44 minute read
Seeing Is Believing: Why Colonoscopy S Remains the Gold Standard (CE/CME) R
Seeing is Believing
ACTIVITY DESCRIPTION
Routine screening colonoscopy with polypectomy is the most effective strategy for the prevention and early detection of colorectal cancer (CRC). Advantages include direct mucosal inspection of the entire colon and the ability to detect and remove precancerous polyps during a single session. Widespread use of this technique has contributed to an accelerating rate of decline in both the incidence and mortality of CRC from peak levels in the mid-1980s. Recently, noninvasive, home-based CRC detection tests have become available. One of the most important motivators for patient compliance with CRC screening guidelines is a recommendation from a primary care physician (PCP). The PCP has a unique opportunity to facilitate evidence-based and individualized screening in appropriate populations during regular checkups, in collaboration with specialists, and through appropriate referral and patient education. In this activity, participants will review the advantages and disadvantages of various CRC screening modalities and ways to maximize the effectiveness of the interdisciplinary team in delivering appropriate colonoscopy screening.
GOAL
The goal of this activity is to educate health care professionals about the use of appropriate CRC screening methods, including the limitations and advantages of both colonoscopic and noncolonoscopic approaches.
LEARNING OBJECTIVES
1. Review data supporting the importance of visualization via colonoscopy in the detection of CRC and precancerous polyps 2. Discuss the benefits and risks associated with the use of noncolonoscopic screening tests in the detection of CRC and precancerous polyps 3. Describe the role of the PCP in providing/referring for guideline-recommended CRC screening via colonoscopy
FACULTY Douglas K. Rex, MD, MACG, FASGE, MACP, AGAF
Distinguished Professor of Medicine Indiana University School of Medicine Chancellors Professor Indiana University Purdue University of Indianapolis Director of Endoscopy Indiana University Hospital Indianapolis, Indiana
David A. Johnson, MD, MACG, FASGE, MACP
Professor of Medicine Chief of Gastroenterology Eastern Virginia Medical School Norfolk, Virginia
Bill H. McCarberg, MD, FABM
Kaiser Permanente San Diego (retired) Adjunct Assistant Clinical Professor University of California San Diego, California
INTENDED AUDIENCES
The intended audience for this activity comprises gastroenterologists and other health care professionals interested in CRC screening, colonoscopy, and appropriate bowel preparation.
ACCREDITATION AND CREDIT DESIGNATION STATEMENTS
Physician Accreditation Statement This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group and Applied Clinical Education. Global Education Group is accredited by the ACCME to provide continuing medical education for physicians. Physician Credit Designation Global Education Group designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nursing Continuing Education Global Education Group is accredited with distinction as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. This educational activity for 1.0 contact hour is provided by Global Education Group. Nurses should claim only the credit commensurate with the extent of their participation in the activity. FEES: Free
METHOD OF PARTICIPATION
To receive CME credit, participants should read the preamble, participate in the activity, and complete the post-test and activity evaluation at www.cmezone.com/CU201. CME certificates will be made available immediately upon successful completion.
DISCLOSURE OF CONFLICTS OF INTEREST
Global Education Group requires instructors, planners, managers and other individuals and their spouse/life partner who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations. The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this activity: • David A. Johnson, MD, MACG, FASGE, MACP: Aries Pharmaceuticals, Avrio Health, CRH Medical, Medscape/ WebMD (consultant/independent contractor); CRH Medical (stock shareholder) • Bill H. McCarberg, MD, FABM: Adapt, Scilex (speakers bureaus); Collegium, Johnson and Johnson, Sellas Life Sciences (stock shareholder); Averitas, Lilly, Scilex (consultant/independent contractor)
• Douglas K. Rex, MD, MACG, FASGE, MACP, AGAF: Aries Pharmaceutical, Boston Scientific, Braintree Laboratories, Endokey, GI Supply, Lumendi Ltd, Medtronic, Norgine, Olympus Corporation (consultant/independent contractor); EndoAid Ltd, Erbe USA Inc, Olympus Corporation, Medivators Inc (grant/research support); Satisfai Health (ownership) The planners and managers reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: • Kathleen Wildasin: Nothing to disclose • Jennifer Kulpa: Nothing to disclose • Andrea Funk: Nothing to disclose • Lindsay Borvansky: Nothing to disclose • Ashley Marostica, RN, MSN: Nothing to disclose
DISCLOSURE OF UNLABELED USE
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Global and ACE do not recommend the use of any agent outside of the labeled indications. The opinions expressed in this activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
DISCLAIMER
Participants have an implied responsibility to use newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or courses of diagnosis or treatment discussed should not be used by clinicians without evaluation of patient conditions, contraindications, applicable manufacturer’s product information, and the recommendations of other authorities.
GLOBAL CONTACT INFORMATION
For information about the accreditation of this program, please contact Global Education Group at 303-395-1782 or cme@globaleducationgroup.com.
