By Erin Sherbert
By Erin Sherbert
By Leif Haven
By Erin Sherbert
By Chris Roberts
By Kate Conger
By Brian Rinker
By Rachel Swan
"And all of a sudden, we can now take the most common cause of [cancer] death in both men and women and do something about it. I mean, that's what I went into medicine to do, to make a difference, and now we can."
The idea of screening for lung cancer dates to the 1940s, when physicians first noticed the increasing number of men whose smoking habits resulted in premature death. By the late 1960s, after the surgeon general had declared that cigarettes do indeed cause cancer, several clinical trials had been constructed in attempts to determine whether screening tests could find lung cancer in its early stages, when surgery, radiation, and other treatments might improve survival rates. The largest such trial, the Mayo Lung Project, also became the most controversial.
As the Mayo Clinic's chief resident in the early 1970s, Fred Grannis operated on many of the patients involved in the landmark study, a randomized, controlled trial of screening with chest X-rays. Funded by the National Cancer Institute, the study was conducted between 1971 and 1983, and enrolled nearly 10,000 male smokers over the age of 45. Half received free chest X-rays and sputum tests every four months for six years; the other half received the Mayo Clinic's standard 1970 recommendation to receive the same tests, but just once a year.
"I've always thought that trial was positive, that it proved lung cancer was picked up at an earlier stage by using chest X-ray screening," Grannis says. "But the epidemiologists use the gold standard of population mortality, and there was no difference in population mortality. So they won."
Indeed, the conclusions of that study, released in 1986, have effectively prevented mass screening from becoming a reality in the United States. Although nearly everyone who has ever discussed the Mayo Lung Project admits the study was flawed -- about half of the patients in the control arm received intermittent chest X-rays, contaminating the data -- the trial found that screening with chest X-rays at frequent intervals does not decrease the death rate from lung cancer.
Ten years later, researchers at the National Cancer Institute completed a follow-up on the Mayo Lung Project and reinforced its original conclusions. At the end of 1996, after more than 20 years of tracking the study's subjects, the number of deaths from lung cancer was statistically identical for those in the screening and "usual care" arms, despite longer survival times, measured from diagnosis to death, for men who were screened. The follow-up study's lead author, Dr. Pamela Marcus, an epidemiologist in the NCI's Division of Cancer Prevention, argued that the greater survival time was simply a result of the chest X-rays picking up tumors that did not become lethal.
Seeking to provide a more definitive answer to the question of whether chest X-rays save lives, the NCI launched another large-scale study in the early 1990s, the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial. Unlike the Mayo Lung Project, the PLCO trial includes women, and has enrolled nearly 150,000 participants. The results, however, are not due until at least 2015, and, because of advances in technology, they may well be meaningless by that time.
Even as the scientific dispute over the usefulness of X-rays continued, interest in CT scanning as a way to detect lung cancer exploded.
In 1999, Claudia Henschke, chief of chest imaging at New York Weill Cornell Medical Center and a principal investigator for the International Early Lung Cancer Action Project (ELCAP), a global association of doctors and medical centers that includes Grannis and City of Hope, shook the medical community with the results of a prospective trial of CT scans. Her study, published in the British medical journal Lancet, was not of the fully randomized and controlled type often preferred for new medical tests and therapies. All 1,000 participants in this ELCAP study received CT scans. But the results showed that CT scans are far more effective at detecting early-stage cancers than X-rays, with CT scans revealing more than 80 percent of lesions in Stage I. Now, only about 7 percent of lung cancers are found this early, when they might be cured by surgery alone, and most aren't detected until a patient exhibits symptoms -- usually no sooner than Stage III, when the likelihood of surviving five years is just 10 to 15 percent .
CT scan advocates say this improved ability to find early-stage lung cancer is a historic advance that will allow faster treatment and an improved medical outlook for millions of smokers and ex-smokers. In the ELCAP study, 96 percent of the small lesions detected by the CT scans were able to be surgically removed, with a typical five-year survival rate of 67 percent.
"Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer, at an earlier and potentially more curable stage," Henschke wrote. What's more, she suggested a protocol -- which has been continually refined through further ELCAP studies and conferences -- for follow-up tests of any lesions too small to be declared cancerous after only one scan. "Although false-positive CT results are common," she concluded, "they can be managed with little use of invasive diagnostic procedures." Indeed, in a follow-up ELCAP study published last summer in the medical journal Cancer, Henschke reported that with repeat screenings, false positives were uncommon and usually could be corrected without resorting to the dangers of a biopsy of lung tissue.