Clinical outcomes of patients with metachronous second primary lung adenocarcinomas

BACKGROUND The incidence of adenocarcinomas as multiple primary lung cancers (MPLCs) is increasing. How to determine the treatment strategies of MPLCs, especially second primary lung adenocarcinomas (SPLACs), and the prognostic factors associated with it are unclear. METHODS The clinical records of patients undergoing surgery for second adenocarcinomas based on Martini-Melamed criteria between 2001 and 2014 were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was conducted using the Cox proportional hazards model. RESULTS A total of 115 patients with SPLACs were identified based on Martini-Melamed criteria. With respect to the second resections, three subgroups with low- (adenocarcinoma in situ, n=6; minimally invasive adenocarcinoma, n=19), intermediate- (lepidic, n=9; acinar, n=40; papillary, n=23), and high-grades (solid, n=9; micropapillary, n=2; invasive mucinous, n=7) were assigned. The 5-year overall survival (OS) rates from the time of the first and the second resections were 86.5% and 69.5%, respectively. Cox multivariate analysis identified computed tomography (CT) morphology of SPLACs (ground glass opacity predominant versus solid predominant; hazard ratio [HR]=0.42; P=0.036), histologic classification (same/similar vs different; HR=0.06; P<0.001), pathologic stage of the primary (stage I vs II; HR=0.20; P=0.015) and second tumors (stage I vs IIIa; HR=0.21; P=0.002), and histologic grade of SPLACs (low- vs high-grade, HR=0.05, P=0.016; intermediate- vs high-grade, HR=0.37, P=0.027) as significantly favorable prognostic factors for OS. CONCLUSION In addition to pathologic stage of the initial tumors and histologic classification, pathologic stage and CT morphology of SPLACs were identified as predictors of survival. The histologic grade of SPLACs based on the new adenocarcinoma classification could provide additional prognostic information.