Current Controversies in Oncology

Introduction

Al B. Benson III , MD
Robert H. Lurie Comprehensive Cancer Center
Northwestern University

Colorectal cancer is a leading cause of cancer death that is also a potentially preventable disease by applying screening strategies. The subject of colorectal cancer screening has been one of significant interest with extensive efforts undertaken to improve not only the rate of screening, but also to explore alternative methods of screening.

Recent literature has emerged evaluating the optimal role of two important technologies, optical colonoscopy and computed tomographic (CT) colonography. Although the Centers for Medicare & Medicaid Services (CMS ) will reimburse optical colonoscopy for the purposes of colorectal cancer screening, CMS denied reimbursement for CT colonography in its February 2009 Proposed Decision Memorandum.¹ CMS stated that the evidence was inadequate to justify the use of this screening modality, expressing concerns that it is not yet possible to generalize study results to support its use in an older population of patients. In addition, the U.S. Preventative Services Task Force has not endorsed CT colonography screening. The CMS decision has raised significant concerns prompting the mailing of letters to the CMS Acting Administrator from Members of Congress, including the Congressional Black Caucus.

The following represents two independent points of view: the merits of CT colonography, presented by Abraham H. Dachman, MD, versus those of optical colonoscopy, presented by Hemant K. Roy, MD, and Michael J. Goldberg, MD. Important areas of discussion include the availability of gastroenterologists to perform colonoscopy screening, cost, patient acceptance, bowel preparation, radiation exposure with CT colonography, detection of small polyps and flat lesions, safety, avoidance of unnecessary biopsies, and colonoscopy as a “one-step” procedure for localization and biopsy examples.

Reference

1. Centers for Medicare & Medicaid Services. Decision memo for screening computed tomography colonography (CTC) for colorectal cancer (CAG -00396N). https://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=220. Accessed 17 July 2009.

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"Current Controversies in Oncology" is a forum for the exchange of views on topical issues in the field of oncology. The views and opinions expressed therein are those of the authors alone. They do not necessarily reflect the views or positions of the Editor or of the American Society of Clinical Oncology.

CT Colonography Should Be Offered as a Screening Test

Abraham H. Dachman, MD
Department of Radiology
University of Chicago Medical Center

There is a critical and immediate need to improve screening for colorectal cancer (CRC)¹ and the best option today is acceptance of computed tomographic (CT) colonography (CTC) in addition to optical colonoscopy (OC).² These alternatives provide synergistic alternatives for a diverse population at risk for CRC, and together provide benefits that exceed the sum of their respective contributions.

The benefits accrue in cost, acceptance, utilization, and ultimately in overall survival. There is evidence that the full approval of optical colonoscopy by Medicare in 2002 played a major role in improved compliance with American Cancer Society (ACS) screening guidelines.³ The approval of barium enema as a CRC screening test was important, but its use, while still representing a significant component of Medicare reimbursement costs, continues to decline. The 43% sensitivity for 10 mm polyps by barium enema^4,5 was not the problem. I believe the public did not perceive barium enema as a desirable test. On the other hand, CTC has developed since its introduction in 1993 to become a test known to the public. Although only a few centers of excellence perform high-volume screening CTC, increasing numbers of radiologists have introduced CTC into their practice.

The proliferation of CTC screening exams into general radiology practice was initially hampered by lack of endorsement by the medical community and a lack of widespread reimbursement. This has gradually changed; with the publication of the American College of Radiology Imaging Network (ACRIN ) National Colonography Trial,⁶ CTC was endorsed by the ACS, the Blue Cross/Blue Shield Technology Assessment,⁷ and the U.S. Multi-Society Task Force on CRC.² CT scanner and CTC interpretation software continue to improve and the capacity to perform CTC nationally has been realized. The ACR developed standards,⁸ intensive hands-on educational courses that can accommodate a large number of radiologists documented by a certificate of participation for the interpretation of at least 50 carefully selected teaching cases. Other educational opportunities have been developed by the pharmaceutical industry, by universities, and through online resources, all of which will facilitate the training of radiologists on a national scale. As of April 2008, at least partial reimbursement for CTC existed in 43 states (often including Medicare reimbursement for incomplete OC done for a diagnostic indication).

Several recent studies have addressed the cost effectiveness of CTC with favorable results. Pickhardt et al. used a Markov model and showed CTC to be cost effective when used as recommended (ignoring diminutive polyps smaller than 5 mm).⁹ CTC advocates do not suggest that CTC should replace OC, but the comparison to OC should be fair and include the false negative rate, cost of unnecessary biopsies, and complications. In a recent comparison of more than 3,100 patients in each arm of a screening program in which patients chose between CTC or OC screening, the detection and removal of advanced neoplasia was comparable, yet CTC resulted in only 561 polypectomies (and no CTC complications) versus OC which had 2,434 polypectomies and seven colonic perforations.⁹ The referral rate to OC from the CTC screening arm was 7.9%, consistent with a very costeffective program. The issue of polyp size threshold and CTC sensitivity for diminutive lesions has also been addressed.¹⁰

The cost of additional workup incurred as a result of potentially significant extracolonic findings (not including surgical expenses) has been estimated to be between a mean of $24 and $34 per patient, and 0.2%-2% of asymptomatic patients may be referred for surgery.¹¹ Regarding radiation, the radiation doses are less than those of a barium enema and often less than the yearly ambient population exposure to radiation.

