Almost 18 months after publication of a study on lung cancer screening in the New England Journal of Medicine, the study's lead author, Dr. Claudia Henschke, has disclosed that her study was funded to the tune of $3.6 million by the tobacco industry. The money came from Liggett Tobacco, and was channeled through an innocent-sounding charity - the Foundation for Lung Cancer: Early Detection, Prevention & Treatment - that was set up by Dr. Henschke at Weill Cornell Medical Center.

According to a front-page article by Gardiner Harris in the New York Times, Dr. Henschke is listed as the Foundation's president. David Yankelevitz, MD, one of the study's co-authors, served as the Foundation's treasurer. The Dean of Weill Cornell Medical College, Antonio Gotto, MD, and the vice-chairman of the Weill Cornell board of overseers, Arthur J. Mahon, served on the Foundation's board of directors. This unsavory relationship came to light when the Times examined the Foundation's tax records (Harris, 2008).

Dr. Henschke has been among the most vocal proponents of screening smokers and former smokers in an effort to detect lung cancer in its earliest stages. The unspoken subtext of her argument seems to have been that lung cancer is not such a terrible disease if it can be caught early and cured - a message that would certainly serve the propaganda interests of the tobacco industry.

A Preventable Tragedy

Lung cancer is currently the leading cause of cancer death in the US. Each year more than 215,000 Americans receive a diagnosis of lung cancer, and more than 161,000 die of the disease - exceeding the total number of deaths from breast, colon and prostate cancer combined. The great tragedy is that lung cancer is largely preventable: tobacco smoking is responsible for over 80 percent of all lung cancer deaths.

When detected early (stage 0 and stage I), while the disease is still localized and has not yet begun to spread, lung cancer can very often be successfully treated: the overall 5-year survival rate for patients with localized lung cancer is as high as 50 percent, and a substantial number of patients with early stage lung cancer achieve long term survival. At more advanced stages, however, the disease is almost always fatal: for example, the 5-year survival rate for advanced (stage IV) lung cancer is typically less than 5 percent. Unfortunately, the disease causes no symptoms in its early stages, and early diagnosis is therefore the exception rather than the rule.

A considerable amount of research effort has been expended in trying to find ways to detect the disease before it becomes symptomatic. Screening at-risk populations – primarily current and former smokers - has been advocated by some experts as a promising means of reducing the annual death toll from lung cancer. Prominent among such experts is Claudia I. Henschke, MD, a professor of radiology at Weill Medical College of Cornell University. Dr. Henschke is a staunch advocate of screening for lung cancer using a new chest imaging technique, known as ‘spiral' or ‘helical' CT scanning. Spiral CT scanning is more sensitive than standard chest x-rays and can detect areas of abnormality when they are still too small to be seen by standard radiography.

In late 2006, the prestigious New England Journal of Medicine published the results of the International Early Lung Cancer Action Program (I-ELCAP) study, the principal author of which was Dr. Henschke. The study set out to discover whether screening with spiral CT among susceptible populations (current and former smokers) could have an impact on survival by detecting lung cancer in its most curable stages (Henschke, 2006).

Altogether, 31,567 symptomless (but at-risk) patients were screened at intervals of between 7 and 18 months over the period 1993-2005. A total of 484 patients were given a diagnosis of lung cancer as a result of the screening, of whom 412 were identified as being in stage I. Dr. Henschke and colleagues estimated that the 10-year survival rate of treated patients with stage I lung cancer was 88 percent. They concluded that annual spiral CT screening could detect lung cancer that is curable, and could potentially prevent tens of thousands of lung cancer deaths each year. Dr. Henschke, in a press statement at the time of the paper's publication, said:

"We believe this study provides compelling evidence that CT screening for lung cancer offers new hope for millions of people at risk for this disease, and could dramatically reverse lung cancer death rates."

