening for patients at AVERAGE risk Average risk is defined as aged 50 years or older with no personal history of CRC or adenomas, no inflammatory bowel disease, and with a negative family history. Test Age at initial screening Frequency Fecal immunochemical test (FIT) (preferred) 50 years Annually through age 75 Colonoscopy 50 years Every 10 years through age 75 Shared decision making Because several screening strategies have similar efficacy, efforts to reduce colorectal cancer deaths should focus on implementing strategies that maximize the number of patients who get screening of some type. The different CRC screening options are variably acceptable to patients; eliciting patient preferences is one step in improving adherence. Ideally, shared decision making between clinicians and patients would incorporate information on local test availability and quality, as well as patient preference (USPSTF 2008). Table 3. Shared decision making regarding colorectal cancer screening options (patients at AVERAGE risk) Advantages/benefits FIT (fecal immunochemical test ) Can be done at home. Requires no advance preparation, dietary modification, or loss of time from work. Noninvasive. No risk of bowel tears or infections. Minimal handling of stool. There is strong evidence that stool screening with FIT (followed by colonoscopy when positive) decreases CRC mortality. Disadvantages/risks Colonoscopy is required if FIT is positive. May fail to detect cancer; high rate of false negatives. Must be done annually to be an effective screening method adherence is important to the effectiveness of program. Focused on early detection rather than prevention of colon cancer. Colonoscopy Views entire colon. Direct visualization techniques offer greater sensitivity for adenomas. Has potential to prevent colon cancer by detecting and removing adenomatous polyps. Requires testing only every 10 years. Flexible sigmoidoscopy Allows for biopsy and removal of adenomatous polyps. Office procedure. Does not require sedation. Has potential to prevent colon cancer by detecting and removing adenomatous polyps. Requires full bowel prep. Effectiveness of colonoscopy diminished if bowel prep is incomplete. Sedation usually needed. Requires loss of time from work. Risk of bowel tears is higher than other options. Can only detect lesions to level of insertion of the scope. No visualization of the proximal colon. Colonoscopy necessary if abnormalities detected. Should only be done in combination with annual FIT. Colorectal Cancer Screening Guideline 6

Screening recommendations for patients at INCREASED risk Table 4. CRC screening for patients at INCREASED risk Increased risk is defined as a personal or family history of CRC or related conditions. Eligible population Test Age at initial screening Personal history CRC or adenomatous polyps Colonoscopy Consult with Gastroenterology. Inflammatory bowel disease (Crohn s disease, ulcerative colitis) Family history 1 first-degree relative 1 with CRC diagnosed at age < 60 years or 2 first-degree relatives 1 with CRC diagnosed at any age 1 first-degree relative 1 with CRC diagnosed at age 60 years 1 first-degree relative 1 with advanced adenoma 2 diagnosed at any age 1 second-degree relative 3 with CRC diagnosed at age < 50 years 1 2 3 Colonoscopy Colonoscopy Consult with Gastroenterology. Whichever comes first: Age 40 or 10 years prior to earliest age of diagnosis Frequency Consult with Gastroenterology. Every 1 2 years Every 3 5 years Colonoscopy Age 50 Every 5 years Colonoscopy Whichever comes first: Age 50 or Age of diagnosis May lengthen interval after 2 negative colonoscopies. Repeat per colonoscopy findings. Colonoscopy Age 50 Repeat per colonoscopy findings. First-degree relative = parent, sibling, or child. Advanced adenomas meet any of these criteria: high-grade dysplasia, 10 mm, any villous component. Second-degree relative = grandparent, aunt, uncle, niece, nephew. Colorectal Cancer Screening Guideline 7