Seeing Is Believing: Why Colonoscopy Remains the Gold Standard Proceedings from a live event presented October 28, 2019
Introduction
Colorectal cancer (CRC) is the third most common cancer in the United States and the third leading cause of cancer death in US men and women.1,2 Five-year survival is greatly affected by stage at diagnosis, ranging from 90% when localized to only 14% with distant metastases,3 underscoring the importance of early detection and treatment. Efforts to prevent CRC via screening colonoscopy have led to declines in incidence of approximately 3% per year during the last decade,2 and most professional guidelines recommend colonoscopy every 10 years in average-risk individuals starting at 50 years of age.4 Compliance with this guidance varies greatly by region in the United States, from a high of 76% in Massachusetts to a low of 58% in Wyoming.2,5
The advantages of colonoscopy include the ability to detect and remove precancerous lesions—including adenomas, the precursor to about 70% of CRCs,4 and serrated lesions—in the same procedure. Numerous improvements in colonoscopy have occurred over the past few decades, including the introduction of high-definition scopes, the development of techniques
CRC Screening Tests: The PCP Perspective
Bill H. McCarberg, MD, FABM
Approaches to Screening
Most national organizations, such as the US Preventive Services Task Force (USPSTF) and American Cancer Society (ACS), provide information about the various CRC screening tests without a ranking. In a busy primary care practice, this leaves the decision about which test to recommend up to the provider, who may be inclined to focus on the test that raises the fewest questions or issues from the patient.
In contrast, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer—which includes the American Gastroenterological Association (AGA), American Society for Gastrointestinal Endoscopy (ASGE), and American College of Gastroenterology (ACG)—stratifies CRC screening
Table 1. US Multi-Society Task Force–Recommended
CRC Screening Tests4 Tier Test/Frequency Frequency
to resect lesions throughout the entire colon, and the establishment of quality indicators. At issue for some patients is bowel cleansing in preparation for colonoscopy, which is an acknowledged challenge. Recently, noncolonoscopic screening modalities have been introduced and are being promoted to patients and physicians alike as screening alternatives to colonoscopy that do not require bowel preparation.
This presentation covered approaches to CRC screening, including data for the benefits and risks of available screening tests; the important role that the primary care physician (PCP) plays in recommending the appropriate test for each patient; and strategies for maximizing the effectiveness of colonoscopy. Case studies were incorporated to elucidate key points. In addition, the session sought to gather feedback from attendees on effective messaging around this topic, namely the following: • Are you messaging your own PCPs about the value of screening colonoscopy? • What is your message about screening colonoscopy? About other
screening modalities?
1
Colonoscopy Every 10 y
2
3
FIT Every 1 y CT colonography Every 5 y FIT-fecal DNA Every 3 y Flexible sigmoidoscopy Every 10 or 5 y Capsule colonoscopy Every 5 y tests into 3 tiers based on performance features, costs, and practical considerations (Table 1).4 This can help streamline the conversation.
The setting in which the CRC screening process begins is important. Organized screening refers to a system-wide, organized approach in which screening is offered to an employee population or members of a health care plan, whereas opportunistic screening refers to screening that takes place during an interaction between a patient and health care provider in an office-based setting. Organized screening is dominated by fecal immunochemical testing (FIT); however, colonoscopy is often available in this setting as well.4 In the United States, most CRC screening occurs in the opportunistic setting and involves colonoscopy, FIT, or FITfecal DNA testing.
Within the opportunistic setting, 3 different approaches can be used to offer screening to patients.4 The sequential approach involves first offering the provider’s preferred screening test (colonoscopy); if the patient declines the first option, a second test (FIT) is then offered. In the riskstratified approach, colonoscopy is offered to patients predicted to be at high risk for precancerous lesions based on factors such as older age, male gender, smoking, diabetes, and obesity; and other screening tests are offered to patients predicted to be at a lower risk. In the multiple-options approach, the benefits, risks, and costs of 2 or more screening options are discussed. Recent qualitative studies have shown that offering more than 2 options does not improve adherence but actually leads to confusion and nonadherence. In a cross-sectional study of 1,707 survey respondents, those who discussed more than 2 options for CRC screening with their physicians were 1.6 times more likely to be confused than those who discussed 1 option, and those who reported confusion were 1.8 times more likely to be nonadherent to screening than those who did not.6
It is important to acknowledge the numerous barriers to CRC screening.7,8 Health-system barriers include lack of insurance or inadequate access to payment resources, lack of recommendation from a PCP to undergo screening, and lack of language interpretation services. Personal/cultural barriers include lack of knowledge or misconceptions about screening, poor understanding of bowel preparation instructions, distrust of the medical system or a fatalistic attitude about cancer, lack of transportation or inability to take time off from work, and embarrassment or fear of the procedure.
Overcoming these barriers requires physician intervention, particularly on the part of the PCP. A recent review found that among adults who were not current with CRC testing despite having a PCP visit within the previous year, 90% cited lack of physician recommendation as the reason for lack of testing.8 This underscores the key role of a PCP recommendation in improving health-related behaviors. In a 2008 Cochrane Review of 41 trials, including more than 31,000 smokers, the most common setting for delivery of smoking cessation advice was primary care.9 Pooled data showed a significant increase in the rate of quitting among patients who received a brief intervention from a PCP. The authors concluded that, assuming an unassisted quit rate of 2% to 3%, the PCP can increase quitting by a further 1% to 3%.
