A Decision Analysis of Follow-up and Treatment Algorithms for Nonsolid Pulmonary Nodules

Abstract

onsolid nodules (sometimes known as subsolid nodules), which include ground-glass nodules (GGNs) and part-solid nodules (PSNs), are commonly identified on chest CT images. These are found in approximately 9% of patients undergoing low-dose CT for lung cancer screening (1,2). Although some nonsolid nodules are transient and likely inflammatory (1,2), many of those that persist range from premalignant lesions to invasive adenocarcinomas (3,4). Nonsolid nodules are more likely to represent lung cancer than solid nodules (5) but are also more likely to exhibit indolent behavior (ie, slow growth and low metastatic potential), which has raised the concern of overdiagnosis and overtreatment of these nodules (6,7). A considerable increase in the number of patients diagnosed with these nodules is expected in the near future, as annual lung cancer screening for high-risk individuals has been recommended by both the U.S. Preventive Services Task Force and the Center for Medicare and Medicaid Services (1,2). Hence, there is an urgent need to address the question of how best to manage nonsolid nodules. Studies of nonsolid nodule behavior provide a great deal of information that can be used to inform recommendations for nonsolid nodule management. Results of natural history studies evaluating the growth of nonsolid nodules have shown that most of these lesions grow slowly over the course of years, and some never grow at all (8-10). Furthermore, the discrepancy between low lung cancer diagnosis rates among screened patients (1,2,11) and high diagnosis rates among patients undergoing biopsy (12,13) indicates that many nonsolid nodules that are pathologically diagnosed as malignant after biopsy will never manifest clinically. Recurrence-free survival for nonsolid lung cancers after resection is far better than that for solid lung cancers (14), and study results have shown that ground-glass adenocarcinomas in particular rarely metastasize to lymph nodes (2,15). Finally, because ground-glass adenocarcinomas are indolent, the optimal treatment modality is controversial; it remains an open question whether stereotactic body radiation therapy (SBRT) or percutaneous ablation are adequate substitutes for lobectomy, the standard of care for invasive lung cancers.

Shades of Gray

“…Simulation modeling has suggested superior outcomes with stereotactic body radiation therapy compared with lobectomy or nontherapy for SSNs. 80 However, trials comparing these treatments to establish noninferiority of ablative options have failed to accrue participants. The gold standard remains surgical resection for patients who are surgical candidates.…”

Subsolid pulmonary nodules: Controversy and perspective

“…Given the indolent behavior and low metastatic potential for subsolid adenocarcinomas, the benefits of surgery are likely reduced in these cancers. One simulation-based analysis suggested that radiation therapy may even provide improved outcomes in these patients because of less treatment-related morbidity and mortality [ 35 ]. Future research is needed in this arena to better define the benefits of surgery versus non-surgical management of subsolid malignancies.…”

Cost-Effectiveness of Follow-Up for Subsolid Pulmonary Nodules in High-Risk Patients

“…By simulating a sufficiently large number of patients (N ¼ 10,000,000), we ensured that the results would be stable. Some elements of the model's structure are described here; others are detailed in Supplementary Section 1 and the supplement of Hammer et al 12 We used results from the literature and from secondary data analysis of the NLST data 13 to estimate model parameters, including nodule size, growth rate distributions, and patient characteristics, such as age and smoking status. In addition to modeling malignancy developing from subsolid nodules, we allowed for the development of incidental lung cancers.…”

“…For this analysis, patient-level age-and smoking status-dependent incidental cancer rates were derived using the PLCOm2012 model, 14 with the Smoking History Generator 15,16 used to model individuals' smoking history. The probability of patient death at any given month depends on age, smoking status, presence and stage of clinically significant lung cancer, and whether the patient had received treatment, as detailed in the Supplement, Section 1 and Hammer et al 12…”

“…Based on these conflicting data, some have suggested modifications to the Lung-RADS, such as using more granular risk categorizations 11 or extending the follow-up interval length for low-risk nodules. 12 Nevertheless, to our knowledge, neither existing guidelines nor these modifications have been evaluated for their cost-effectiveness.…”