Referral to Genetics Refer patients with any of the following to Genetics for further risk evaluation/assessment for high-risk cancer syndromes: Personal history of colorectal cancer (CRC) before age 50 Personal history of CRC and endometrial cancer at any age Personal history of CRC and ovarian cancer at any age Personal history of CRC and two first-degree relatives with history of colorectal, endometrial, or ovarian cancer at any age Family history of inherited syndromes such as Lynch, FAP, or familial diffuse gastric cancer Personal history of 10 or more adenomatous polyps (> 20 for Medicare to cover testing) Personal history of multiple primary colon cancers at any age Follow-up Table 5. Follow-up of screening test results Test Result Follow-up testing FIT Negative Repeat screening in 1 year with one of the options for average-risk patients (Table 2). Colonoscopy Positive Normal or Hyperplastic polyp(s) Low-risk adenoma(s) 1 Refer for colonoscopy. Screen again in 10 years with one of the options for average-risk patients (Table 2). Repeat colonoscopy in 5 years. Flexible sigmoidoscopy 1 2 Advanced or multiple adenoma(s) 2 Normal or Hyperplastic polyps(s) Adenoma(s) Generally, if no lesions are found on the second colonoscopy, screen again in 10 years with one of the options for average-risk patients (Table 2). Consult with Gastroenterology to determine followup testing recommendations. Continue annual screening with FIT, and Repeat flexible sigmoidoscopy at 5 years, or Do colonoscopy at 10 years. OR Continue annual screening with FIT alone. Refer for colonoscopy. Low-risk adenomas = 1 or 2, < 10 mm, tubular. Advanced or multiple adenomas meet any of these criteria: 3 10, high-grade dysplasia, 10 mm, any villous component. Colorectal Cancer Screening Guideline 8

Evidence Summary To develop the Colorectal Cancer Screening Guideline, Group Health has adapted the following externally developed evidence-based guidelines: National Comprehensive Cancer Network Guidelines: Genetic/Familial High-Risk Assessment: Colorectal (NCCN 2014) National Comprehensive Cancer Network Guidelines: Colorectal Cancer Screening (NCCN 2014) Kaiser Permanente Colorectal Cancer Screening Clinical Practice Guideline (Kaiser Permanente 2012) Kaiser Permanente Northern California Clinical Practice Guidelines: Colorectal Cancer Screening (Kaiser Permanente 2013) Institute for Clinical Systems Improvement (ICSI) Colorectal Cancer Screening Health Care Guideline (Brink 2012) Screening for Colorectal Cancer: A guidance statement from the American College of Physicians (Qaseem 2012) Screening for Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement (USPSTF 2008) Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology (Levin 2008) The Group Health guideline team reviewed additional evidence in the following areas: Fecal immunochemical test (FIT) versus fecal occult blood test (FOBT) FIT versus optical colonoscopy Flexible sigmoidoscopy Virtual colonography Complications of colonoscopy Prevention There is good evidence from a meta-analysis of 2 randomized controlled trials (RCTs) that calcium supplementation greater than 1,200 mg per day significantly reduces the risk of adenomas (Carroll 2010). A recent meta-analysis of prospective cohort studies (Keum 2014) showed a linear dose response association between calcium intake (250 1900 mg/day) and decreased risk of CRC (8% decrease in risk for every 300 mg/day increase in calcium intake). The relationship was observed for dietary and supplementary calcium, for both men and women, and was more consistent with colon cancer than rectal cancer. This relationship was not confirmed in long-term RCTs to date. There is good evidence from a meta-analysis of RCTs that aspirin is effective for the prevention of colorectal adenomas (Cole 2009). There is evidence from a meta-analysis of cohort studies that regular long-term (> 5 years) use of low-dose aspirin can effectively reduce the risk of colorectal cancer (Ye 2013). A meta-analysis of 25 prospective studies indicates that high intake of dietary fiber, in particular cereal fiber and whole grains, is associated with a reduced risk of colorectal cancer (Aune 2011). An earlier meta-analysis of 5 RCTs did not find a significant reduction in the incidence of recurrent adenomas or colorectal cancer among individuals with a history of adenomatous polyps assigned to dietary fiber versus control (Asano 2002). It is difficult to know from this negative finding whether dietary fiber is ineffective or whether the analysis was underpowered or otherwise flawed. Colorectal Cancer Screening Guideline 9

