An honest take on screening for lung cancer

This could be an early sign of more honesty where it concerns new screening tests. In the not-so-distant past, screening tests were introduced to physicians and the general public with great enthusiasm but virtually no acknowledgement of harm. Too often that information came 20 to 40 years later (think PSA and mammography), if at all. Now low-dose lung scans have just received the official blessing as a screening test from four major professional organizations, including the American Cancer Society. Here’s what stands out—not only are the known harms acknowledged but so are the uncertainties.

The stamp of approval comes after an in-depth review of all relevant studies that appeared recently in the Journal of the American Medical Association. Here is the conclusion: “Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.”

Let me translate this less-than-ringing endorsement. The rate of lung cancer deaths avoided by this expensive high-tech procedure is extremely low, despite the fact that it was confined to heavy smokers and former heavy smokers who quit in the last 15 years.  More on deaths-avoided later.

As for the “generalizability of results” this refers to an underappreciated point that applies to most findings from clinical trials. The care delivered in a clinical trial is usually far better than that delivered in the real-world practice of medicine. Yet the single large clinical trial that formed the basis for the new review is an unusual mix of both. The diagnostic workups and treatments of the trial took place in the real world (academic medical centers, community hospitals, or doctor-owned radiology clinics). But all the images were interpreted by radiologists, who had extra training in the interpretation of low-dose CT scans and more experience with this particular technology than the average radiologist.

This government-funded study, called the National Lung Screening Trial, was described in the review as “the most informative.” It is the largest study (52,000 participants) and the only one that randomly assigned high-risk people to undergo either a CT scan or another already-discredited screening test (chest x-ray). All participants had one screening procedure annually for three years and then were followed for three more years.

Attempts were made to assess the harms. For example, the reviewers estimate that one cancer death would be caused by the radiation exposure of three scans “for every 2,500 persons screened, although this death would likely occur many years later.”  Short-term  estimates of false-alarms and unnecessary lung biopsies were mentioned.  Amazingly, so was overdiagnosis (defined as “histologically confirmed lung cancers identified through screening that would not affect the patient’s lifetime if left untreated. This includes patients who are destined to die of another cause.”) Unfortunately, the reviewers say, “The rate of overdiagnosis [and the inevitable overtreatment] cannot yet be estimated.”  Such gaps in information explain why “uncertainties about potential harms” appears in the review’s conclusion.

Lung scanning was introduced over 20 years ago as a diagnostic test, but there is no reliable information about how long or how frequently it has been used as a screening test. The latter use is a money-maker for hospitals, especially those advertising their high-tech equipment directly to the public. It is unlikely that the first wave of screening customers was giving their informed consent since there was no information to provide until 2010. This is the year when the National Lung Screening Trial posted its preliminary results on the National Cancer Institute’s website.

The final results of this trial are central to the newly published review, and here is how its authors describe lung scanning’s lifesaving advantage over chest x-rays: “The chance of dying from lung cancer was 0.33% less over a three-year period.”

Put another way: 99.6% of high-risk smokers and former smokers will risk the adverse effects of this test but gain no lifesaving benefit. Put yet-another way, one lung cancer death avoided out of every 320 people screened.

This review is described as “a collaborative initiative of the American Cancer Society, the American College of Chest Physicians, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network.   Disclosure: I served as consumer representative on one of the committees within this collaborative. It struck me as downright stupid that we were not permitted to look at the most obvious consideration: Is this expensive technology cost-effective?   Unlike countries with high-quality medical care systems, the U.S. has a toxic politial climate that does not allow this question to be explored. The word rationing would be hurled at any conclusion that indicates the answer is no.

Maryann Napoli, Center for Medical Consumers©
Related posts:
Screening scans for smokers and former smokers 2011 post describes heavy smokers and the National Lung Screening Trial in greater detail.
Are you a smoker or former smoker? 2010 post describes an earlier lung scanning trial and why its results are unreliable.

