Lung Cancer Screening and the National Debt

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips serves on the speaker's bureau of Cephalon, Boehringer Ingelheim, Merck, ResMed, and GlaxoSmithKline, and is a consultant for Boehringer Ingelheim, Wyeth-Ayerst, and ResMed.

Synopsis: Annual CT scanning of at risk people can detect early (Stage 1) lung cancers and perhaps reduce the mortality rate of lung cancer in this group.

Source: The International Early Lung Cancer Action Program Investigators. Survival of Patients with Stage 1 Lung Cancer Detected on CT Screening. N Engl J Med. 2006;355:1763-1771.

This paper is the product of a 12-year, multi-center, multi-country observation of more than 31,000 people who were at risk for lung cancer. In this study, "at risk" people were those over 40 with a history of active or passive smoking or with occupational exposure (beryllium, asbestos, uranium, or radon). Overall, 83% of the participants were current or former smokers; smoking was less likely to be the risk factor for those participants from Japan.

For the initial baseline screen, a positive screening CT was defined by the presence of a solid or partly solid calcified nodule > 5 mm, a nonsolid, noncalcified nodule > 8 mm, or a solid endobronchial nodule. In this cohort of 31,567 at risk people, 4186 people had an initial positive screen. The workup for these positive CT scans varied, but culminated in fine needle aspiration biopsy if the nodule grew on subsequent CT's (usually within 3 months). Of the more than 4000 people with positive initial screens, 405 were found to have lung cancer. Five of those with initial negative screens had lun,g cancer diagnosed after work-ups that were prompted by symptoms.

Those with negative screening CT's (27,381) had repeat screening CT scans at 12-month intervals (though the variability of this in actual practice was 7-18 months). For these follow-up annual screens a positive screening was considered to be any new noncalcified nodule. Over the time course of this study (about 12 years), 1460 of these individuals developed positive CT scans, and 74 of those with positive scans were diagnosed with lung cancer.

Work-ups for positive CT scans and treatment of any diagnosed cancer were variable, depending on the patient and the attending physician. In point of fact, only 535 (about 10%) of those patients with positive scans ended up having biopsies. The diagnosis of lung cancer for inclusion in this study required a pathologic examination that was read in the central reading center. Ten-year survival curves were constructed for the participants.

Overall, then, 405 of the 31,567 (1.3%) participants were found to have cancer over the time course of this study. Adenocarcinoma subtypes were, far and away, the most common kind of cancer diagnosed. The estimated 10 year survival rate of all study participants with lung cancer was 80%. Of the cancers diagnosed in this study, 85% were stage 1, and the 10-year survival rate of this group was 88%. Of the 405 participants diagnosed with cancer during this study, 302 underwent resection within a month of diagnosis, and these people had a 92% survival rate. In their discussion, the authors note that the cost of a low-dose screening CT scan is below $200 and that the cost of surgical resection of stage 1 cancer is less than that of advanced cancer. They state that the cost-effectiveness of CT scanning for those at risk for lung cancer is "similar to that for mammography screening."

Commentary

This paper has received attention in the lay press (and was published in the New England Journal!), so our patients are likely to be asking about it. In her column in US News and World Report, Dr. Bernadine Healy pointed out that lung cancer kills more patients than do cancers of the breast, prostate, colon, and cervix combined, and exhorts …"we may finally have an early-detection option. …Let's get on with it."1

The rationale for the current study and for formation of The Early Lung Cancer Action Project (ELCAP) is to pick up symptomatic cancers when they are in early stages, and thus more amenable to cure. The survival results reported here are remarkable, but they are not truly new. Previous, smaller studies have shown that picking up cancers earlier can result in a higher cure rate.2-5

To understand this issue better, we reviewed this paper at the journal club of the Pulmonary Division at the University of Kentucky College of Medicine. We Kentuckians know lung cancer, since Kentucky typically leads the nation in smoking prevalence and (duh) lung cancer. Right away, it was obvious that this is a contentious issue, with one faculty member saying, "It's remarkable that so much effort and money continues to be invested in something that is almost completely preventable," and another faculty member saying, "If this were about breast cancer, everybody would be on the bandwagon and screening CT's would be covered and encouraged by insurance companies."

As we dissected the paper, we became confused about how many "annual exams" each participant in this study may have had, and we noted that it was not possible to tell how many patients had PET scans or what the criteria were that led to biopsy.

It was also pointed out that this study is not the definitive study of early detection of lung cancer. As with many other aspects of medical science, a randomized, controlled trial will yield a much more definitive answer. Fortunately, such a trial is underway. The National Lung Screening Trial (NLST), sponsored by the National Cancer Institute is ongoing.6 This trial is comparing spiral computed tomography (CT) and standard chest X-ray to show if either test is better at reducing lung cancer deaths. As of February 2004, nearly 50,000 current or former smokers had joined NLST at more than 30 study sites across the country. The trial is now closed to further enrollment, and will collect and analyze data for eight years. As is pointed out on the NLST web site, "… no scientific evidence to date has shown that screening or early detection of lung cancer actually saves lives. … Some studies have shown that spiral CT detects smaller abnormalities than chest x-ray. However, smaller cancers are not always 'early' cancers, and we do not know if detecting these small abnormalities and treating them will reduce lung cancer deaths. To address this question, it is necessary to conduct a randomized, controlled clinical trial as we are doing in NLST."

So, how do we manage "at risk" patients in the meantime? First of all, patients need to know that, at present, they will need to pay for screening CT's out of pocket. They also need to know that having a screening CT could open Pandora's Box. In the ELCAP study, the rate of false-positive CT scans was quite high: about 10% of those with an initial positive scan had cancer, and only about 5% of those with a subsequent positive annual scan had cancer. This is a lot of repeat CT scans, PET scans, or biopsies. And perhaps angst.

References

1. Healy B. To have and have not. US News and World Report. Nov 13, 2006, p. 66.

2. Sobue T, et al. Screening for lung cancer with low-dose helical computed tomography: anti-lung cancer association project. J Clin Oncol. 2002;20:911-920.

3. Buell PE. The importance of tumor size in prognosis for resected bronchogenic carcinoma. J Surg Oncol. 1971;3:539-551.

4. Martini N, et al. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg. 1995;109:120-129.

5. Henschke CI, et al. Screen-diagnosed small stage I cancers of the lung: genuineness and curability. Lung Cancer. 2003;39:327-330.

6. www.cancer.gov/nlst. Accessed Nov 28, 2006.