Screening average-risk individuals Stool-based testing (fecal tests) Evidence of benefit A Cochrane review pooled the findings of 4 major RCTs and found a statistically significant reduction in colorectal cancer mortality with FOBT screening (followed by endoscopy when positive). The pooled RR = 0.84 (95% CI, 0.78 0.90). The number needed to screen (NNS) with guaiac-based FOBT screening to prevent 1 death from colorectal cancer over 10 years was 1,173 (Hewitson 2007, updated 2011). FIT vs. FOBT: A meta-analysis of 5 studies that compared adherence and detection rates of CRC screening by type of screening test (Hassan 2012) showed that FIT was superior to gfobt for the adherence rate (51.66% and 40.91%, respectively) and detection rate for advanced neoplasia and cancer (1.14% with FIT and 0.46% with gfobt, with an NNS=145). Another meta-analysis (Vart 2012) of 7 trials also showed that the participation rates for FIT were significantly higher than those for gfobt. However, the reasons for the difference were inconclusive. Evidence of harm While evidence is lacking, harms from FOBT are estimated by the USPSTF systematic review to be no greater than small (USPSTF 2008). Flexible sigmoidoscopy Evidence of benefit There is strong evidence that colorectal cancer (CRC) screening with flexible sigmoidoscopy (FSG) prevents CRC and reduces related deaths. The Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial (Schoen 2012), sponsored by the National Cancer Institute, randomized 154,900 men and women 55 74 years of age to screening with FSG with a repeat exam at 3 5 years or to usual care. The primary endpoint of the trial was death from colorectal cancer; secondary endpoints included incidence of CRC, stage of the disease, survival, allcause mortality, and harms of screening. Most patients with abnormal FSG results underwent colonoscopy for diagnostic follow-up. The results of the trial showed that after a median follow-up of 11.9 years, the incidence of CRC was significantly lower in the screened group than in the usual-care group (RR = 0.75; 95% CI, 0.72 0.85), with a number needed to invite for screening to prevent 1 case of CRC of 282 (95% CI, 210 427). The significant reduction in cancer incidence was observed for both distal and proximal colorectal cancers. CRC-related mortality was also significantly reduced in the screening versus standard care groups, with an RR of 0.74 (95% CI, 0.63 0.87) and a number needed to invite for screening to prevent 1 CRC-related death of 871 (95% CI, 567 1874). The benefit on CRC-related mortality was, however, site-specific; mortality was significantly reduced in individuals with distal CRC (RR = 0.50; 95% CI, 0.38 0.64) but was unaffected in those with proximal CRC (RR = 0.97; 95% CI, 0.77 1.22). The trial had valid methodology; however, there was a high degree of contamination, as 47% of the participants in the usual-care group underwent flexible sigmoidoscopy or colonoscopy. This would mask the actual benefit of FSG screening. Similar results were observed in two other European trials. The UK trial (Atkin 2010) showed that onetime FSG performed on patients between the ages of 55 and 64 significantly reduced the incidence of colorectal cancer and its associated mortality. The number needed to screen to prevent 1 CRC diagnosis was 191 and the number needed to screen to prevent 1 CRC death was 489. The SCORE trial, a large RCT conducted in Italy (Segnan 2011), evaluated the effect of flexible sigmoidoscopy screening on CRC incidence and mortality in 34,272 individuals followed up for a median duration of 10.5 years. The results showed that a single FSG screening between the ages of 55 and 64 years was associated with a significant reduction in CRC incidence, but with a statistically insignificant reduction in mortality according to the intention-to-treat (ITT) analysis. (The per-protocol analysis showed a significant reduction in both CRC incidence and mortality). Colorectal Cancer Screening Guideline 10

