Abstract: With the widespread implementation of lung cancer screening, more and more patients are being diagnosed with multiple primary lung cancers (MPLCs). In the era of precision medicine, many controversies remain in differentiating MPLCs from intrapulmonary metastasis and the optimum treatment choice, especially in patients exhibiting similar histology. In this review, we summarize common diagnostic criteria and novel discrimination methods with a special emphasis on the emerging value of broad panel next-generation sequencing (NGS) for the diagnosis of MPLCs. We then discuss current advances regarding therapeutic approaches for MPLCs. Radical surgery is the main treatment modality, while stereotactic body radiotherapy (SBRT) is safe and feasible for early-stage MPLC patients with inoperable tumors. In addition, immunotherapy and targeted therapy, particularly epidermal growth factor receptor-tyrosine kinase inhibitors, are emerging therapeutic strategies that are still in their infancy. Characteristics of both genomic profiles and tumor microenvironment are currently being evaluated but warrant further exploration to facilitate the application of targeted systematic therapies in MPLC patients.
Keywords: multiple primary lung cancers, MPLCs, diagnosis, surgery, stereotactic body radiation therapy, SBRT, targeted therapy, immunotherapy