CT Screening: Where Do We Stand?

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Ten years ago, it was nearly impossible to go through the day without seeing an advertisement for whole-body CT screening. Today it’s a different story. The radiation dose exposure from CT scanning has come under intense scrutiny and the value of CT screening must be proved in rigorous trials before many payors, especially Medicare, will consider reimbursing for an exam.

CT scan of 72-year-old woman shows dominant pulmonary nodule (arrow) in right lower lobe that proved at pathology to be adenocarcinoma. Source: American Journal of Roentgenology, Ginsberg et al, 2004.
Image source: American Journal of Roentgenology, Ginsberg et al, 2004

Lung cancer screening

There are primarily two research camps when it comes to lung cancer screening with CT: Those who rely on data from randomized controlled trials (RCTs) to determine whether CT reduces mortality, and those who rely on observational single-arm studies to determine whether CT improves survival.

While this debate rages on, those in the observational camp stand by their data. The International Early Lung Cancer Action Program (I-ELCAP), for example, screened more than 30,000 people, found nearly 500 cancers, of which 85 percent were stage I (N Engl J Med 2006;355:1763-1771). Henschke et al estimated a 10-year survival rate of 88 percent for these patients with stage I cancer caught early. For approximately 300 patients whose stage I cancer was resected within one month of diagnosis, researchers estimated a 10-year survival rate of 92 percent. While patients were followed for 40 months, researchers estimated a mortality reduction of 80 percent at 10 years.

G. Scott Gazelle, MD, PhD, director of the Institute for Technology Assessment at Massachusetts General Hospital in Boston, and colleagues conducted a comprehensive microsimulation model using actual data from a single-arm Mayo Clinic (Rochester, Minn.) lung cancer CT screening study (Radiology 2008;248:278-287). They found a 10-year survival rate of 87 percent, consistent with the 88 percent found in I-ELCAP. However, whereas I-ELCAP estimated a mortality reduction of 80 percent, Gazelle’s model found an 8 percent relative reduction in lifetime lung cancer mortality with five screening exams, and a 14 percent reduction with 10 screening exams. “With single-arm study designs, changes in mortality cannot be quantified,” they concluded.

Proponents of randomized control trials await the outcome from two trials. The National Lung Screening Trial (NLST) is a multi-million, multi-year U.S. study that randomized 53,000 participants to either low-dose CT or chest x-ray. The NLST is designed to detect as little as a 20 percent decrease in mortality. Results should be available this year. The NELSON randomized controlled trial (Netherlands, Belgium and Denmark) randomized approximately 20,000 participants to low-dose CT screening or no screening. The study will have an 80 percent power to detect a mortality reduction of 25 percent. Results should become available within two years.

“It’s not possible to answer all the relevant questions about lung cancer screening with one clinical trial, because of the various patient populations and characteristics,” Gazelle says. Those questions include: Will those screened derive any mortality benefit? If so, how great is it? What is the cost relative to the gains, relative to the costs of other therapies?

Gazelle says the two RCTs mentioned above were powered for a fairly substantial mortality reduction and “even though they are large, expensive and ambitious, they may end up being inconclusive.” Modeling, on the other hand, can tackle large and diverse populations and should be used in conjunction with RCTs, he says.

Currently, no physician-based medical organizations recommend CT lung cancer screening. They cite the conflicting data from previous RCTs and the risks associated with lung biopsy and surgery, as well as a considerable number of false positive lesions that culminate in downstream costs.

Magnified colon polyp via CT colonography is shown in 3D. Typical radiation exposure with CTC is about 3 mSv, the equivalent of the annual natural background radiation to which one is exposed while living in Denver. Source: David J. Vining, MD, University of Texas MD Anderson Cancer Center in Houston
Image source: David J. Vining, MD, University of Texas MD Anderson Cancer Center in Houston

Colon cancer screening

“It’s clear that screening for colon cancer is worthwhile,” says Gazelle, who questions whether CT colonography (CTC) or optical colonoscopy is the superior form of screening. Analyses to date have shown that CTC is not cost effective relative to colonoscopy, he says, adding that CTC is accurate but patients with polyps must then go onto optical colonoscopy.

There are two unknowns with CTC, he says. First, does availability of CTC increase adherence to screening recommendations? Second, what is the effect of extracolonic findings on outcomes? Gazelle and colleagues are developing modeling studies to answer these questions. “It might be that a hybrid strategy is most cost effective. People first get screened with optical colonoscopy, while subsequent screens are with CTC,” he says.

While CMS does not reimburse for CTC screening, some U.S. private payors, including CIGNA, UnitedHealthcare and Anthem BlueCross BlueShield, reimburse, but it is highly variable. A recent bill in the U.S. House of Representatives seeks to mandate Medicare coverage of CTC screening (the Virtual Screening for Colorectal Cancer Act of 2010 [H.R. 5461]). When CMS decided not to pay for CTC screening, however, it cited inconclusive evidence for its benefit relative to colonoscopy, the problem of extracolonic findings and the radiation dose exposure.

