Patterns of Distant Metastases in Surgically Managed Early-Stage Non-Small Cell Lung Cancer

Abstract

Metastatic progression is a major competing risk in lung cancer mortality. Treatment of oligometastatic non-small cell lung cancer (NSCLC) with local therapies, including surgery or radiation therapy, is controversial, although for some sites there is reasonably good data to support such therapies in select patients. The number of patients that present with oligometastatic NSCLC after surgery is not well defined. Our objective was to quantify the rate and location of distant metastases (DM) and determine the number of patients potentially eligible for metastasis-directed therapy. A database of surgically managed early-stage NSCLC patients from 1995-2008 utilizing REDCap electronic data capture tools was reviewed. All information pertaining to development of the first distant progression was recorded and subsequently analyzed. Sites of DM were categorized into parenchymal lung, liver, adrenal, bone, brain, extrathoracic lymph nodes, pleural/pericardial effusion or other. Lesions were categorized as solitary, oligometastatic (1-3) or diffuse (>3 or untreatable metastases such as malignant pleural effusion) for further analysis. Of the 1,727 patients, 370 (21%) developed DM. Detection was based on symptoms in 52%, surveillance imaging in 43% and indeterminate in 5% of patients. Of those who developed DM, 175 (47%) were associated with local progression, the majority of which were synchronous (125, 71%). The median time to developing DM was 12 months (range, 0-188 months), and the average number of metastatic sites was 1.56 ± 0.09 (95% CI). Metastatic sites in order of decreasing frequency were bone (120, 32%), lung (116, 31%), brain (107, 29%), liver (67, 18%), adrenal (54, 15%), extrathoracic lymph nodes (45, 12%), pleural/pericardial effusion (28, 7%) and other (38, 10%). Of the 370 patients, 33% had a solitary and potentially treatable metastatic lesion. An additional 19% had 2-3 lesions amenable to therapy (52% oligometastatic overall). The median size of oligometastatic lesions was 20 mm (range, 3-110 mm). Of patients that received neoadjuvant or adjuvant chemotherapy as part of their initial treatment, 58% had an oligometastatic progression vs 49% with no chemotherapy (p = 0.14). Distant progression is common in early stage lung cancer, with surveillance imaging detecting a significant proportion of cases. Oligometastasis is a common pattern of the first distant failure. Clinical trials investigating metastasis-directed therapy should be pursued.