Diagnosis and Selection of Surgical Approaches for Synchronous Multiple Primary Lung Cancer: A Narrative Review

Background and Objective: Synchronous multiple primary lung cancer (SMPLC) is a distinct clinical entity in lung cancer management. Because SMPLC differs substantially from intrapulmonary metastasis (IPM) in staging, treatment strategy, and prognosis, accurate assessment of the clonal relationship among multiple malignant pulmonary lesions is essential for treatment planning. This narrative review summarizes the diagnostic basis, preoperative assessment, and selection of surgical approaches for SMPLC and discusses bilateral surgery, residual ground-glass nodules, and future research directions.

Methods: PubMed was searched for English- or Chinese-language publications from 1 January 2000 to 18 August 2026 using terms related to SMPLC, IPM, molecular clonality, lobectomy, segmentectomy, wedge resection, bilateral surgery, subsolid nodules, and local therapy. An update search was performed during revision to capture recent literature on molecular clonality, bilateral video-assisted thoracoscopic surgery (VATS), and residual ground-glass nodules. Relevant guidelines, reviews, cohort studies, systematic reviews, case series, and representative case reports were selected according to their relevance to the clinical scope of this review. No formal risk-of-bias assessment or quantitative synthesis was performed.

Key Content and Findings: Traditional diagnosis is based mainly on lesion distribution and histologic features, but morphology alone has limitations when lesions share similar histologic types. Comprehensive histologic assessment, thin-section computed tomography, and selective molecular testing provide complementary evidence for differentiating SMPLC from IPM. Surgery remains the principal treatment for resectable SMPLC. The choice among lobectomy, anatomical segmentectomy, wedge resection, and combined resection should consider the invasiveness of the dominant and secondary lesions, the number and distribution of lesions, laterality, nodal status, predicted postoperative pulmonary function, comorbidity, and cumulative loss of lung parenchyma. In carefully selected patients with early-stage disease, parenchyma-sparing strategies may provide acceptable oncologic outcomes; however, current evidence is derived mainly from retrospective studies and is limited by selection bias and heterogeneous diagnostic criteria.

Conclusions: Accurate multidisciplinary diagnosis and individualized surgical planning are central to SMPLC management. Prospective multicenter studies using standardized diagnostic criteria are needed to clarify the optimal extent of resection, timing of bilateral surgery, and management of residual low-risk ground-glass nodules.