Compliance would improve further if CTC was fully reimbursed by Medicare and private carriers. I am concerned that the failure of the Centers for Medicare & Medicaid Services (CMS ) to endorse CTC created a new misconception, by the public and by primary care physicians, that CTC is rarely reimbursed. In our practice, the percent of self-pay CTC patients has dropped from 60% to 10% even though our volume is steady.

Yes, I am a CTC enthusiast and I think CTC is ready for prime time. My perspective is strongly endorsed by respected and objective non-radiologists. In particular, I quote from one documented eloquent rebuttal of the CMS decision,¹² that states, “If the criteria applied by CMS to CTC were re-applied universally to all therapies, it is likely that no drug on the market today would pass the test.”

References

1. Umar A, Greenwald P. Cancer Epidemiol Biomarkers Prev. 2009;18:1672-73.
2. Levin B, Lieberman DA, McFarland B, et al. CA Cancer J Clin. 2008;58:130-60.
3. Gross CP, Andersen MS , Krumholz HM , et al. JAMA. 2006;296:2815-22.
4. Winawer SJ, Stewart ET , Zauber AG , et al. N Engl J Med. 2000;342:1766-72.
5. Rockey DC, Paulson, E, Davis W, et al. Lancet. 2005;365:305-11.
6. Johnson CD, Chen MH , Toledano AY , et al. N Engl J Med. 2008;359:1207-17.
7. Blue Cross Blue Shield Technical Evaluation Center. Technology evaluation center assessments. www.bcbs.com/blueresources/ tec/press/ct-colonography-virtual.html. Accessed July 17, 2009.
8. American College of Radiology. ACR practice guideline for the performance of computed tomography (CT) colonography in adults. ACR Practice Guideline. 2005;Res.29:295-98.
9. Pickhardt PJ, Hassan C, Laghi A, et al. Cancer. 2007;109:2213-21.
10. Kim DH, Pickhardt PJ, Taylor AJ, et al. N Engl J Med. 2007;357:1403-12.
11. Pickhardt PJ, Hanson ME , Vanness DJ, et al. Radiology. 2008;249:151-59.
12. Pickhardt PJ, Kim DH. AJR Am J Roentgenol. 2009;193:40-6. 13. Lichtenfeld L. American Cancer Society. http:// www.cancer.org/aspx/blog/Comments. aspx?id=307. Accessed June 25, 2009.

An Argument for Optical Colonoscopy

Hemant K. Roy, MD
Michael J. Goldberg, MD
NorthShore University HealthSystems
Department of Internal Medicine
University of Chicago
Pritzker School of Medicine

The major focus for colorectal cancer (CRC) screening has evolved from early diagnosis to cancer prevention through the identification and removal of adenomas.¹ Colonoscopic screening has been documented to reduce risk for future CRC by 75%-90% and thus has become the “gold standard.”² The multi-society guidelines also recommended flexible sigmoidoscopy and CT colonography (CTC) for adenoma detection.¹ Since flexible sigmoidoscopy is limited by its inability to assess the proximal two-thirds of the colon, interest has turned to CTC as a less intrusive option for pan-colonic evaluation. However, as detailed below, there are significant challenges in implementing CTC for CRC population screening.

The first issue for CTC is the ability to detect adenomas and hence interrupt the adenoma-carcinoma progression. There are many widely divergent estimates of performance characteristics. For instance, in an observational single-center trial, the detection rate for adenomas =10 mm was comparable to colonoscopy, although this non-randomized study was limited by potential selection bias and lack of colonoscopic confirmation of most CTC findings.³ On the other hand, previous randomized multicenter trials have reported that CTC had poor sensitivity for adenomas =10 mm (55%-59%), but has been criticized for using earlier generation technologies.^4,5 Fortunately, there have been two recently published, rigorously conducted multicenter randomized trials. These studies have yielded remarkably similar sensitivities for clinically significant adenomas (>9-10 mm) in average and higher-risk cohorts (84% and 80%, respectively). ^6,7 For non-diminutive (=5 mm) adenomas, the performance was even poorer (65% and 72%).^6,7 Even for CRCs, CTC miss rate was not trivial (approximately 6%).^6,7

Share Your Thoughts and Opinions in a Letter to the Editor Provide feedback about Current Controversies in Oncology. Letters should be less than 250 words and may be edited for length, clarity, and accuracy. All correspondence should include a daytime telephone number, current mailing address, and e-mail address. ASCO News & Forum cannot acknowledge or return letters. Letters become the property of ASCO and may be published in all media. To submit a letter, send an e-mail to asconews@asco.org; write to Letters to the Editor, ASCO News & Forum, ASCO, 2318 Mill Road., Suite 800, Alexandria, VA 22314; or send a fax to 571-366-9550.

