Natural History, Treatment, Survival, and Causes of Mortality in Patients With Subsolid and Ground-Glass Nodules

Subsolid nodules (SSNs) and ground-glass opacities (GGOs) are an increasingly common clinical problem. This unique subtype of lung adenocarcinoma poses a treatment dilemma because many can be safely monitored with radiographic observation alone and require no intervention. Improved understanding of the natural history and outcomes of patients with SSNs is needed to improve clinical decision-making and treatment recommendations.

What is the natural history of growth, likelihood of treatment, and most likely cause of mortality in a comprehensive cohort of patients with SSNs and GGOs identified on chest CT scan?

Natural language processing was used to identify all patients with SSNs on outpatient chest CT scans in 2017 (n = 17,276) in the Yale New Haven Health System. Manual chart review was performed for demographics, nodule size, growth on subsequent CT scan, treatment, pathology, and survival.

A cohort of 322 patients were identified with 64% (n = 207) nonsolid nodules (pure GGO) and 36% (n = 115) part-solid nodules. Over 5 years of follow-up, 81% of nonsolid nodules remained nonsolid and 19% developed a new solid component. Within 5 years, 19% (n = 60) underwent treatment, with patients with part-solid nodules being more likely to undergo treatment than those with nonsolid nodules (32% vs 11%, respectively; P < .001). Five-year overall survival was 79.8%, with 98.4% 5-year SSN-related survival. Development of a new, second primary malignancy was common in patients with SSN, who were significantly more likely to die from a secondary primary cancer than their SSN at 5 years (8.43% vs 1.54%, respectively; P < .001).

Patients should be reassured regarding the excellent survival associated with SSNs. Our results indicate that most can be safely observed without intervention, particularly nonsolid nodules or pure GGOs. Patients with SSNs were shown to have high rates of developing multiple lung nodules and second primary lung cancer.