Compared with usual care, the use of annual chest radiographs as a screening tool for lung cancer did not reduce lung cancer mortality in the large, randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
The results dovetail with findings published earlier this year from the NLST (National Lung Screening Trial), which demonstrated a 20% mortality advantage with computed tomography screening vs. chest radiograph screening (N. Engl. J. Med. 2011;365:395-409), according to Dr. Martin M. Oken of the University of Minnesota, Minneapolis, and his colleagues from the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) Project Team.
It follows that CT screening also has a similar advantage over usual care, the investigators said.
In the PLCO trial, the cumulative incidence rates of lung cancer after 13 years of follow-up were 20.1 and 19.2 per 10,000 person-years in the 77,445 trial participants randomized to receive screening with annual chest radiographs and the 77,456 participants assigned to usual care, respectively (relative risk, 1.05). The number of lung cancer deaths was 1,213 in the radiograph group and 1,230 in the usual care group, for cumulative incidence rates of 14.0 and 14.2 per 10,000 person-years, respectively (RR, 0.99), they reported online in the Oct. 26 issue of JAMA.
The lung cancer mortality relative risks were 0.94 for never smokers, 1.02 for former smokers, and 0.99 for current smokers, and for men and women, respectively, they were 1.02 and 0.92.
In a subset of 15,183 intervention patients and 15,138 usual care patients from the PLCO trial who would have met eligibility criteria for the NLST, which was initiated 9 years after the PLCO trial, the cumulative lung cancer incidence rates per 10,000 person-years through 6 years of follow-up were 60.6 and 60.8 in the groups, respectively, the investigators also noted.
Cumulative lung cancer mortality rates in that subset of patients were 36.1 and 38.3 per 10,000 person-years in the radiograph and usual care groups, respectively (RR, 0.94).
"The corresponding [relative risk] for the total PLCO cohort at 6 years was 1.02 for lung cancer incidence and 0.91 for lung cancer mortality," the investigators said.
The PLCO findings, which were published simultaneously with their presentation at CHEST 2011, not only facilitate interpretation of the NLST results, but also "provide important information about the benefits and harms of annual chest radiographic screening," the investigators said, noting that although there were some modest differences between the PLCO and NLST cohorts, "it seems reasonable to consider the chest radiograph vs. usual care comparison in the NLST-eligible cohort in the PLCO to be an adequate surrogate for such a comparison with NLST (JAMA 2011 Oct. 26 [doi:10.1001/jama.2011.1591]).
"As such, the 20% mortality benefit of low-dose spiral CT vs. chest radiograph observed in NLST is likely a good approximation for the mortality benefit that must have been observed of low-dose spiral CT vs. usual care if this latter group had been added to NLST," they said.
PLCO participants were adults aged 55-74 years who were randomly assigned between November 1993 and July 2001 to receive annual screening with posterior-anterior view chest radiographs for 4 years or usual care, which included their usual medical care with no interventions. Adherence to the assigned screening protocol was 86.6% at baseline and 79%-84% at years 1-3. In the usual care group, an estimated 11% (the "contamination rate") underwent chest radiograph screening.
The primary treatment for lung cancer in both groups was similar: The predominant therapy for stage I and II non–small cell lung cancers was resection without chemotherapy, and for stage III or IV non–small cell lung cancers, the predominant therapy was chemotherapy without resection, the investigators noted.
"The randomized groups in the 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. Therefore, these findings provide good evidence that there is not a substantial lung cancer mortality benefit from lung cancer screening with 4 annual chest radiographs," the investigators wrote.
The PLCO Cancer Screening Trial was funded by the National Cancer Institute (NCI) and was also supported by contracts from the NCI’s Division of Cancer Prevention and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics NCI, National Institutes of Health, Department of Health and Human Services. Several authors disclosed potential conflicts of interest, including financial relationships with a number of pharmaceutical companies; the complete list of disclosures is provided in the JAMA article.