“PCPs have many demands on their time and often don’t make the necessary recommendations for colonoscopy. Sometimes there is a note in the patient’s chart that goes unnoticed, and sometimes busy PCPs simply forget. What is important to acknowledge, however, is that when patients do not undergo colonoscopy at the appropriate time, it’s most often because the provider hasn’t informed them that it needs to be done. It’s very important that PCPs get the message across.
In addition, readers may not be aware of the effect that gastroenterologists can have on PCPs by just advising them to mention and encourage screening. PCPs are always interested in doing the best for their patients. If colonoscopy is the best test as judged by providers opting for this test for themselves, then the providers should encourage this same best test for patients, even if they encounter resistance.” —Bill H. McCarberg, MD, FABM
Colonoscopy
Colonoscopy provides direct visual examination of the entire colon as well as the removal of precancerous lesions. This procedure remains the gold standard for CRC screening and is the reference used to evaluate all other screening methods.10 Colonoscopy confers the longestlasting protection compared with other screening options. In fact, the protective effect of colonoscopy screening corresponds to an 89% reduction in CRC incidence (Table 2).12-16 Another benefit of colonoscopy is that lesions detected during the procedure can be removed immediately. A cost-effectiveness analysis also found that colonoscopy performed every 10 years is less costly and/or more effective than other CRC screening strategies commonly used in the United States.11 Disadvantages of colonoscopy include the need for complete bowel cleansing; the potential occurrence of procedural adverse events (eg, perforation); the need for and risks associated with anesthesia; operator dependence; and schedule interruptions due to procedural preparations.10,17
Fecal Immunochemical Testing
FIT measures human hemoglobin (Hb) in stool as a marker for colon cancer. The chief advantage of FIT is that it is noninvasive, eliminating the need for bowel preparation. Instead, the patient provides a stool sample via a mail-in collection kit; this is more cost-effective than other methods of screening. A meta-analysis of 19 trials assessing the diagnostic performance of FIT for CRC detection in average-risk, asymptomatic individuals reported the sensitivity and specificity to be 79% and 94%, respectively.18 FIT is more effective at detecting cancers than polyps, but in a metaanalysis of 12 studies (N=6,204), the sensitivity of FIT for advanced neoplasia was just 48%.19
In the United States, FIT is reported as positive or negative based on a cutoff of 20 mcg Hb/g feces.20 Recent studies have examined the association between fecal Hb concentrations below the FIT cutoff value and the later development of colorectal advanced neoplasia (AN). In one study of 9,561 average-risk individuals aged 50 to 74 years, those with concentrations of 8 to 10 mcg Hb/g had a higher cumulative incidence of AN versus those with a concentration of 0 mcg Hb/g after 8 years of follow-up (33% vs 5%; P<0.001).21 Participants with 2 consecutive Hb concentrations of 8 mcg Hb/g had a 14-fold increase in risk for AN compared with those who had 2 consecutive concentrations of 0 mcg Hb/g (P<0.001).
The chief disadvantage of FIT is the necessity of repeating it annually. This can be challenging in the opportunistic setting, as it lacks the
Table 2. Colonoscopy in the Literature11-15
Author/Study Year N Design
Incidence, % Mortality, %
National Polyp Study11,12
Kahl et al13
Jacob et al14
Pan et al15
1993 1,418 vs Mayo Clinic, St Mark’s, SEER cohorts 79-90 53 2009 715 vs SEER data 67 65
2012 1,089,998 Instrumental variable analysis 48 81 2016 1,499,521 Meta-analysis of 11 studies 89 61
structure and systematic navigation tools of the organized screening setting. On their own, only 1 in 5 patients gets an annual physical, for example.22 A recent retrospective cohort analysis of 1,122,645 patients found that only 14% of those scheduled for annual FIT actually completed the test in 4 of 5 years.23 In addition, FIT does not detect serrated lesions, and patients with positive results must undergo colonoscopy, for which insurance coverage likely will not be provided.
FIT-Fecal DNA Testing
The FIT-fecal DNA test screens for occult blood measured by immunoassay as well as the presence of known DNA alterations in tumor cells during colorectal carcinogenesis that are shed into the stool.10,24 FIT-fecal DNA testing has been shown to have a 92% sensitivity for cancer and is more effective than FIT in detecting serrated lesions.25 The test is done at home, requires only a single stool sample, and does not require time off from work.24 The FDA has approved the use of FIT-fecal DNA testing at 3-year intervals for average-risk individuals aged 45 years and older. In the pivotal trial, a relatively high rate of false-positive results was noted, at 13.4%. Other disadvantages of FIT-fecal DNA testing are as follows: • It is less effective and less cost-effective than both FIT and colonoscopy. • Its specificity is lower than that of FIT (88% vs 95%, respectively) and decreases with age. • Long-term data are not available. • DNA testing adds limited sensitivity, increases the rate of false positives, and adds substantial cost. • Positive test results require follow-up colonoscopy with bowel preparation.
