Patients with primary lung cancer detected with low-dose computed tomography (LDCT) screening have a lower risk of developing brain metastases than patients whose cancer was detected through other methods, researchers found.

After adjusting for age at diagnosis, cancer stage, histology, and smoking status, patients whose lung cancer was detected with LDCT screening had a significantly lower 3-year incidence of brain metastases (6.5%) compared with patients whose cancer was detected through chest x-ray screening, incidental detection, or clinical symptom-based detection (11.9%), with a cause-specific HR of 0.53 (P=0.001), reported Summer Han, PhD, of Stanford University School of Medicine in California, and colleagues in the Journal of Thoracic Oncology.

“LDCT screening for primary lung cancer may be beneficial for reducing brain metastases risk,” in addition to “early detection of primary lung cancer and lung cancer-specific mortality reduction as already shown in the National Lung Screening Trial,” Han told MedPage Today.

Patients with lung cancer who are diagnosed with brain metastases have poor survival, with most surviving only 3 or 4 months after diagnosis, the researchers said. However, patients who have well-controlled or asymptomatic brain metastases have better survival, indicating the importance of early detection.

Han and colleagues used data from the large, prospective, population-based, randomized National Lung Screening Trial. The study included 1,502 patients diagnosed with primary lung cancer (median age 65.9 years at time of diagnosis) from 2002 to 2009 with follow-up data available on brain metastases.

Of these patients, 76.8% had early-stage primary lung cancer, 41.8% had adenocarcinoma, and 55% had undergone surgery as primary treatment. When broken down by mode of detection, 41.4% had their cancer detected by LDCT screening compared with 58.6% whose cancer was detected by other methods.

The 3-year cumulative incidence of brain metastases after a lung cancer diagnosis was 9.4% for the entire cohort.

The reduction in bone metastases risk among lung cancers detected with LDCT screening persisted among subgroups. For example, there was an even more pronounced reduced risk of brain metastases with LDCT screening among patients with early-stage (I-III) primary lung cancer (HR 0.47, 95% CI 0.29-0.75, P=0.002), and when cancers were further restricted to stage I and II (HR 0.35, 95% CI 0.18-0.68, P=0.002).

The same held true for the subgroup of patients who underwent surgery for primary lung cancer (HR 0.37, 95% CI 0.21-0.68, P=0.001).

This reduction in risk for brain metastases among lung cancers detected by LDCT, which persisted in these subgroup analyses, “may not be fully explained by stage shift nor curative treatment for primary lung cancer,” wrote Han and colleagues.

In an exploratory imaging analysis, the researchers demonstrated that tumors detected with LDCT screening were different in nodule size and with respect to margins.

“We believe that a possible explanation for the observed reduction in the risk of brain metastases — even when restricted to early-stage primary lung cancers — is that the tumors detected by LDCT screening may have a potentially different tumor biology that are slower growing and less aggressive compared with those detected otherwise, although this needs to be confirmed by further investigation,” Han said.

Andrea McKee, MD, chief of the division of radiation oncology at Lahey Hospital and Medical Center in Burlington, Massachusetts, told MedPage Today that she and her colleagues are seeing comparable results at their institution. “But, we suspect it has more to with the size of the lesion, not that they are more indolent,” she said. “The only way to really know about the biological basis of these tumors would be to do a path analysis.”

“What would really be interesting would be to see this reported not only by stage, but by sub-stage,” added McKee, who was not involved in the study. “We’re not just detecting early-stage lung cancer — we’re detecting the earliest of the early-stage cancers, and we suspect that is what makes the difference.”

The study’s major takeaway is clear, she said. “Basically, keep screening. Let’s not [have to] treat brain metastases.”