Naturally, that study garnered tremendous media attention. The possibility that more than 80 percent of lung cancer deaths might ultimately be preventable through screening quickly caught the imagination of the public. Entrepreneurial hospital and private practice managers already advertise whole-body scanning to the public as a means of early cancer detection. Currently, insurers do not cover spiral CT scanning, which can cost anywhere between $400 and $1,000. About half the hospitals in the US own spiral CT equipment, and the prospect of a steady income stream from lung cancer screening is not something any cash flow-conscious hospital management can afford to ignore.

The Downside of Screening

But the medical profession as a whole is by no means as confident as Henschke about the lifesaving potential of mass screening for lung cancer. In a paper published in the Journal of the American Medical Association (JAMA), Peter B. Bach, MD, a leading pulmonologist and epidemiologist at Memorial Sloan-Kettering Cancer Center, strongly disagreed that spiral CT screening could ultimately save most of the lives that are currently lost to lung cancer, and stressed that the hope engendered by the Henschke study was misplaced. Indeed, the Bach study offers convincing evidence suggesting that the adoption of mass CT screening for lung cancer could, on balance, result in more harm than good. "We don't think there is a hint of benefit," said Dr. Bach in an interview with the New York Times (Kolata, 2007)

Previous studies of lung cancer screening using traditional chest x-rays have shown that screening does indeed increase the rate of detection of small (and therefore potentially treatable) lung cancers. However, it has no effect whatever either on the risk of a diagnosis of advanced lung cancer, or on the risk of death from lung cancer (Bach, 2003). The JAMA study by Bach and colleagues showed a similar effect with spiral CT scanning. "When individuals are screened for lung cancer with CT," the authors wrote, "the likelihood that they are diagnosed with lung cancer is increased more than 3-fold, and the likelihood that they undergo a thoracic resection for lung cancer is increased 10-fold. However, as for chest x-ray screening, there appears to be neither a meaningful reduction in the number of advanced cancers being diagnosed, nor a reduction in the number of individuals who die of lung cancer" (Bach 2007).

Spiral CT screening for lung cancer undoubtedly picks up more lung abnormalities. No one disputes this. But what is very much a matter for debate is the question of whether all those abnormalities pose an equally urgent risk to life. Many of the very small cancers that are detected by spiral CT scan might never have progressed to become invasive cancers at all. Yet on the basis of the scan patients are given a diagnosis of lung cancer, and are treated, often with invasive procedures such as surgery and chemotherapy, for a disease that might never have represented any threat to life. Such screening, as Bach and colleagues point out, leads to over-diagnosis: it inflates the statistics on incidence and prevalence, thereby giving an artificial impression of prolonged survival and success in the war against lung cancer.

In addition, a substantial proportion of the lesions picked up by screening ultimately prove not to be cancers at all, but simply scar tissue or harmless nodules. Unfortunately, the only way to determine the nature of any lesion is by biopsy or surgical excision. And such procedures carry significant risks of their own, even in healthy individuals. The risks are commensurately higher in current or former smokers – the very populations most likely to seek screening for lung cancer - whose lung tissue is already less resilient and more susceptible to the harms that accompany intrusive investigations such as biopsy and bronchoscopy.

And then there is the risk of radiation from repeated CT scans. Exposure to radiation during repeated screening poses a significant risk of causing lung cancer in its own right. An intriguing study carried out by David Brenner, PhD, a Columbia University researcher, and published in the journal Radiology, set out to evaluate the radiation risks posed by spiral CT screening for lung cancer in adult smokers. Dr. Brenner's study concluded:

"If 50% of all current and former smokers in the US population aged 50-75 years received annual CT screening, the estimated number of lung cancers associated with radiation from screening would be approximately 36,000 increase over the expected number" (Brenner, 2004).

To be concluded, with references, next week.

CORRECTION: In last week's newsletter we mistakenly referred to Dr. Ronald Hoffman as Dr. Robert Hoffman. Our apologies for this error.

--Ralph W. Moss, Ph.D.