Flexible Sigmoidoscopy
Flexible sigmoidoscopy provides visualization of the sigmoid colon. Data from several randomized controlled trials and meta-analyses have shown that flexible sigmoidoscopy reduces CRC incidence and
Discounted Mean QALYs per Person
mortality.26-29 Other advantages include limited bowel preparation (ie, pre-procedure enema only), lack of a sedation requirement, and lower risk and cost versus colonoscopy. At present, however, this test is unpopular in the United States and rarely used for CRC screening. Disadvantages include the inability to examine the proximal colon; concerns about the lack of quality standards and limited availability; patient pain/discomfort (ie, low patient satisfaction); the need for further endoscopic examination if findings are positive; and the potential for additional out-of-pocket expenses associated with follow-up procedures.10,17
Of note, an indirect comparison of data from observational studies suggested a 40% to 60% lower risk for incident CRC and death from CRC after screening colonoscopy versus flexible sigmoidoscopy.29
Computed Tomographic (CT) Colonography
CT colonography (also known as virtual colonoscopy) produces 2- or 3-dimensional images of the colon. It is noninvasive, does not require sedation, and has a lower risk for perforation than colonoscopy.10,17,30 In a meta-analysis of 33 studies (N=6,393), the sensitivity and specificity of CT colonography were found to be 70% and 86%.31 Polyp detection rates varied by size, with poor detection of polyps smaller than 6 mm (48%). In addition, CT colonography is associated with radiation exposure; the need for full bowel cleansing; poor sensitivity for flat or serrated lesions; the potential for extracolonic findings that may require further investigation; and requirement of follow-up colonoscopy—including a second bowel preparation—in cases with positive findings.10,17,30
Capsule Colonoscopy
Capsule colonoscopy is an imaging capsule approved by the FDA in 2014 for use in patients who are unable to complete a colonoscopy, refuse to undergo a colonoscopy, or are not candidates for colonoscopy or sedation. The advantages of capsule colonoscopy include min-
6,000 –
Discounted Mean Cost per Person, $
5,000 –
4,000 –
3,000 –
2,000 –
1,000 –
0 –ı 18.86
ı ı ı ı 18.68 18.70 18.72 18.74 imal patient discomfort and minimal interference with daily activities.
ı 18.76 No screening FIT q2ya MT-sDNA q3ya FIT yearlya FIT q2yb MT-sDNA q3yb Colonoscopy q10yb FIT yearlyb
Figure 1. Effectiveness (discounted QALYs per person) and cost (discounted dollars per person) for screening strategies.
FIT with 100% consistent screening participation and without additional patient support costs was cost-saving compared with no screening. MT-sDNA testing achieved effectiveness similar to the other strategies given the same levels of patient participation, but it was more costly. Participation rates of 50% consistent screening and 27% intermittent screening are representative of successful organized screening programs, and the results for FIT with these participation rates include patient support costs of $153 per testing cycle.
FIT, fecal immunochemical testing; MT-sDNA, multi-target stool DNA; QALY, quality-adjusted life-year. a 50% consistent, 27% intermittent screening. b 100% consistent. Reprinted from Gastroenterology, vol 151(3), Ladabaum U, Mannalithara A, Comparative effectiveness and cost effectiveness of a multitarget stool DNA test to screen for colorectal neoplasia, pages 427-439.e6, Copyright 2016, with permission from Elsevier.
A 2015 study of 695 average-risk patients 50 to 75 years of age demonstrated 88% sensitivity and 82% specificity for identifying adenomas of 6 mm or larger.32 Similar to CT colonography, however, positive findings require follow-up colonoscopy and repeat bowel preparation. At present, capsule colonoscopy is not approved for CRC screening and usually is not covered by insurance.33
Cost-Effectiveness of CRC Screening Strategies
A recent study comparing the cost-effectiveness of available CRC screening strategies found that FIT-fecal DNA was only cost-effective versus no screening and not cost-effective versus the other 5 strategies.34 In the study, 3 microsimulation models were used to simulate previously unscreened 65-year-old individuals who were screened for CRC with 1 of 6 Centers for Medicare & Medicaid Services–reimbursed screening strategies: 1) fecal occult blood test every year; 2) FIT every year; 3) flexible sigmoidoscopy every 5 years; 4) flexible sigmoidoscopy every 10 years plus FIT every year; 5) colonoscopy every 10 years; or 6) FIT-fecal DNA every 3 years. The main outcome measures were discounted life-years gained, lifetime costs, threshold reimbursement, and threshold adherence. At its 2017 reimbursement rate, FIT-fecal DNA testing was found to be the most costly of the 6 strategies; furthermore, if adherence was 30% higher with FIT-fecal DNA than with other strategies, it would still not be a costeffective option.
In another analysis, yearly FIT (without additional patient support costs) yielded the highest mean QALYs per person, followed by screening colonoscopy, FIT-fecal DNA testing every 3 years, and FIT every 2 years (Figure 1).35 Yearly FIT and colonoscopy every 10 years were more effective and less costly than FIT-fecal DNA testing every 3 years, when participation rates were equal across strategies.
Conclusion
Primary care physicians play an important role in CRC screening and thus must be knowledgeable about barriers and approaches to screening in an opportunistic setting, the ranking of various available tests based on benefits and risks, and comparative cost-effectiveness across the range of CRC screening strategies.
Common Scenarios in CRC Prevention
Douglas K. Rex, MD, MACG, FASGE, MACP, AGAF
Introduction
Dr. Rex presented scenarios commonly encountered in clinical practice and initiated a discussion about how best to evaluate the individuals described. Cases described: • Rectal bleeding in a 29-year-old man • Screening in 45- to 49-year-olds • Positive FIT and refusal of colonoscopy • Positive FIT and negative colonoscopy • Positive FIT-fecal DNA and negative colonoscopy • Positive FIT 2 years after negative colonoscopy
Case Study 1: Evaluation of Rectal Bleeding
Presentation
A 29-year-old man presents with rectal bleeding. What type of evaluation is most appropriate?
