Prognosis of synchronous and metachronous multiple primary lung cancers: Systematic review and meta-analysis

Background With the development of imaging technology, an increasing number of multiple primary lung cancers (MPLC) are diagnosed in recent years. However, there is still ambiguity in the stage classification rules for patients with MPLC. Our purpose was to access the prognosis of synchronous and metachronous MPLC. Methods A systematic literature search was performed on four databases (EBSCO, Pubmed, OVID and Springer) to obtain relevant articles. We used published hazard ratios (HRs) of overall survival (OS) if available or estimates from the published survival data. Results There were 1796 patients with MPLC in 22 relevant studies, who were eligible for analysis. We found that the OS of patients with synchronous MPLC was inferior to the one of metachronous MPLC patients when starting from the diagnosis of the first metachronous tumor (HR 3.36, 95% CI 2.39–4.74; p < 0.001). However, there was no difference when starting from the diagnosis of the second metachronous tumor (HR 1.19, 95% CI 0.86–1.66; p = 0.29). From further analysis we found the OS of patients with MPLC was superior to that of patients with intrapulmonary metastasis (HR 2.66, 95% CI 1.30–5.44; p = 0.007). Besides, we found no difference in OS between synchronous (HR 1.39, 95% CI 0.98–1.96; p = 0.06) and metachronous (HR 1.05, 95% CI 0.75–1.47; p = 0.77) patients, in spite of the histology. In terms of unilateral and bilateral MPLC patients, the OS had no difference either (HR 1.30, 95% CI 1.00–1.69; p = 0.05). Conclusion We found that MPLC had better OS than the lung cancer patients with intrapulmonary metastasis. And despite the tumor-free interval, the OS for metachronous MPLC was as good as that for synchronous MPLC. Furthermore, there was no difference of OS in different subgroups, including histology and position.