Image source: Software-processed (bone-suppressed) chest x-ray with nodule in right upper lung. Source: Radiology.

Annual chest x-ray screening did not lower the rate of death from lung cancer compared with usual care, according to a study of more than 150,000 participants to be published Nov. 2 in the Journal of the American Medical Association. The study demonstrated that chest x-ray screening is not effective and set the stage for comparing CT screening to usual care, Harold C. Sox, MD, of Dartmouth Medical School in West Lebanon, N.H., wrote in an accompanying editorial.

Studies examining lung cancer screening stretch back four decades. However, researchers had not determined the effect of chest x-ray on lung cancer mortality.

Martin M. Oken, MD, of the University of Minnesota in Minneapolis, and colleagues examined the effect on mortality of screening for lung cancer using chest x-ray in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The randomized controlled trial involved 154,901 participants, ages 55 through 74 years, of whom 77,445 were assigned to annual screenings and 77,456 to usual care, at one of 10 screening centers across the U.S., between November 1993 and July 2001. The groups were similar: approximately half were women (50.5 percent); about 45 percent were never smokers, 42 percent former smokers and 10 percent current smokers.

Participants in the intervention group were offered an annual chest x-ray for four years. Diagnostic follow-up of positive screening results was determined by participants and their healthcare providers. Participants in the usual care group were not offered chest x-ray screening and received their usual medical care. All diagnosed cancers, deaths and causes of death were ascertained through the earlier of 13 years of follow-up or until Dec. 31, 2009.

During the entire 13-year study period, there were 1,696 lung cancers detected in the intervention group and 1,620 lung cancers in the usual care group. Of participants diagnosed with lung cancer during the follow-up, stage and histology was similar by group, with about 41 percent being adenocarcinoma, 20 percent squamous cell carcinoma, 14 percent small cell carcinoma, 5 percent large cell carcinoma and 20 percent other non-small cell lung cancer.

Regarding the effect on mortality, the researchers found that annual chest x-ray screening for up to four years did not significantly decrease lung cancer mortality compared with usual care: for the total 13-year follow-up period, 1,213 lung cancer deaths were observed in the intervention group versus 1,230 in the usual care group.

The researchers also conducted an ancillary analysis of the subset of PLCO participants who would have been eligible for the National Lung Screening Trial (NLST). This subset included 15,183 participants in the chest x-ray group and 15,138 in the usual care group. Rates of lung cancer cases and lung cancer deaths were similar in both groups. In the chest x-ray group, 518 participants were diagnosed with lung cancer and 316 deaths occurred. In the usual care group, there were 520 lung cancer cases and 334 deaths.

“The randomized groups in PLCO were comparable at baseline, there was relatively high screening adherence in the intervention group and low contamination in the usual care group, and the treatment distributions across the groups were similar,” Oken and colleagues wrote. "Therefore, these findings provide good evidence that there is not a substantial lung cancer mortality benefit from lung cancer screening with four annual chest radiographs."

In the editorial, Sox noted that most of the 1,696 cancers in the PLCO trial were interval cancers, arose in patients who were never screened or arose in patients who had completed three rounds of screening.

The study, he wrote, should put the question of the effectiveness of x-ray screening for lung cancer to rest and also points to the need for a comparison of low-dose CT screening with usual care.