Lung screening scans for smokers

At the end of last year, the National Cancer Institute announced that it had stopped its lung screening trial earlier than planned. The reason: fewer lung cancer deaths among participants screened with CT lung scans compared with those screened with chest x-rays. This landmark trial is the first to show that screening can reduce lung cancer mortality in people with a history of heavy smoking. Because the National Lung Screening Trial (NLST) is taxpayer-funded, its results were reported directly to the public on the NCI website. But the NCI also made it clear that the harms associated with lung screening would not be known for months. The missing information came in this week’s issue of the New England Journal of Medicine.

The harm of screening lung scans is primarily, but not limited to, false alarms. That is, of course, the risk of all screening tests. Mammography, for example, has a high rate of false-alarms (false-positives), and studies show that most women accept this as the “price to pay” for what they perceive as the lifesaving benefit for mammography. But unlike a biopsy of the breast, which is, after all, an appendage, a needle biopsy of the lung is much riskier. Complications include death (rare, we are told) and collapsed lung (common for smokers and former smokers). Some NSLT participants went on to more invasive, risky procedures like thoracotomy and mediastinoscopy for abnormalities that turned out not to be cancer.

If you are a smoker or former smoker, your decision to be screened with a CT lung scan should involve weighing the benefit against the harms. The first thing to consider is whether you fit the profile of the people who participated in the NLST. They were male and female smokers and former smokers, age 55 to 74 years*, who were symptom-free at the start of the trial. All had smoked one pack a day for 30 years, or two packs a day for 15 years, or three packs a day for at least 10 years in the previous 15 years. The more than 53,000 participants were randomly assigned to have either a low-dose spiral computer tomography (CT) lung scan or a standard chest x-ray annually. The trial was stopped at 3 years and continued to followed participants for 3 ½ more years.

There were 356 lung cancer deaths among the more than 26,000 participants assigned to receive a spiral CT lung scan, compared to 443 among the 26,000 participants given chest x-rays (either way, a surprisingly low number of deaths for such high-risk people followed over a six-year period). But this benefit came at a huge cost in terms of money, health, and worry to the one in four people, whose scans indicated cancer, leading to more tests, a needle biopsy, and in some cases, an invasive procedure before a false-alarm was ultimately determined in the overwhelming majority of cases. False-alarms occurred in both groups, but scanning found far more abnormalities that looked like cancer before they were ultimately judged to be benign. The scans cost a couple of hundred dollars each; the “cascade” of tests that can follow are costly.

Though “low-dose” is part of its description, CT scans involve a radiation dose far higher than a standard chest x-ray but less than the standard CT scan click here. Whether annual spiral CT lung scanning itself causes lung cancer is yet to be determined. For screening mammography, the NCI estimate is: There are between 10 and 32 radiation-induced breast cancers for every 10,000 women exposed to accumulated doses of radiation received over the years from multiple mammographic examinations.

Although hospitals have already started targeting smokers with advertising for annual screening lung scans, the authors of the NLST, led by Christine Berg, MD, of the NCI’s Early Detection Research Group, do not think the technology is ready for prime time both for cost-effectiveness and safety reasons.  One concern—and it applies to all research projects—is the care delivered in the context of a clinical trial is likely to be far better than that received in the everyday practice of medicine. In the editorial that accompanied this study, Harold C. Sox, MD, Dartmouth Medical School, points out that the NLST took place at 33 academic medical centers, but the diagnostic testing and cancer treatment took place in the community, aka the real world. Dr. Sox is encouraged by the fact that the rate of death associated with diagnostic procedures was low because it indicates that diagnostic care in the community is good. However, where it concerns the radiologists who read the scans for the NLST participants, Dr. Sox suggests their skills were probably far higher than their counterparts practicing in the community. The NLST radiologists “had extensive training in the interpretation of low-dose CT scans and presumably a heavy low-dose CT workload.”

Dr. Sox wrote that he agreed with the authors of this study. “…policy makers should wait for more information before endorsing lung-cancer screening programs.”

*Participants in their seventies were underrepresented in this study (fewer than 3% of all). This means that less is known about the safety and effectiveness of screening people over age 70.

See this August 7, 2011 lung screening addition to TheNNT.com website. 

Maryann Napoli, Center for Medical Consumers©