A Norwegian trial on the other hand, showed no benefit of sigmoidoscopy screening after 7 years of follow-up (Hoff 2009). Littlejohn and colleagues meta-analysis (2012) of 14 RCTs, which compared FSG screening versus screening with fecal tests or no screening, indicates that FSG may be more effective than stool-based tests in detecting advanced adenomas. FSG was more effective than FOBT but not FIT in detecting CRC. One meta-analysis of RCTs that included the long-term results of the PLCO trial showed that FSG-based screening for colorectal cancer significantly reduced CRC incidence and CRC-related mortality in average-risk individuals (Elmunzer 2012). The results of these last two meta-analyses should be interpreted with caution due to several limitations: 1) The studies had valid methodology, but differed in the population enrolled, screening strategy, definition of polyps, and duration of follow-up, 2) there was a significant heterogeneity for the outcome of CRC incidence, mainly due to the short follow-duration of the Norwegian trial, 3) the studies were conducted mainly in North America and Europe, which limits the generalization of their results, and 4) flexible sigmoidoscopy was compared to no screening, and not to the stool-based testing or colonoscopy. Evidence of harm The USPSTF evidence review (2008) estimates that the rate of serious complications associated with flexible sigmoidoscopy screening is 3.4 per 10,000 procedures. Serious complications include death and adverse events requiring hospital admission (perforation, major bleeding, diverticulitis, severe abdominal pain, and cardiovascular events). Combined FOBT and flexible sigmoidoscopy Evidence of benefit There is insufficient evidence to determine that screening with both FOBT and flexible sigmoidoscopy reduces the risk of colorectal cancer incidence or CRC-related mortality. Hassan and colleagues metaanalysis (2012) indicates that while the participation rate with the combined testing was significantly lower than with the stool-based tests alone, there were significantly higher detection rates of advanced neoplasia or cancer. Evidence of harm There are no published estimates of harm from combined screening with FOBT and flexible sigmoidoscopy. Colonoscopy Evidence of benefit There is no direct evidence from randomized controlled trials to conclude that screening with colonoscopy reduces the risk of colorectal cancer mortality or colorectal cancer incidence. The evidence of benefit is indirect, derived from case-control and observational studies, and is mostly about detection rate of lesions that may be clinically important. A large case-control study conducted in Canada found a significant association between colonoscopy and a reduced risk of death from left-sided CRC (Baxter 2009). A large prospective closed cohort study in Switzerland that involved 1,912 individuals screened by colonoscopy and 20,774 controls showed significantly lower CRC incidence and cancer-related mortality in the screened cohort (Manser 2012). An ongoing trial, COLONPREV (Quintero 2012), compares one-time colonoscopy versus FIT every 2 years in 53,302 asymptomatic adults 50 69 years of age. The primary outcome of the trial is the rate of death from CRC at 10 years. The study design allowed for crossover between the two study groups. Of those who tested positive with FIT, 86.4% underwent colonoscopy. An interim analysis of the trial showed that subjects in the FIT group were more likely to participate in screening than those in the colonoscopy group. An ITT analysis showed that the detection rate of CRC was 0.1% in each of the two study groups. Advanced adenomas were found in 1.9% in the colonoscopy group and 0.9% in the FIT group (OR = Colorectal Cancer Screening Guideline 11

