Commentary: Early Diagnosis of Lung Cancer: Where Do We Stand?

Abstract

Lung cancer is the leading cause of cancer deaths worldwide [1]; approximately 85% of all lung cancers occur in current or former cigarette smokers [2]. Recently, two important studies [3, 4] received worldwide press coverage for the discordant results reported [5–8]. The critical issue was whether spiral computed tomography (CT) scan screening could reduce lung cancer deaths in heavy cigarette smokers and could thus be considered the ultimate test of any effective cancer screening. The first study [3] reported that low-dose CT screening could lead to a therapeutic strategy that resulted in a 10-year survival rate of 88% for patients with stage I disease. The authors, in a large collaborative study, screened 31,567 asymptomatic persons at risk for lung cancer using lowdose CT; 27,456 repeated screenings were performed 7–18 months after the previous screening. They estimated the 10year lung cancer–specific survival rate 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, and among those who underwent surgical resection of clinical stage I cancer within 1 month. Screening resulted in a diagnosis of lung cancer in 484 participants. Of these participants, 412 (85%) had clinical stage I lung cancer, and the estimated 10-year survival rate was 88% in this subgroup (95% confidence interval [CI], 84%–91%). Among the 302 participants with clinical stage I cancer who underwent surgical resection within 1 month after diagnosis, the survival rate was 92% (95% CI, 88%– 95%). The eight participants with clinical stage I cancer who did not receive treatment died within 5 years after diagnosis. The second study reported that there is no evidence that screening with chest CT scan does anything to reduce lung cancer deaths [4]. Those investigators used a validated lung cancer prediction model to estimate the expected numbers of various lung cancer outcomes among the combined cohort of 3,246 participants. To assess the effectiveness of CT screening, they then compared the observed numbers of lung cancer outcomes with the numbers of expected cases. They observed a more than threefold higher number of new lung cancer cases (144 observed versus 44.5 expected) and a tenfold higher number of lung cancer resections (109 observed versus 10.9 expected). However, there were no fewer advanced lung cancer cases (42 observed versus 33.4 expected) or lung cancer deaths (38 observed versus 38.8 expected). Several limitations of the first study [3] have to be highlighted: (a) the data used were the baseline examination and first CT repeat; (b) the specific survival rate was reported for 412 (1.3%) clinical stage I patients; (c) survival in the vast majority of subjects after 2 years is not valuable; (d) deaths related to surgery were reported within 4 weeks, whereas the standard is 30 days [9]; and (e) biopsies were performed in 535 of the 5,646 participants (9.5%) with positive results on chest CT. The limitation of the second study [4] is that the investigators used a validated lung cancer prediction model to estimate the expected numbers of various lung cancer