Commentary
Rectal bleeding is the most predictive symptom of CRC. Bleeding symptoms, such as hematochezia, melena with a negative upper endoscopy, iron deficiency anemia, and a positive fecal occult blood test, also have positive predictive values between 2% and 12% for cancer. Other change in stool shape, and abdominal pain—do not have predictive value for CRC absent evidence of bleeding.
A central area of medicolegal risk for PCPs is delaying the diagnosis of colon cancer by attributing rectal bleeding to hemorrhoids or some anal cause and not evaluating it. The details regarding bleeding are often poorly documented in a patient’s medical record; however, the record should describe the color of the blood, the frequency of bleeding, and the duration of bleeding. Some experts will advise that any blood, including blood on the toilet paper, is an indication for colonoscopy; however, if the blood is only on the paper, it is reliably from the anus. The source is less clear if the blood is in the toilet bowl, in which case, the issue becomes whether to perform colonoscopy, anoscopy, or flexible sigmoidoscopy. Traditionally, if there is blood in the toilet bowl, most clinicians would recommend colonoscopy even in young patients based on the rising incidence of colon, and particularly rectal, cancer in individuals under the age of 55 years in the United States. Cost also plays a role in the decision-making process.
Takeaway
In a relatively young patient presenting with rectal bleeding, the cause of bleeding should be identified and treated. If a test other than colonoscopy is used, the patient should be treated and followed to ensure resolution of bleeding.
Case Study 2
Presentation symptoms that patients may worry about—change in bowel habits,
A 47-year-old white woman with no known family history of CRC and no symptoms is seeking CRC screening. She states that her father had a colonoscopy and may have had polyps; however, she does not know whether they were advanced polyps. Should this patient undergo colonoscopy?
Commentary
Both family history and age should be considered in deciding whether screening is appropriate for this relatively young, asymptomatic patient. CRC screening recommendations based on family history are shown in Figure 2. 4
The current guidelines vary in their recommendations for the age at which CRC screening should start.36 For example, the USPSTF recommends
starting at 50 years in everyone,37 whereas the ACS recommends starting at 45 years of age in everyone.38 The MSTF recommends starting at 50 years of age in average-risk cases and at 40, or 10 years younger than the age at which the youngest affected relative was diagnosed, for high-risk cases.4 The MSTF recommends starting at age 45 in black patients.4
CRC Mortality Trends
In the past 15 to 20 years, CRC mortality rates have increased in white and decreased in black people younger than 50 years of age. The ACG was the first group to recommend starting CRC screening at 45 years of age in black people; however, the mortality rates for white and black individuals younger than 50 years have since converged.
CRC Incidence Trends
The incidence of colon cancer began to increase circa 1980 in individuals aged 20 to 29 years, with some experts speculating that the introduction of processed foods in the 1970s or changes in the microbiome may have been the source of the increase. Of note, from the mid-1980s through 2013, the rate of colon cancer incidence increased by 2.4% per year in that age group. Similarly, in the mid-1990s, the rate also began increasing in adults aged 50 to 54 years (0.5% per year).39 The increase in colon cancer incidence in individuals younger than 50 years was confined to tumors in the distal colon, with the exception of individuals aged 40 to 49 years, in whom the incidence also increased for tumors in the proximal colon.39 Incidence in the 50- to 54-year-old and 55- to 59-year-old cohorts now is very similar for colon cancer (only 12.4% lower for younger patients) and virtually equal for rectal cancer.39
The relative risk for CRC in individuals born in 1990 has increased dramatically versus those born in 1950—2.4-fold for colon cancer and more than 4-fold for rectal cancer (Figure 3).39 In addition, the percentage of all rectal cancers that occur in people under the age of 55 years has nearly doubled between 1990 and 2013, from 14.6% to 29.2%. About
Single FDR with CRC or advanced adenoma diagnosed at <60 y Multiple FDRs with CRC or advanced adenomas at any age Single FDR with CRC or advanced adenoma diagnosed at >60 y
Begin screening at 40 y or 10 y before age at diagnosis of youngest affected relative Begin screening at 40 y
Colonoscopy q5y Tests and intervals as in average-risk patients
50% of all cancers that occur in individuals younger than 50 years in the United States occur in the 45- to 49-year-old age group.40
Among 45- to 49-year-olds, 7,000 individuals were diagnosed with CRC in 2017 and 1,800 died of the disease.17 The actual burden in terms of all life-years lost due to premature CRC death is now similar, at 13% for those aged 50 to 54 years and 10% for those aged 45 to 49 years.17
“There is fairly good evidence to suggest that the increased risk for CRC in people younger than the age of 50 years is real. Between 2000 and 2013, the rate of colonoscopy in 40- to 49-year-olds more than doubled, from 6.4% to 13.6%.41 These data raise the question of whether the increased incidence is the result of an increase in screening.42 A real increased risk for CRC in young persons is supported by available evidence. First, the relative risk is higher in younger cohorts, that is, 20- to 29-yearolds have a greater increase in relative risk than 30- to 39-yearolds and 40- to 49-year-olds.39 Second, the increased incidence rates have been observed in both early- and late-stage cancers.39 Finally, CRC mortality rates are also increasing.43