2.30; 95% CI, 1.97 2.69). Non-advanced adenomas were found in 4.2% and 0.4% in the two groups respectively (OR = 9.80; 95% CI, 8.10 11.85). Detection of adenomas was most evident for lesions in the proximal colon. The detection rate of CRC was statistically insignificant between the two groups (OR = 1.56; 95% CI, 0.93 2.56). The number needed to screen (NNS) to find 1 CRC was 191 in the colonoscopy group and 281 in the FIT group. The NNS to find any advanced neoplasm was 10 and 36, respectively. The number of subjects who needed to undergo a colonoscopy to find 1 CRC was 191 in the colonoscopy group and 18 in the FIT group. The numbers to find any advanced neoplasm were 10 and 2, respectively. Evidence of harm The results of several published studies (Boltière 2013, Denis 2013, Quintero 2012, Ko 2010, and Arora 2009) show the following: Perforation and lower GI bleeding are the most serious complications associated with colonoscopy. The rates of perforation varied between studies from 0.01% to 0.1%. The rates of lower GI bleeding ranged from 0.1% to 0.6%. The risk for serious complications is higher among those who undergo snare polypectomy with cautery. This increases further if more than one polypectomy with cautery is performed. Other risk factors for perforation and bleeding include resection of polyps larger than 1 cm, resection of more than 4 polyps, advanced age, female sex, comorbid conditions, and emergency colonoscopies. The risk of complications may be lower with screening versus diagnostic colonoscopy. In a study of Medicare beneficiaries, Warren and colleagues (2009) reported a risk of 2.4 serious complications per 1,000 screening colonoscopies; 4.2 out of 1,000 diagnostic colonoscopies, and 9.3 out of 1,000 colonoscopies with polypectomy. The USPSTF (2008) reported a rate of 2.8 serious complications per 1,000 screening colonoscopies in predominantly asymptomatic individuals. Colonography (computed tomography colonoscopy, CTC, virtual colonoscopy) In a meta-analysis (de Haan 2011) of 5 heterogeneous studies that was dominated by one large study, the estimated sensitivities of colonography for patients with polyps or adenomas 6 mm were 75.9% and 82.9%, and the corresponding specificities were 94.6% and 91.4%. The pooled results indicate that colonography had an average sensitivity for detecting polyps or adenomas of < 10 mm in diameter, but performed better for polyps or adenomas that were 10 mm in diameter. Colonography did not miss any CRC (100% sensitivity). It had a high specificity for polyps of any size. Colonography was compared to colonoscopy, which is not 100% sensitive, and histologic verification was not performed in all studies. Screening high-risk individuals There is insufficient evidence on how to screen, how often to screen, or when to initiate screening for individuals at high risk of colorectal cancer. Recommendations in this guideline are based on expert opinion. Interventions to improve adherence to colorectal screening The Systems of Support to Increase Colorectal Cancer Screening (SOS) trial (Green 2013), conducted among 4,675 individuals from 21 primary care Group Health clinics, examined the effects of electronic health records (EHRs), automated mailing, and stepped increases in support on improving CRC screening adherence over 2 years among individuals not current in their CRC screening. The results of the study showed that, compared to usual care, all other interventions led to an increase in CRC testing rates, mainly with FOBT. There was an incremental increase in the uptake of CRC testing with the stepped interventions; however, the greatest incremental benefit was observed with the lowest-intensity intervention, which provided the patients with simple reminders and information. Brief education in addition to nurse support improves uptake of FOBT beyond enhanced usual care alone. Colorectal Cancer Screening Guideline 12

Davies and colleagues (2013) evaluated the effectiveness of interventions designed to promote CRC screening among 961 average-risk patients aged 50 85 years at 8 safety-net clinics in Louisiana. The study results showed that brief education in addition to nurse support improved uptake of FOBT beyond enhanced usual care alone. Lafata and colleagues (2014) showed that use of the 5A s (assess, advise, agree, assist, arrange) in the discussion between the physician and the patient may increase adherence to CRC screening. Management of diminutive colorectal polyps The literature search did not reveal any trial that compared the two strategies of Resect and discard versus Do not resect for managing the diminutive polyps detected on colonoscopy. Colorectal Cancer Screening Guideline 13