Management of CTC-identified neoplasia represents one of the most vexing clinical challenges. Typically, during colonoscopy all visualized lesions are removed, reasoning that large polyps/ CRCs evolve from smaller lesions. For CTC, referring every patient for polypectomy is impractical from both a cost and patient satisfaction perspective (i.e., logistic constraints would probably necessitate a second visit and bowel prep). Therefore, the crux of these performance issues centers on the consequences of lesions either missed by CTC or identified but left in situ. Most authorities consider it reasonable to ignore adenomas <5 mm.⁸ Although one could argue that polyps of 6-9 mm have a low risk of harboring advanced features, this is not negligible (6.6%)⁹ and may be higher in the subset (approximately 10%) of lesions classified as flat and depressed.¹⁰ Indeed, electing to leave a potentially premalignant lesion in place is unacceptable for most patients and may have medico-legal ramifications.¹¹ Even if one confined colonoscopy to only patients with =10 mm lesions, given the positive predictive value of CTC is only 0.23, approximately one-fifth of the average-risk population would require the second test.⁶

An important consideration is patient acceptability, as compliance is a major obstacle in population screening. From a patient perspective, CTC is less intrusive than colonoscopy but still requires a bowel purge (the major reason for patient non-compliance)¹² and a rectal catheter for air insufflation which is performed without benefit of sedation. In fact, studies on CTC and colonoscopy have failed to yield dramatic differences in patient preferences.¹³ With regard to risks, colonoscopic complications are rare but not insignificant (perforation, bleeding, sedation). CTC appears safer although concern has been raised regarding neoplasia occurring secondary to radiation exposure from serial examinations.¹⁴

Another area that must be addressed is the extra-intestinal lesions observed on CTC. Superficially, this may appear to be a “bonus.” However, these are extraordinarily common, seen in two-thirds of cases with 16% deemed to require further investigations.⁶ Although some findings may benefit the patient (aortic aneurysms, etc), the majority are simply “incidentalomas” that still obligate followup testing that results in unnecessary expense, patient anxiety, and potential complications.^15-17

In conclusion, CTC represents an important technological advance but in order to make a significant contribution to the average-risk screening armamentarium, there are several critical issues that still need to be resolved. Thus, at this juncture, we believe that CTC’s numerous important limitations, especially the lack of therapeutic ability, preclude its designation as a preferred CRC screening strategy. We, therefore, concur with the decisions not to endorse CTC by the U.S. Preventive Services Task Force (being particularly concerned about the potential harms associated with “incidentalomas”)¹⁸ and the Centers for Medicare & Medicaid Services.¹⁹ As the technology and clinical paradigms mature, CTC may have a role in screening a subgroup of patients, including those with multiple comorbidities, those refusing colonoscopy, and possibly patients at lowest risk of CRC.²⁰ However, at present, we believe that the evidence strongly supports colonoscopy as the dominant CRC screening strategy.

References

1. Levin B, Lieberman DA, McFarland B, et al. Gastroenterology. 2008;134:1570-95.
2. Winawer SJ, Zauber AG , Ho MN , et al. N Engl J Med. 2007;357:1403-12.
3. Kim DH, Pickhardt PJ, Taylor AJ, et al. N Engl J Med. 2007;357:313-5.
4. Cotton PB , Durkalski VL , Pineau BC, et al. JAMA. 2004;291:1713-9.
5. Rockey DC, Paulson E, Niedzwiecki D, et al. Lancet. 2005:365:305-11.
6. Johnson CD, Chen MH , Toledano AY , et al. N Engl J Med. 2008:359:1207-17.
7. Regge D, Laudi C, Galatola G, et al. JAMA. 2009;301:2453-61.
8. Butterly LF, Chase MP , Pohl H, et al. Clin Gastroenterol Hepatol. 2006;4:343-8.
9. Lieberman D, Moravec M, Holub J, et al. Gastroenterology. 2008;135:1100-5.
10. Soetikno RM , Kaltenbach T, Rouse RV, et al. JAMA, 2008;299:1027-35.
11. Shah JP, Hynan LS , and Rockey DC. Am J Med. 2009;122:687,e1-9.
12. Beebe TJ, Johnson CD, Stoner SM , et al. Mayo Clin Proc. 2007;82:666-71.
13. Rockey DC. Gastroenterology. 2009;137:7-14.
14. Brenner DJ and Hall EJ. N Engl J Med. 2007;357:2277-84.
15. Fletcher RH , Pignone M. Arch Intern Med. 2008;168:685-6.
16. Kimberly JR, Phillips KC, Santago P, et al. J Gen Intern Med. 2009;24:69-73.
17. Whitlock EP , Lin JS, Liles E, et al. Ann Intern Med. 2008;149:638-58.
18. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:627-37.
19. Mitka M. JAMA. 2009;301:1327-8.
20. Lin OS , Kozarek RA , Schembre DB, et al. Gastroenterology. 2006;131:1011-9.