In terms of screening 45- to 49-year-olds, risk stratification could be quite valuable. It would make sense to use colonoscopy in a 47-year-old man who is obese, diabetic, and a cigarette smoker. That person is almost certainly a better candidate for screening colonoscopy than a 47-year-old, thin, vegan, marathon-running female.” —Douglas K. Rex, MD, MACG, FASGE, MACP, AGAF
5
Individuals Born in 1990 vs 1950
35
Rectal Cancers in Those Aged <55 y
4
Incidence Rate Ratio
3
2
1 2.4 4.33 30
25
Percentage
20
15
10
5 14.6 29.2
0
CRC Rectal cancer
0
1990 2013
Figure 3. Colon and rectal cancer incidence data.39
Cost-Effectiveness of Screening Younger Individuals
A recent study estimating the cost-effectiveness of initiating CRC screening in average-risk younger individuals found that colonoscopy initiation at 45 years of age versus 50 years of age per 1,000 individuals screened averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), and cost $33,900 per QALY gained.44 The initiation of FIT at 45 years of age instead of at versus 50 cost $7,700 per QALY gained. The study also found that although CRC screening initiation at 45 years of age would likely be cost-effective, a greater benefit at a lower cost could potentially be attained by increasing CRC screening rates in unscreened older individuals and those at higher risk. In the study, aerodigestive cancers developed in 5 patients in the 10 years and not perform FIT-fecal DNA testing again.
At present, about 22 million Americans are between the ages of 45 to 49 years, so it is reasonable to ask whether CRC screening in this age group would shift resources. Indeed, the cost of CRC screening would be substantial—$10.4 billion over 5 years—but those being screened would not all present simultaneously. Furthermore, there is no evidence that colonoscopy resources have been exhausted in the United States,45 and screening rates have leveled off in individuals at least 50 years of age.
Takeaway
Colonoscopy screening in individuals aged 45 to 49 years is costeffective; however, a risk-stratified, organized approach should be considered to control costs.
Case Study 3 Presentation
A 52-year-old woman with positive FIT results refuses colonoscopy. What should be done next?
Commentary
According to USMSTF recommendations on quality in FIT programs, 80% of patients with positive FIT results should undergo a diagnostic colonoscopy.46 Unfortunately, a diagnostic colonoscopy requires a copay, which is often a factor in patient decision making.
Takeaway
A reasonable approach with a patient who refused colonoscopy despite a positive FIT result would be to document the discussion and warn the patient of her risk for death from failing to undergo colonoscopy.
Case Study 4 Presentation
A 54-year-old man has positive FIT results and a normal colonoscopy. He has no symptoms, and his Hb level is within normal limits. Should he FIT and FIT-fecal DNA testing should not be recommended to
undergo additional testing?
Commentary
No further evaluation is needed. Although some clinicians might perform an upper endoscopy, current evidence suggests that such testing Takeaway
Patients with negative colonoscopy results require no further screening for at least 5 or 10 years. Some clinicians might prefer to resume FIT screening after 5 years.
Case Study 5 Presentation
A 54-year-old man has positive FIT-fecal DNA results and a normal colonoscopy. He has no symptoms, and his Hb level is within normal limits.
Commentary
In such a scenario, no other tests (ie, upper endoscopy, small bowel evaluation, CT scans) are necessary. This approach is supported by a recent cohort study (N=1,216), in which patients with negative findings on high-quality colonoscopies had low incidence of aerodigestive cancers, regardless of discordant or concordant findings from multitarget stool DNA tests, after a median of 5.3 years of follow-up.47 discordant group and 11 patients in the concordant group (adjusted risk ratio, 2.2; P=0.151). Furthermore, the incidence of aerodigestive cancers was lower in the concordant group than expected based on Surveillance, Epidemiology, and End Results Program data (risk ratio, 0.4; P=0.0008).
Takeaway
In a patient with positive FIT-fecal DNA but discordant colonoscopy results, a reasonable approach would be to stop screening for 5 or
Case Study 6 Presentation
A 72-year-old man has positive FIT results 2 years after a negative colonoscopy. What should be recommended to him?
Commentary
A positive FIT or FIT-fecal DNA test result is an indication for colonoscopy. However, many patients who have a positive FIT result will undergo a second FIT to confirm the result, and if the second FIT is negative, may decide not to follow through with the colonoscopy. An important message for PCPs is to avoid CRC screening during the interval after colonoscopy in order to avoid having to refer patients for further testing.
Takeaway
has a high yield for benign findings, but not for cancer. patients during the guideline-recommended interval after a normal colonoscopy, as this can be confusing and expensive if the patient has a false-positive result on one of the home tests.
Improving the Performance of Colonoscopy
David A. Johnson, MD, MACG, FASGE, MACP
Colonoscopy Preparation
The optimal effectiveness of colonoscopy requires patient acceptance of both the procedure and the preparation.48 Inadequate bowel preparation, which occurs in 20% to 25% of patients in some series, leads to failed procedures, the need for repeat procedures, failed lesion detection, procedural adverse events, and patient no-shows. Furthermore, a failed screening colonoscopy due to inadequate bowel preparation is an indicator for repeat colonoscopy within 1 year—something most insurance companies will not cover.