References Arora G, Mannalithara A, Singh G, et al. Risk of perforation from a colonoscopy in adults: a large population-based study. Gastrointest Endosc. 2009; 69:654-664. Atkin WS, Edwards R, Kralj-Hans I, et al; UK Flexible Sigmoidoscopy Trial Investigators. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010 May 8;375(9726):1624-1633. Aune D, Chan DS, Lau R, et al. Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. BMJ. 2011 Nov 10;343:d6617. doi: 10.1136/bmj.d6617. Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009 Jan 6;150(1):1-8. Blotière PO, Weill A, Ricordeau P, et al. Perforations and haemorrhages after colonoscopy in 2010: A study based on comprehensive French health insurance data (SNIIRAM). Clin Res Hepatol Gastroenterol. 2013 Nov 19. pii: S2210-7401(13)00224-6. Brink D, Barlow J, Bush K, Chaudhary N, et al. Colorectal Cancer Screening. Bloomington, MN: Institute for Clinical Systems Improvement. May 2012. https://www.icsi.org/guidelines more/catalog_guidelines_and_more/catalog_guidelines/catalog_preventi on screening_guidelines/colorectal/ Carroll C, Cooper K, Papaioannou D, Hind D, Pilgrim H, Tappenden P. Supplemental calcium in the chemoprevention of colorectal cancer: a systematic review and meta-analysis. Clin Ther. 2010 May;32(5):789-803. Cole BF, Logan RF, Halabi S, et al. Aspirin for the chemoprevention of colorectal adenomas: metaanalysis of the randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):256-266. de Haan MC, van Gelder RE, Graser A, Bipat S, Stoker J. Diagnostic value of CT-colonography as compared to colonoscopy in an asymptomatic screening population: a meta-analysis. Eur Radiol. 2011 Aug;21(8):1747-1763. Denis B, Gendre I, Sauleau EA, et al. Harms of colonoscopy in a colorectal cancer screening programme with faecal occult blood test: a population-based cohort study. Dig Liver Dis. 2013;45:474-480. Elmunzer BJ, Hayward RA, Schoenfeld PS, Saini SD, Deshpande A, Waljee AK. Effect of flexible sigmoidoscopy-based screening on incidence and mortality of colorectal cancer: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2012;9(12):e1001352. Green BB, Wang CY, Anderson ML, et al. An automated intervention with stepped increases in support to increase uptake of colorectal cancer screening: a randomized trial. Ann Intern Med. 2013 Mar 5;158(5 Pt 1):301-311. Hassan C, Giorgi Rossi P, Camilloni L, et al. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther. 2012 Nov; 36(10):929-940. Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev. 2007;(1):CD001216. Updated in 2011. Hoff G, Grotmol T, Skovlund E, Bretthauer M; Norwegian Colorectal Cancer Prevention Study Group. Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial. BMJ. 2009 May 29;338:b1846. Kaiser Permanente. Colorectal Cancer Screening National Clinical Practice Guideline. 2012 Kaiser Permanente Medical Care Program. Kaiser Permanente Northern California. Clinical Practice Guidelines: Colorectal Cancer Screening. October 2013. Keum N, Aune D, Greenwood DC, Ju W, Giovannucci EL. Calcium intake and colorectal cancer risk: Dose-response meta-analysis of prospective observational studies. Int J Cancer. 2014 Mar 13. doi: 10.1002/ijc.28840. [Epub ahead of print] Colorectal Cancer Screening Guideline 14

Ko CW, Riffle S, Michaels L, Morris C, et al. Serious complications within 30 days of screening and surveillance colonoscopy are uncommon. Clin Gastroenterol Hepatol. 2010;8:166-173. Lafata JE, Cooper G, Divine G, Oja-Tebbe N, Flocke SA. Patient-physician colorectal cancer screening discussion content and patients' use of colorectal cancer screening. Patient Educ Couns. 2014 Jan;94(1):76-82. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology. 2008 May 1;134(5):1570-1595. Littlejohn C, Hilton S, Macfarlane GJ, Phull P. Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as a screening method for the prevention of colorectal cancer. Br J Surg. 2012 Nov;99(11):1488-1500. Manser CN, Bachmann LM, Brunner J, Hunold F, Bauerfeind P, Marbet UA. Colonoscopy screening markedly reduces the occurrence of colon carcinomas and carcinoma-related death: a closed cohort study. Gastrointest Endosc. 