Trajectories of Synchronous Subsolid Nodules in Patients With Resected Subsolid Lung Adenocarcinoma: A Multicenter Cohort Study

Multifocal subsolid nodules (SSNs) are increasingly detected with widespread lung cancer screening and advanced thoracic imaging, representing a spectrum of multifocal lung adenocarcinomas (LUADs). When synchronous SSNs coexist with a surgically confirmed subsolid LUAD, their trajectories remain poorly understood, contributing to uncertainty regarding optimal management strategies. This study aimed to evaluate the clinical course and impact of synchronous SSNs in such patients and to identify features associated with their progression. We analyzed the clinical course of synchronous SSNs in individuals who underwent surgical resection for subsolid LUAD between January 2009 and December 2019 at four referral centers in South Korea, with follow-up through June 2024. Longitudinal outcomes, including growth patterns and subsequent lung cancer diagnosis, were evaluated using comprehensive nodule-level assessments. Multivariable Cox regression models were used to identify risk factors associated with SSN trajectories and patient-level mortality outcomes. Overall, 1,791 synchronous SSNs in 409 patients with surgically resected subsolid LUAD as the index lesion were included. During the initial surgery for the 409 index LUADs, 380 synchronous SSNs were resected concurrently, while 1,002 SSNs were followed up over a mean duration of 80.6 months. Among the 1,002 SSNs, 16.9% exhibited growth, and 7.9% were subsequently diagnosed as lung cancer-all of which were stage 0-I adenocarcinomas. Factors associated with SSN growth and lung cancer diagnosis included part-solid type, larger nodule size, presence of bubble lucency, and pleural retraction. Notably, the number of synchronous SSNs was not associated with an increased risk of growth. At the individual patient level, neither the absolute number nor the mere growth of synchronous SSNs significantly impacted lung cancer-related mortality or overall survival. Synchronous SSNs in patients with subsolid LUAD exhibited growth in 16.9% of cases, with varying trajectories and clinical impact. Identified risk factors were primarily related to the characteristics of each SSN. Our findings highlight the need for nodule-based, individualized management strategies, along with a more clinically relevant growth threshold to guide balanced intervention decisions.