Radiation dose is a nonissue, says David J. Vining, MD, a diagnostic radiologist and a professor of radiology at the University of Texas' MD Anderson Cancer Center in Houston. Typical exposure with CTC is about 3 mSv, the equivalent of the natural background radiation that a resident of Denver is exposed to each year.

Extracolonic findings are another matter. Vining says the specialty of radiology needs better practice guidelines on how to handle these. About 10 percent of CT-screened patients will have a significant extracolonic finding, such as lung or kidney cancer. The majority of extracolonic findings, however, are benign entities such as kidney and gall stones or benign tumors.

Vining says that CTC would be the more cost-effective approach compared to optical colonoscopy in a capitated health system. “With a single fee, there is less advantage to scope everybody.” A CTC screening exam costs approximately $300 (if you amortize the cost of the scanner). Reimbursement is approximately $600 and the hospital charges between $750 and $1,000. Optical colonoscopy costs about $700, is reimbursed at about $1,000 and the hospital charges more than $3,000, he says.

He also says that cost-effectiveness analyses by the U.S. Preventive Services Task Force and the Agency for Healthcare Research and Quality failed to include the cost of anesthesia or the cost of anesthesiologists for optical colonoscopy, therefore skewing the results in favor of optical colonoscopy.

Vining is starting a colon cancer screening program this summer at MD Anderson, in which CTC will play a central role. All five major insurers in the area reimburse to some degree for CTC screening. BlueCross BlueShield of Texas manages the University of Texas self-insurance program, and reimburses 100 percent for CTC screening. “There are 18,000 employees at MD Anderson. It will be a huge feat even if we screen one-third of them,” he says. Participants will choose between CTC and optical colonoscopy.

Vining will follow national screening standards set forth by the American Cancer Society (ACS), namely screening those at age 50 and above. A debate surrounding CTC screening, and one argued by gastroenterologists who feel they have turf to lose if CTC becomes commonplace, is that people should go straight to colonoscopy because if polyps are found during CTC, they have to then undergo colonoscopy anyway. But only about 10 to 20 percent of the population has a significant polyp on CTC, Vining says. “The vast majority of very small polyps are hyperplastic. Gastroenterologists tend to remove many polyps that are benign. We have found that it’s not necessary to do so.”

Currently, Vining also is researching better methods for bowel prep, and has built a prototype device that allows patients to adjust the pressure of the gas used to insufflate the bowel to their tolerance level. He also is developing a protocol that will enable same-day bowel prep within 30 to 60 minutes of the exam.

Washington Radiology Associates in Washington, D.C., has been performing CT colonography screening for eight years. Laws in D.C., Virginia and Maryland, where the group practices, mandate that any screening study approved by the ACS must be reimbursed by insurers, says Mark E. Klein, MD, a radiologist with the group. This does not, of course, include Medicare. “CT colonography is highly accurate and very safe,” Klein says. “It’s ridiculous it is not reimbursed by Medicare. The U.S. president recently had one.”

The majority of the group’s patients come from gastroenterologists due to incomplete colonoscopies. The next largest group of referrals is patients on anticoagulants who are contraindicated for optical colonoscopy. The remaining referrals are patients who elect to have screening with CTC rather than optical colonoscopy.

Within his population, less than 10 percent of those screened with CTC have to go on to optical colonoscopy. A fairly normal study takes about 15 minutes to read, whereas more difficult cases can take up to 45 minutes. Most radiologists who perform CTC advocate reading studies in both 2D and 3D.

There is some debate on which technique should be used first. Klein likes to perform an initial overview in 2D, specifically in coronal view. “It’s very quick because big polyps will jump out.” In 3D mode, when he sees a bump, he switches to 2D to “interrogate” the lesion. Vining uses 2D as his primary read, looking first for any extracolonic findings.

Coronary CT angiography study rules out coronary artery disease in a 58-year-old asymptomatic man with multiple cardiovascular risk factors. A dose length product (DLP) of 67 mGycm corresponds to an effective radiation dose equivalent of 0.94 mSv, which is roughly one-third of the annual background radiation from environmental sources. Source: U. Joseph Schoepf, Medical University of South Carolina, Charleston.
Image source: U. Joseph Schoepf, Medical University of South Carolina, Charleston

Coronary artery screening

The era of rampant coronary CT angiography (CCTA) screening has waned since the heydays of the late 1990s and early 2000s. There are facilities that offer “executive” screening programs that generally include coronary artery calcium (CAC) scoring with CT and/or a CCTA, among other tests, but these are generally not covered by insurance. The traditional problem with CCTA has been the high radiation dose exposure, which ranged between 15 and 25 mSv. Today, however, it is possible with the newest technology to have a dose below 3 mSv.