Several bowel preparations with different formulations and dosages are available and should be individualized to help facilitate tolerability and minimize no-shows on the day of the procedure (Table 3).49-58 The most recent introductions have aimed to reduce the volume of fluid the patient must consume and improve the taste of the formula, while maintaining safety.
Split Dosing for Bowel Preparation
Split dosing, whereby the patient consumes the bowel preparation product in 2 doses—the first on the day before the colonoscopy and the second the morning of the colonoscopy—is endorsed as the standard of care over day-before dosing, in which the patient consumes the entire dose of bowel preparation the day before the procedure.48,59 The split doses are not necessarily equal in volume or composition; however, the morning dose is particularly important because it cleans out any remaining fecal material and especially the small bowel chyme that continues to enter the right colon. Of note, the same bowel preparation regimen can be used in patients planning a colonoscopy on the same day as the preparation (ie, an afternoon colonoscopy).
Split dosing of bowel preparations is associated with higher adenoma detection rates (ADRs) than day-before dosing.60,61 In a randomized controlled trial in 690 patients who received a low-volume 2-L polyethylene glycol-ascorbate solution as preparation for a colonoscopy after positive FIT findings, a split-dose regimen increased the ADR for at least 1 adenoma by 22% and for at least 1 advanced adenoma by 35% over a completed day-before regimen (Figure 4).60,61 Split dosing was also superior to day-before dosing in the detection of sessile serrated polyps (8% vs 4%), the achievement of overall excellent colon cleansing (80% vs 55%), compliance (92% of patients vs 86% able to consume the full preparation), and tolerability reports (62% vs 50% described “no distress” with solution intake).60
Although the preponderance of evidence and guidelines from the ACG and USMSTF support split dosing,48 the adoption of this regimen remains suboptimal due to several identified barriers, including the timing and scheduling of anesthesia, difficulties associated with morning colonoscopies relative to eating, and the potential for fecal incontinence.61
Quality Indicators for Colonoscopy
National guidelines recommend that patients ask prospective colonoscopists relevant questions pertaining to ADR, cecal intubation rate, and split-dose bowel preparations before colonoscopy to help enhance a high-quality examination (Table 4).4
A study examining quality indicators for colonoscopy found that ADR is an independent predictor of the risk for interval CRC after screening colonoscopy (Figure 5).62 In the study, which collected data from 186 endoscopists involved in a colonoscopy-based CRC screening program (N=45,026), a total of 42 interval CRC cancers were identified during a period of 188,788 person-years. A higher ADR was found to be significantly associated with a lower risk for interval CRC (P=0.008). Specifically, the hazard ratios for ADRs of less than 11.0%, 11.0% to 14.9%, and 15.0% to 19.9% were 10.94, 10.75, and 12.50, respectively, compared with ADRs of at least 20% (P=0.02 for all comparisons). Of interest, the rate of cecal intubation was not significantly associated with the risk for interval CRC (P=0.50).
Another study—this one evaluating 314,872 colonoscopies performed by 136 gastroenterologists—found that ADR was inversely associated with the risk for interval CRC, advanced-stage interval CRC, and fatal interval CRC.63 In the study, ADR was highly variable among
Table 3. Available Bowel Preparations49-58
Active Ingredient(s) Dosage Form(s) Brand Approved
PEG-ELS49-52
PEG-ELS, AA53
Sodium phosphate54
Oral sulfate solution55
Sodium picosulfate, magnesium oxide, citric acid56,57
PEG-ELS, sodium ascorbate58
Powder for reconstitution (4 L) Colyte, GoLytely, others 1980s Powder for reconstitution, SF (4 L) NuLYTELY, Trilyte, others 1990s Powder for reconstitution (2 L) MoviPrep 2006 Liquid, tablet OsmoPrep 2006 Liquid concentrate for dilution Suprep 2010 Powder for reconstitution Prepopik 2012 Oral solution Clenpiq 2017 Powder for reconstitution Plenvu 2018
gastroenterologists, ranging from 7.4% to 52.5%. During follow-up, 712 interval colorectal adenocarcinomas were identified, including 255 advanced-stage cancers; in addition, 147 patients died from interval CRC. In patients whose gastroenterologists had ADRs in the highest versus lowest quintiles, the adjusted hazard ratios for any interval cancer, advanced-stage interval CRC, and fatal interval CRC were 0.52, 0.43, and 0.38, respectively. Of note, each 1.0% increase in ADR was associated with a 3.0% decrease in the risk for CRC and a 5% decrease in the risk for a fatal interval CRC.
“If we move the quality needle for colonoscopy by even small steps, we’re making demonstrable changes in strategic end points. Any improvement in colon cancer and colon cancer deaths makes a difference, which is the reason society guidelines have emphasized that colonoscopy is a tier-1 test. It’s the ‘gold standard’ test that can prevent, detect, and treat colon cancer all in the same procedure. Ideally the best purpose of CRC screening is prevention of cancer via recognition and removal of precancerous lesions.” —David A. Johnson, MD, MACG, FASGE, MACP
Quality Colonoscopy: PCP Responsibility
The quality and safety of colonoscopy vary among clinicians, even among those with extensive training, experience, and certification.64 It is therefore critical that PCPs are able to identify clinicians who meet highquality standards to facilitate appropriate referrals. To that end, PCPs should rely on the actual performance of colonoscopy, not only the training and specialty of the clinicians who perform the procedure.
