Computed tomographic screening for lung cancer: Home run or foul ball?

TY - JOUR

T1 - Computed tomographic screening for lung cancer

T2 - Home run or foul ball?

AU - Swensen, Stephen J.

AU - Jett, James R.

AU - Midthun, David E.

AU - Hartman, Thomas E.

N1 - Funding Information: Stephen J. Swensen MD a * James R. Jett MD b David E. Midthun MD b Thomas E. Hartman MD a a Department of Radiology, Mayo Clinic, Rochester, Minn b Division of Pulmonary and Critical Care Medicine and Internal Medicine, Mayo Clinic, Rochester, Minn * Individual reprints of this article are not available. Address correspondence to Stephen J. Swensen, MD, Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 In the past 4 years of studying computed tomographic (CT) screening for lung cancer, we have identified 56 lung cancers (29 prevalence [identified on baseline scan], 23 incidence [identified on subsequent annual screening], and 4 interval [diagnosed between annual screenings]). Of the non–small cell lung cancers, 62% were stage IA—great news. 1 In practice today, only 15% to 20% of lung cancers are stage IA at presentation. In patients with stage I lung cancers, 5-year survival is 60% to 70%. There is absolutely no question that CT is more sensitive for small lung cancers at earlier stages than is chest radiography—we have found four 3-mm cancers. Why would you ever want to wait until these 56 patients with lung cancer had symptoms and later-stage disease? This is an amazing opportunity to save hundreds of thousands of lives in a few years. Sounds like a game-winning home run for technology against the deadliest cancer team on the planet. But is it a home run, or will the ball sail outside of the foul pole? Do not cool the champagne just yet. The visiting lung cancer team is ruthless, aggressive, and tenacious (they lose only 13% of the time). Their pitcher has some formidable curve balls, sliders, and change-ups: • Are most lung cancers simply too fast? Is biology destiny? Is the value of earlier detection (which CT clearly provides) moot? Angiogenesis occurs at 1 to 2 mm for many tumors. 2–4 When does metastasis occur? • Are other lung cancers too slow? Is overdiagnosis (pseudodisease) a confounding antagonist? We are surely finding more early-stage lung cancer. But will there be the same number of advanced-stage tumors? If we find the same rate of cancer in screened smokers as in those who never smoked, are we fooling ourselves, gloating over “die-with” cancers? 5 • Are there simply too many lung nodules to have acceptable quality of life for screened patients? In our series, more than 70% of participants had 1 or more uncalcified lung nodules, and 98% of uncalcified lung nodules detected were benign (a false-positive finding for lung cancer). There are more than 90 million current and past smokers in the United States. If you were to extrapolate our findings to just this population, you would expect to find more than 180 million lung nodules. Is that too many? • Will the false-positive examinations make screening too expensive? Does $116,300 to $2.3 million per quality-adjusted life year make sense? 6 • What about too risky? Is the mortality associated with surgery for lung cancers and benign nodules too great a hurdle to overcome for screening to lower disease-specific mortality? Multicenter studies in both the United States and Europe show that about 50% of lung nodules removed at surgery are benign. 7,8 The risk: 3.8% mortality with wedge resections of lung nodules in community hospitals in the United States. 9 First, do no more harm. • Is there too much radiation in follow-up examinations? Could radiation exposure induce more cancer deaths than it prevents? • Are the high-risk people who are most likely to benefit from screening too sick? Are their comorbidities and competing risks from smoking too high? Even if earlier detection of lung cancer would otherwise save their lives, do they end up dying of stroke, heart disease, or obstructive lung disease? Are there fundamentally too many too's, or are we just acting too soon? (Do we need to wait for the right biomarker and send only the right people to bat?) The whole-body CT screening game is being played on the baseball diamond just across the street. It has the same rules but no umpires. It also has enticing testimonials that play great on billboards and radio sound bites: “In our cohort we found 4 renal cell carcinomas, 3 breast cancers, 2 lymphomas, 2 gastric tumors, 1 pheochromocytoma, and 114 abdominal aortic aneurysms.” 1 However, most “clinically significant” ancillary findings were falsely positive, resulting in measurable collateral damage similar to that of lung cancer screening. Yet many spectators are choosing to take a turn at bat. What do the fans think of all this? Of course they are rooting for the home team, but many are weary from decades of losing and dubious of victory. These fans memorize batting averages (instead of just enjoying the game) and congregate with professional medical societies and insurance companies. Many others (high-risk patients, entrepreneurs, and optimists) believe that the home team has already won and that the umpire should just call the game. Fans from all over the world are watching closely. The ball has been solidly struck. Some see a game-winning home run; others see just another foul ball in this serious game. Both teams have ethicists batting cleanup, who have genuine differences of opinion—equipoise. Enter the umpire. The “umpire,” the National Lung Screening Trial (NLST), funded by the National Cancer Institute, is now under way. It is the best umpire in town (50,000 participants randomized to screening chest CT or radiography with a mortality end point) but works slowly—it could take 5 to 10 years to call the game. • Eligibility: current or former heavy smokers aged 55 to 74 years with no history of cancer in the past 5 years • To learn more or to enroll: 1-507-266-1190 or 1-888-885-7503 In the meantime, we must be patient and stay in the bleachers, working to make sure the NLST is successful. You may suggest to your patients that they enroll in the NLST (or in another study if NLST is not an option). What if your patients simply want to get scanned? Take the time to discuss the pros and cons. If you have no financial conflict of interest, you are in the best position to give balanced informed consent. As their fiduciary, you should tell your patients in no uncertain terms that there is no proven benefit and that there are serious risks involved that could even outweigh benefits (if indeed there are any). The stakes in this game are extremely high. The umpire is wearing an evidence-based medicine uniform and the left- field bleacher fans are climbing over seats to catch what they hope is a home run ball. … Stay tuned. There is a long fly ball deep to left field. It will clear the fence, but is it fair or foul?

PY - 2003/9/1

Y1 - 2003/9/1

UR - http://www.scopus.com/inward/record.url?scp=0042859843&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042859843&partnerID=8YFLogxK

U2 - 10.4065/78.9.1187

DO - 10.4065/78.9.1187

M3 - Comment/debate

C2 - 12962174

AN - SCOPUS:0042859843

VL - 78

SP - 1187

EP - 1188

JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

SN - 0025-6196

IS - 9

ER -