Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers

Abstract Objective Multiple primary lung cancers are detected with increasing frequency, but the ideal strategy for diagnosis and treatment remains disputable. This study evaluated both clinical characteristics and genetic alterations to investigate the appropriate strategy for patients with multiple primary lung cancer. Methods A total of 96 patients in our practice were diagnosed with multiple primary lung cancer over 7 years by clinical-pathologic criteria. According to consolidation/tumor ratio, they were classified into 3 groups: group A (multiple ground-glass opacity–dominant nodules, consolidation/tumor ratio ≤0.5), group B (1 solid-dominant nodule, consolidation/tumor ratio >0.5 with other ground-glass opacity–dominant nodules), and group C (2 solid-dominant nodules). A series of somatic genetic mutations and fusions were analyzed in a portion of the patients. Results There were 24, 35, and 37 patients in groups A, B, and C, respectively. During follow-up, 23 patients had recurrence. The 5-year recurrence-free survival was 100% in patients with multiple ground-glass opacity, 68% in those with 1 solid lesion, and 51.4% in those with 2 solid tumors ( P  = .001). Eighteen patients died of lung cancer. The 5-year overall survival was 100% in group A, 80.5% in group B, and 59.9% in group C ( P  = .002). A total of 77 driver mutations were detected in 61 of the 82 lesions. A high rate of discordance of genetic alterations (89.7%) was found between cancers within individual patients. Two patients in group C had concordant driver mutations between the 2 lesions, and both of them harbored tumor recurrence. Conclusions A high discordance of driver mutations between tumors in individual patients and a favorable prognosis were identified in patients with multiple primary lung cancers diagnosed by clinical-pathologic criteria, which support different strategies from those with metastatic disease.