Impact of Contralateral Tumor Nodules on Survival in Non-Small Cell Lung Cancer: A SEER Database Analysis

Abstract

Purpose/Objective(s): We explored the prognostic implications of contralateral tumor nodules in patients with non-small cell lung cancer (NSCLC) using the SEER database. We hypothesized that many such cases represent a second primary tumor and exhibit a favorable prognosis compared to other types of metastatic disease. Materials/Methods: We analyzed overall survival (OS) in SEER data from 2004-2009 for patients age 25-85 with malignant primary tumors of the lung or bronchus and non-small cell histology. Patients were categorized as M0, M0 with ipsilateral nodule in separate lobe, M1a with contralateral nodule, M1a without contralateral nodule, or M1b with distant metastasis. We used Kaplan-Meier estimates and the log-rank test to compare OS between groups. Using a proportional hazards model, risk of death for patients with tumor nodules in a contralateral lobe was compared to what would be expected from a synchronous second primary tumor. Results: Of 208,691 patients who met inclusion criteria, 10,548 had contralateral tumor nodules without other metastatic disease. Median and 2 yr OS for these patients was 7 mo and 18%, respectively. This was greater than that observed in patients with other forms of M1a disease (4 mo and 8%; p < 0.001) but less than that with an ipsilateral nodule in a separate lobe (11 mo and 27%; p < 0.001). This pattern persisted when patients were stratified by N-stage and primary tumor size. Not unexpectedly, patients with ipsilateral nodules received more definitive treatment relative to those with contralateral nodules (21% surgery, 30% radiation vs 6% surgery, 23% radiation). Interestingly, patients with T1-2a N0-1 disease and a contralateral nodule achieved greater OS than those with no additional pulmonary nodule but with N3 disease. Patients with T1-2N0 disease and a contralateral nodule had a hazard for death that was not significantly different from that expected from a synchronous stage IA primary tumor. Patients with more advanced T and N stages had OS intermediate between that estimated for concurrent primaries and M1b disease. Conclusions: Contralateral tumor nodules in NSCLC carry a prognosis more favorable than other M1a or M1b disease but less favorable than no additional nodule or an ipsilateral nodule in a separate lobe. Collectively, our analyses suggest that M1a contralateral nodules represent two distinct biological subgroups: hematogenous metastatic disease and synchronous, early stage second primaries. This study points to (1) an opportunity for improvement in the current staging system, (2) a rationale for definitive treatment of T1-2N0 patients with contralateral nodules, and (3) a need for molecular pathologic sub-classification of contralateral pulmonary nodules in patients with more advanced disease in order to identify those who may benefit from aggressive loco-regional treatments. Author Disclosure: Z.S. Morris: None. D.M. Cannon: None. S.M. Bentzen: None. K.R. Kozak: None.