Spiral CT Screening for Lung Cancer Detects Early Curable Disease

NEW YORK, Oct. 25 -- Annual screening of smokers, former smokers and others at risk for lung cancer with low-dose spiral CT can detect early curable disease, asserted investigators in a large international study.

Among more than 31,000 people at risk for lung cancer from smoking or environmental exposure to carcinogens, annual spiral CT screening picked up 484 cases, 85% of which were clinical stage I, with an estimated 10-year survival rate of 88%.

The 10-year survival rate for the 302 participants with clinical stage I cancer who underwent surgical resection within one month after diagnosis was 92%.

So reported Claudia I. Henschke, M.D., Ph.D., of Weill Cornell Medical Center here, and colleagues in the International Early Lung Cancer Action Program (I-ELCAP).

"In a population at risk for lung cancer, such screening could prevent some 80% of deaths from lung cancer," the investigators wrote in the Oct. 26 issue of the New England Journal of Medicine.

"In comparison, in the United States at present, annually approximately 173,000 persons are diagnosed with lung cancer and 164,000 deaths are attributed to this disease, so that approximately 95% of those who are diagnosed with lung cancer die from it."

The relatively low cost of low-dose spiral CT and early surgery compared with treatment for late-stage lung cancer make early screening of an at-risk population cost-effective, the authors contended.

In an accompanying editorial, Michael Unger, M.D., of the Fox Chase Cancer Center in Philadelphia, said that the study adds important information to the debate about the value of widespread screening for lung cancer.

"Unfortunately, we have not left behind the idea that lung cancer is a punishment, not a disease," he wrote. "The legacy of the stigma that has been associated with lung cancer may have delayed the launching of vigorous research on early detection of the disease. The three widely cited studies from the 1970s that failed to show a benefit of the radiographic screening of cigarette smokers did not help matters."

Dr. Unger noted that although widespread screening programs for breast, colon, cervical, and prostate cancers have contributed to lower mortality rates, the U.S. Preventive Services Task Force in 1996 recommended against screening for lung cancer.

"The results of randomized, controlled studies -- the gold standard -- are unavailable, but recommendations based on other studies were formulated, and in 2004, the task force concluded that the evidence was insufficient to make a recommendation for or against the screening of asymptomatic persons for lung cancer," he wrote.

In 1999, the I-ELCAP investigators published in The Lancet results of the ELCAP study, which showed that CT-based imaging was better than traditional radiography at screening for lung cancer, and that the false-positive results could be effectively managed without excess biopsies or thoracotomies.

In their latest work, the investigators conducted a systematic, observational case-control study of screening in 31,567 asymptomatic people at risk for lung cancer who were screened from 1993 to 2005 with low-dose CT.

The cohort included men and women 40-years-old and older who were at risk for lung cancer because of a history of cigarette smoking, or environmental exposure to secondhand smoke, asbestos, beryllium, uranium, or radon. All participants were considered fit to undergo thoracic surgery.

In addition to the 31,567 initial scans, 27,456 repeat scans were performed from seven to 18 months after the previous screening.

The authors estimated 10-year lung cancer-specific survival rates among participants with clinical stage I lung cancer that was detected on CT screening and diagnosed by biopsy, regardless of the type of treatment received. They also estimated survival rates for patients who underwent surgical resection of clinical stage I cancer within one month of diagnosis.

A panel of pathologists examined the surgical specimens obtained from all participants who underwent resection.

The authors estimated survival by calculating Kaplan-Meier curves for lung cancer-specific survival as of the date of diagnosis, irrespective of the type of treatment, including no treatment, for all participants with lung cancer (all stages) and for the subgroup with clinical stage I cancer.

The authors found that screening detected lung cancer in 484 participants, 412 of whom (85%) had clinical stage I disease. The estimated 10-year survival for patients with stage I disease was 88% (95% confidence interval 84% to 91%).

As of last May, 39 of the 412 patients with clinical stage I disease had died of lung cancer. In all, 375 of the 412 underwent surgical resection, 29 had no surgery but received chemotherapy and/or radiation. Eight patients received no treatment.

Among the 302 patients who underwent resection within a month of being diagnosed with cancer, the estimated 10-year survival was 92% (95% CI, 88% to 95%). The eight patients who were not treated all died within five years of diagnosis.

The authors noted that the 1.3% detection rate of lung cancer on baseline screening was slightly higher than that for baseline mammography (0.6% to 1.0%), and the annual screening detection rate of 0.3% was on a par with that of annual screening for breast cancer among women 40 and older (0.2% to 0.4%).

"The rate of cancer detection depends on the risk profile of those undergoing screening; the higher the risk, the more productive the screening," the I-ELCAP investigators wrote. "Thus, as expected, CT screening of the original participants in ELCAP, who were former and current smokers 60 years of age and older, was more productive in detecting lung cancer (detection rates, 2.7% on baseline screening and 0.6% on annual screening) than among participants in the expanded study."

They also noted that the cost of low-dose CT is below , and that the cost of surgery for stage I lung cancer is less than half that of late-stage treatment.

"Using the original ELCAP data and the actual hospital costs for the workup, we found CT screening for lung cancer to be highly cost-effective," they wrote. "Other estimates of the cost-effectiveness of CT screening for lung cancer for various risk profiles a re similar to that for mammography screening."

In his editorial, Dr, Unger wrote that "the I-ELCAP study has considerable merit, but important questions remain. It is possible that without consideration of tumor biology, biases such as lead time and overdiagnosis could have been introduced in the final analysis of mortality. In the short run, chest CT scans alone do not reveal the differences between tumors and growing granulomatous lesions. Moreover, centrally located tumors or tumors located in the airway are not readily detectable by means of CT scanning. The question of cost-effectiveness remains unanswered."

"These are very exciting findings that show real promise for reducing this country's top cause of cancer death," said Robert A. Smith, Ph.D., director of screening for the American Cancer Society.

"But health policy isn't made on the basis of one study, or by one organization. In an era of evidence-based medicine, it is a collective process. It is quite reasonable to be enthusiastic about these findings, and yet still recognize that the weight of expert opinion about the efficacy of lung cancer screening will require results from the on-going prospective randomized trials, including the National Lung Screening trial (NLST), from which experimental results are expected before the end of the decade."