2012 Jul;76(1):110-117. NCCN. National Comprehensive Cancer Network (NCCN) Guidelines: Clinical Practice Guidelines in Oncology: Colorectal Cancer Screening. Version 2.2013. 2013 NCCN. National Comprehensive Cancer Network (NCCN) Guidelines: Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment. Colorectal. Version 1.2014. 2014. Qaseem A, Denberg TD, Hopkins RH Jr, et al; Clinical Guidelines Committee of the American College of Physicians. Screening for colorectal cancer: a guidance statement from the American College of Physicians. Ann Intern Med. 2012 Mar 6;156(5):378-386. Available online at: http://annals.org/article.aspx?volume=156&page=378 Quintero E, Castells A, Bujanda L, et al; COLONPREV Study Investigators. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med. 2012 Feb 23;366(8):697-706. Schoen RE, Pinsky FP, Weissfeld JL, et al; PLCO Project Team. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012 Jun 21;366(25):2345-2357. Segnan N, Armaroli P, Bonelli L, et al; SCORE Working Group. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial--SCORE. J Natl Cancer Inst. 2011 Sep 7;103(24):1310-1322. USPSTF. Screening for Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. AHRQ Publication 08-05124-EF-3, October 2008. Agency for Healthcare Research and Quality, Rockville, MD. Vart G, Banzi R, Minozzi S. Comparing participation rates between immunochemical and guaiac faecal occult blood tests: a systematic review and meta-analysis. Prev Med. 2012 Aug;55(2):87-92. Warren JL, Kaunda CN, Marriott AB, et al. Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med. 2009 Jun 16;150(12):849-857. Ye X, Fu J, Yang Y, Chen S. Dose-risk and duration-risk relationships between aspirin and colorectal cancer: a meta-analysis of published cohort studies. PLoS One. 2013;8(2):e57578. Colorectal Cancer Screening Guideline 15

Guideline Development Process and Team Development Process To develop the Colorectal Cancer Screening Guideline, Group Health adapted recommendations from externally developed evidence-based guidelines and/or recommendations of organizations that establish community standards. The Group Health guideline team reviewed additional evidence in several areas. For details, see Evidence Summary and References. This edition of the guideline was approved for publication by the Guideline Oversight Group in May 2014. Team The Colorectal Cancer Screening Guideline development team included representatives from the following specialties: family medicine, gastroenterology, genetics, Group Health Research Institute, pathology, and residency. Clinician lead: David Grossman, MD, MPH, Medical Director, Population and Purchaser Strategy, grossman.d@ghc.org Guideline coordinator: Avra Cohen, MN, Clinical Improvement & Prevention, cohen.a@ghc.org Brandon Bartels, ARNP, Gastroenterology Amy Farrah, MD, Residency Andrew Feld, MD, Gastroenterology Bev Green, MD, Family Medicine, Group Health Research Institute Byron Hanson, MD, Family Practice Nancy Hanson, MS, Counselor, Genetics Robyn Mayfield, Patient Health Education Resources, Clinical Improvement & Prevention Carolyn Rutter, PhD, Group Health Research Institute Nadia Salama, MD, Clinical Epidemiologist, Clinical Improvement & Prevention Ann Stedronsky, Clinical Publications, Clinical Improvement & Prevention Lee-Ching Zhu, MD, Pathology Disclosure of conflict of interest Group Health Cooperative requires that team members participating on a guideline team disclose and resolve all potential conflicts of interest that arise from financial relationships between a guideline team member or guideline team member's spouse or partner and any commercial interests or proprietary entity that provides or produces health care related products and/or services relevant to the content of the guideline. Team members listed above have disclosed that their participation on the Colorectal Cancer Screening Guideline team includes no promotion of any commercial products or services, and that they have no relationships with commercial entities to report. Colorectal Cancer Screening Guideline 16