Key Point

At-risk patients may be able to increase early detection of lung cancer and survival with annual CT scans. Cost-effectiveness of such screenings have yet to be determined.

NEW YORK CITY—A study from researchers of the International Early Lung Cancer Action Program has the potential to change lung cancer screening and treatment for hundreds of thousands of Americans. Claudia I. Henschke, MD, PhD, and colleagues, reported in the October 26 New England Journal of Medicine that low-dose spiral CT scans not only can detect stage I lung cancer, but the 10-year survival rate of those diagnosed with stage I cancer is 88%.¹

This is a marked increase over previous studies. The screening of asymptomatic populations at-risk for lung cancer was not endorsed in May 2004 by the US Preventive Services Task Force, which stated that though existing screening algorithms proved successful in the early detection of lung cancer, there was not enough evidence that mortality was decreased enough when weighed against the invasiveness of the procedures.

A NEW PROTOCOL

Dr. Henschke and colleagues developed a detection and diagnosis protocol that they tested at institutions in the United States, Europe, Japan, Israel, and China. Between 1993 and 2005, 31,567 at-risk people, age 40 or older, underwent baseline screenings. Each institution was allowed to specify its own criteria for enrollment; however, 83% of participants were determined to be at-risk because they were current or former smokers, 11% had exposure to secondhand smoke, and 5% had occupational exposure to asbestos, beryllium, uranium, or radon.

Based on criteria set forth by the research team, including the size and consistency of nodules detected, 4,186 participants required immediate workup as a result of their baseline CT scan. A diagnosis of lung cancer by biopsy or positron-emission tomography followed by biopsy was found in 405 patients. Subjects whose baseline screenings or resultant biopsies came back negative were asked to return in 12 months for another CT scan, with clinicians looking for newly identified noncalcified nodules. A total of 27,456 annual screenings were performed, with 1,460 patients showing new growth, yielding 74 diagnoses of lung cancer. Five interim diagnoses of lung cancer were also reported to the research team, found between screenings due to the development of symptoms.

Of the 484 patients receiving a diagnosis of lung cancer, 411 underwent resection; 57 received radiation, chemotherapy, or both; and 16 received no treatment. The researchers calcuated Kaplan-Meier estimates of lung cancer-specific survival for all participants, regardless of tumor stage and treatment, to be 80% at 10 years. They added, "After the diagnosis of lung cancer was established, the type of intervention, if any, was left to the discretion of the participant and the physician."

Dr. Henschke et al reported that 85% of the lung cancer diagnoses were determined to be stage I. Regardless of treatment, their 10-year survival rate was estimated at 88%. The 10-year survival rate of the 302 patients who decided to undergo resection within one month of diagnosis was 92%. The authors noted that all eight untreated patients died within five years of diagnosis.

A WELCOME ADVANCEMENT IN SPITE OF CAUTIOUSNESS

In an accompanying editorial,² Michael Unger, MD, Director of the Pulmonary Cancer Detection and Prevention Program at the Fox Chase Cancer Center in Philadelphia, praised Dr. Henschke and her colleagues for spearheading the investigation. "The study was a systematic case-control observational study, not the gold-standard randomized trial," said Dr. Unger. "Nevertheless, before the I-ELCAP study, we lacked documentation of the results of a detection test combined with planned management and long-term follow-up."

But he also advised caution in jumping to conclusions about the studies implications. "One of the inherent weaknesses of any single radiographic or biomarker test for lung cancer is the inability to provide unequivocal information about the biology of a tumor—that is, its growth pattern and how it will respond to therapy."

Dr. Unger also questioned the issue of overdiagnosis in the investigators’ final conclusions. "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," he said. "In the short run, chest CT scans alone do not reveal the differences between tumors and growing granulomatous lesions." In addition, centrally-located tumors and tumors in the airway were not readily detectable through CT scans. And despite the assertion by the study’s authors that CT screening is highly cost-effective and comparable to mammography screenings, the editorialist remained wary.

Still, Dr. Unger praised the research team on the study, calling it "a provocative, welcome salvo in the lung struggle to reduce the tremendous burden of lung cancer on society." He cited a public belief that lung cancer is a punishment, not a disease, and suggested that stigma was partially to blame for the drought of investigation into early detection methods to parallel the now routine screenings for breast, colon, cervical, and prostate cancers.

—Jessica Dziedzic

Reference
1. Henschke CI, Yanklelevitz DF, Libby DM, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med. 355;1763-1771.
2. Unger M. A pause, progress, and reassessment in lung cancer screening. N Engl J Med. 355;1822-1824.

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