Radiologists at the Medical University of South Carolina (MUSC) in Charleston are expanding their early disease detection primary prevention program to include CCTA in asymptomatic people at extremely high risk for coronary artery disease (CAD). People at high risk are offered either a CAC score alone or a CCTA, which includes a CAC score, says U. Joseph Schoepf, MD, a professor of radiology and medicine and director of cardiovascular imaging at MUSC. The complete exam costs about $1,000.

“With the introduction of our 128-slice dual source scanner [Siemens Healthcare], we started this program because we can now perform a CCTA study with a radiation dose of 1 mSv. In the past, the dose was substantially higher,” Schoepf says.

He is confident they will find people with coronary stenosis greater than 50 and 80 percent. One reason is that diabetics are a target group for screening. “They have silent ischemia without noticing because their pain receptors are impaired by diabetes.” He says, however, that the more interesting and relevant question regarding CCTA screening is what action to take based on these findings. The quality and success of a screening test depends on the availability of better alternatives, alternatives that change the patient’s course from worse to better.

Opponents of CAC or CCTA screening say that screened patients won’t receive different management than unscreened patients at risk for CAD. “That is in essence true,” Schoepf says. “Certainly, in an ideal world governed by guidelines, people with risk factors should be managed and treated as high risk, but this doesn’t always happen. Screening has an impact by making sure that the appropriate management strategies and guidelines are applied.”

A 2009 study by economist Frank R. Lichtenberg for the National Bureau of Economic Research found a correlation between the increased use of advanced imaging techniques (CT and MRI), as well as newer drugs and better quality physician education, and decreased mortality. Interestingly, the states with larger increases in advanced imaging procedures did not have larger increases in per capita medical expenditure. The report noted that this finding is inconsistent with studies that found “advances in medical technology have contributed to rising overall U.S. healthcare spending.”

There is a renewed interest in the benefit of CAC screening. The exam is inexpensive, costing about $200, and uses a low dose. Last year, Texas required insurance companies to pay for either a CAC screen or a carotid intima-media thickness ultrasound screen.

Polonsky et al found that a CAC score added to traditional risk factors improved event risk prediction (JAMA 2010;303(16):1610-1616). They did not, however, determine whether or not clinical outcomes also would improve.

Shaw et al found that CAC screening resulted in low annual downstream costs, approximately $35 for those with a CAC score of less than 100 (J Am Coll Cardiol 2009; 54:1258-1267). These patients constituted 78 percent of their screened population. Conversely, costs rose as the CAC score increased, but this did not lead to a disproportionate rise in invasive catheter angiography. “This result is consistent with a recent report noting that the addition of one CT scanner for cardiac applications resulted in a reduction in 15.4 [per 100 scanners] fewer invasive coronary angiographies,” the authors concluded.

Recent studies also have shown that adding a CAC score to SPECT or PET perfusion exams is beneficial. Chang et al found that asymptomatic patients with normal SPECT results but a CAC score greater than 400 have nearly a four-fold increased risk of cardiac events and death (J Am Coll Cardiol 2009;54;1872-1882). “Our most provocative finding was that although a normal SPECT result predicts excellent short-term event-free survival, long-term outcome is significantly worse if the CAC score is severe,” says senior author John J. Mahmarian, MD, a cardiologist at the Methodist DeBakey Heart and Vascular Center in Houston.

And finally, Bybee et al found that a significant percentage of patients with a normal PET/CT perfusion test had a CAC score greater than 100 (J Nucl Cardiol 2010;189:88-96). They also found that a significant proportion of patients with intermediate and high Framingham Risk Scores (FRS) had little or no coronary calcification, while 57 percent of patients in the low FRS group had evidence of subclinical CAD.

Alan Kaye, MD, radiology chair at Bridgeport Hospital in Bridgeport, Conn., offers lung and CAC screening. He doesn’t push the lung cancer screening because of data published in the mid-2000s suggesting a potential lead-time bias. The data for CAC screening, however, are very robust but there is a “general malaise with respect to new imaging tests, both within and outside the radiology community, which has me concerned.”

He suggests that the bar has been set higher for newer imaging tests, which must be proven to improve patient outcomes in terms of saving lives and be shown to be cost effective. Also, the criteria and stringency with which the evidence is looked at is not uniformly applied. “We know the Framingham Risk Score is a good predictive value and helps guide therapy. We also know that CAC scoring enhances the predictive value of Framingham or supplements it; so, one would assume the CAC test is better for patients. But we can’t take that leap.”

Overall, the radiology community will know within a year the results of the NLST and whether CT screening for lung cancer is efficacious. The heat has been turned up regarding CTC screening as Congress seeks to have CMS reimburse for the test. And if the Houston-based Society for Heart Attack Prevention and Eradication, which supported the bill requiring Texas insurers to pay for CAC screening, can move beyond the Texas borders, we might see a groundswell of support for this relatively inexpensive but proven test to help curb spending on cardiovascular disease. Stay tuned.