A consensus statement from the Quality Assurance Task Group, a working group of the National Colorectal Cancer Roundtable, identified 1) photographs of the end of the colon, including the appendiceal orifice dence and anecdotal experience now indicate that the overwhelming per-
several indicators that PCPs can utilize to evaluate the quality of colonoscopy services.65 The main elements of quality recommended by the working group include a complete colonoscopy report, technical competence, and a safe setting for the procedure.
The colonoscopy report should contain descriptions of 5 major elements: 1) depth of insertion, 2) quality of the bowel preparation, tions for follow-up and/or surveillance unless pathology is needed to
Table 4. Questions Patients Should Ask Prospective Colonoscopists4
Question Expectation
What is your adenoma detection rate?
What is your cecal intubation rate?
Do you use split-dosing of bowel preparations?
≥25% overall
≥30% for men and ≥20% for women
≥95% for screening colonoscopies ≥90% overall
At least half the preparation should be ingested on the day of the colonoscopy determine follow-up schedule. The assessment of technical competence should focus on the ADR and cecal intubation rate achieved by the endoscopist and whether these rates meet quality standards. Characteristics of a safe colonoscopy setting include adequate disinfecting/cleaning of equipment, well-maintained equipment, well-trained staff and endoscopist, and the ability to react to emergency situations (eg, bleeding, perforation, cardiovascular events) that could potentially arise during the procedure.
National guidelines recommend that the colonoscopy report include and ileocecal valve/terminal ileum, to demonstrate that the full extent of the colon was examined; and 2) a description of the bowel preparation quality, which must be adequate to ensure an effective examination.4
Management of Large Colon Polyps
In the United States, more than 50% of segmental colon resections are performed on benign colorectal lesions that may not have required surgery. These often include polyps that are located in the right colon, non-pedunculated in shape, or large in size.65 However, considerable evi3) patient tolerance of the procedure, 4) polyps, and 5) recommenda-
centage of large colon polyps are amenable to endoscopic resection by experts. A recent single-center study (N=82) found, for example, that 74% of patients with benign difficult colorectal lesions referred for surgical resection were successfully treated endoscopically.66
Costs and complications also factor into the decision of how to manage large polyps. A prospective, observational, multicenter study of consecutive patients with large, laterally spreading colorectal lesions (N=1,353) found that endoscopic mucosal resection was significantly more costeffective than surgery and associated with a shorter hospital length of stay (LOS; Figure 6).67
60
50
40 Patients, % 30 20
10 P=0.002
53
41
Detection rates
P=0.047
26
20
0
Adenoma Advanced adenoma
Split-dose Prior-PM
P=0.053
8 4
Sessile serrated polyp
13
12
CRC Hazard Ratio
Cost per patient AUD $, thousands EMR
11
10 10.94
10.75 12.5
9
<11% 11%-14% 15%-19.9%
ADR
Figure 5. ADR and risk for interval cancers in a Polish screening database.62
ADR, adenoma detection rate; CRC, colorectal cancer.
A recent systematic review of 26 studies involving 139,897 patients found substantial postoperative morbidity and mortality after surgical resection for benign colon polyps.65 The 1-month pooled complication rate was 24%; the anastomotic leak rate ranged from 0.3% to 8.7%; the mean hospital LOS was 5.1 days; and the 1-month pooled mortality rate was 0.7%. The authors concluded that referral to an advanced interventional endoscopist for evaluation of polyps in difficult locations with no suspicion of submucosal malignant invasion may be an appropriate strategy to consider before referral for surgery.
Gastroenterology experts are fairly unified in the notion that most polyps, with the exception of Kudo type V and Narrow-Band Imaging International Colorectal Endoscopic classification type 3 lesions, are endoscopically resectable. To that end, the current expert consensus is that referral to an advanced interventional endoscopist should be considered or discussed before referral of any benign precancerous colon lesion for surgical endoscopic treatment. The implications for the endoscopic management of colon polyps are far-reaching, affecting PCPs who assess colonoscopists, gastroenterologists who refer directly to surgery, and surgeons who choose to operate first, without discussion of endoscopic options.
Conclusion
The primary goal of CRC screening is the detection and removal of precancerous lesions in order to prevent cancer. The high-quality performance of colonoscopy, which prevents CRC and death, is the current gold standard for CRC screening. PCPs play a major role in recommending a screening test, preparation agent, and colonoscopy provider. Quality colonoscopy metrics include the use of a split-dose bowel cleansing prepara-
18
16
14
12
10
8
6
4
2
0 5.4
tion and high ADR.
P<0.001
5.9 6.3
EMR + anes EMR + anes + recurrencea
15.5 14.3
Surgery Surgery + complicationsa
Figure 6. Comparison of management costs for resection of large laterally spreading lesions.67
a Estimated. anes, anesthesiology; AUD, Australian dollar; EMR, endoscopic mucosal resection.
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