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West J Med. Apr 2001; 174(4): 230–231.
PMCID: PMC1071335

Spiral computed tomography screening

Study begins to determine its efficacy in lung cancer prevention

Lung cancer is one of the leading causes of cancer-related deaths in both men and women in the world. This year, in the United States alone, an estimated 164,000 new cases of lung cancer will be identified, and the disease will cause 156,000 deaths. Despite major efforts to improve cancer treatment over the past 20 years, progress has been modest. Nearly 90% of cases of lung cancer is attributable to cigarette smoking. Avoiding uptake of the habit would be an effective means of primary lung cancer prevention. Although smoking cessation lowers risk, the large population of former smokers remains at risk for lung cancer. Therefore, the development of an effective secondary prevention tool for lung cancer screening, if proved to decrease mortality from the disease, would be of great public health importance.

The strongest evidence regarding screening efficacy would come from a randomized clinical trial (RCT) with cancer-specific mortality as the end point.1 Screening for lung cancer with chest radiography with and without sputum cytology was not shown to be effective in the 3 National Cancer Institute (NCI)-sponsored RCTs in the 1970s that addressed their utility.2 The Mayo Lung Project (MLP) is the most representative of the trials. The MLP was a randomized screening trial of chest x-ray and pooled sputum cytologic examination every 4 months versus usual care, which consisted of a recommendation to have annual chest radiography and sputum cytologic examination (but without further efforts to achieve adherence to the recommendation). After an initial prevalence screen, 9,211 high-risk participants (men only) were randomly allocated: 4618 to the screened group and 4583 to the control group. There was an increase in the number of cancers detected in stage I and II in the screened arm (206 vs 160). Interestingly, the actual number of cases detected at late stage was comparable. This led to a large improvement in 5-year survival in the screened group (31% vs 13%). Nevertheless, the lung cancer death rate was virtually identical in both groups (3.2 vs 3.0 per 1,000 person-years). Even after prolonged study follow-up, lung cancer mortality was virtually the same in both study arms, despite substantially better survival time after diagnosis of lung cancer in the screened arm of the study. An update by Marcus et al at the NCI with follow-up to 25 years confirmed this.3 Total mortality in the study arms was identical, demonstrating good distribution of risk factors as a consequence of the randomization. This trial shows good evidence of overdiagnosis: tumors that do not come to attention in the absence of screening efforts. The MLP was designed to have a 90% power to detect a 50% reduction in lung cancer mortality. Because a more realistic reduction in mortality may have been missed, the NCI is now conducting the large-scale Prostate, Lung, Colorectal and Ovarian (PLCO) trial. More than 142,000 of the accrual goal of 148,000 participants have been enrolled.

The Early Lung Cancer Action Project (ELCAP) published their results of a baseline prevalence screen with spiral computed tomography (CT), which revealed an impressive relative increase in the proportion of lung cancer cases at early stages and an increased detection rate compared with chest radiography.4 Two earlier studies had looked at the utility of spiral CT in Japanese groups with similar results.5,6 None of these studies was controlled. In ELCAP, 1,000 high-risk, symptom-free volunteers had a screening chest radiograph and spiral CT. The Lancet reported on the results in individuals with 1 to 6 noncalcified nodules. More diffuse abnormalities and 4 tumors diagnosed at a later stage were excluded from analysis. Spiral CT detected 1 to 6 noncalcified nodules in 233 (23%) participants. Chest radiography detected 1 to 6 noncalcified nodules in 68 (7%) participants. Twenty seven participants had malignancy diagnosed, and only 7 of these were detectable on chest radiographs. Twenty three (85%) of these malignant lesions were stage I (Surveillance, Epidemiology, and End Results [SEER] distribution 22%). Twenty-one of the malignant noncalcified nodules were adenocarcinomas, twice the expected distribution. Although this information is valuable, an increased yield of stage I lung cancers, as shown in MLP, does not necessarily translate into a mortality reduction. Nonrandomized trials of screening modalities cannot readily account for lead time, length bias, or overdiagnosis bias. A large RCT with a mortality end point is required to assess the effectiveness of this technology. Before making public health recommendations, a strong knowledge of net benefit versus forms of early diagnosis and resulting treatment is required on both medical and ethical grounds.7

For these reasons, the NCI is planning to conduct a multicenter RCT of lung cancer screening with low-dose spiral CT scanning in current and former cigarette smokers. The primary end point will be lung cancer mortality. In preparation for such a trial, the NCI is planning a randomized feasibility study of several thousand participants designed to evaluate the willingness of subjects to be randomly allocated to different treatments, to determine the rate of abnormal results, and to estimate some of the operating characteristics of spiral CT in the screening setting. The feasibility study is underway.

Figure 1
Color computed tomographic scan of the thorax showing a carcinoma of the left main stem bronchus [Fraser/SPL]


Competing interests: None declared


1. Prorok PC, Kramer BS, Gohagan JK, eds. Screening Theory and Study Design: the Basics in Cancer Screening. New York, NY: Marcel Dekker, 1999: 29-53.
2. Wolpow DR. Early detection in lung cancer: case finding and screening. Med Clin North Am. 1996;80: 63-82. [PubMed]
3. Marcus P, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality in the Mayo Lung Project: the impact of extended follow-up. J Natl Cancer Inst 2000;92: 1308-1316. [PubMed]
4. Henschke C, McCauley D, Yankelevitz D, et al. Early lung cancer action project: overall design and findings from baseline screening. Lancet 1999;354: 99-105. [PubMed]
5. Shusuke S, Shodayu T, Feng L, et al. Mass screening for lung cancer with mobile spiral computer tomography scanner. Lancet 1998;351: 1242-1245. [PubMed]
6. Kaneko M, Eguchi K, Obmasu H, et al. Peripheral lung cancer: screening and detection with low-dose spiral CT versus radiography. Radiology 1996;201: 798-802. [PubMed]
7. Malm H. Medical screening and the value of early detection: when unwarranted faith leads to unethical recommendations. Hastings Cent Rep 1999;29: 26-37. [PubMed]

Articles from The Western Journal of Medicine are provided here courtesy of BMJ Group
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