Active Surveillance of Lung Subsolid Nodules May Reduce Unnecessary Surgery and Overtreatment

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Subsolid nodules can be considered a biomarker of lung cancer risk and should be managed with long-term active surveillance. Conservative management of subsolid nodules may reduce unnecessary surgery and overtreatment in patients with multiple comorbidities and aggressive lung cancer arising from lung sites other than the subsolid nodules. These conclusions are from a report published by Mario Silva, MD, PhD, of the Università di Parma, and colleagues in theJournal of Thoracic Oncology.1

Mario Silva, MD, PhD

Mario Silva, MD, PhD

Lung cancer screening by low-dose computed tomography (CT) allows for early detection and early treatment of lung cancer, thereby reducing lung cancer–related deaths. However, low-dose CT does have its limitations, such as finding abnormalities that are noncancerous, requiring the patient to have additional testing, and diagnosing and treating malignancies that would have not affected the patient’s life expectancy. Overdiagnosis and overtreatment are often seen in slow-growing lung adenocarcinomas represented by subsolid nodules. Unfortunately, the resection of subsolid nodules might not be clinically advantageous and may result in cardiopulmonary damage in patients with multiple comorbidities. Therefore, treatment by resection vs surveillance for persistent subsolid nodules remains controversial.

Analysis Design

A group of European investigators evaluated the risk of lung cancer and lung cancer–related death in patients with unresected subsolid nodules over a period of almost 10 years and analyzed whether cancer arose from these nodules. The aim was to determine the long-term outcome of patients with unresected subsolid nodules in lung cancer screening. In 2005, the Multicenter Italian Lung Detection (MILD) screening trial implemented active surveillance for persistent subsolid nodules as opposed to early resection. The results of this study were based on the 2,303 patients randomized to the low-dose CT arm (age 58.1 ± 5.9 years, cumulative tobacco exposure 43.6 ± 21.5 pack-years) of the MILD screening trial. Patients with subsolid nodules were selected by visual analysis and computer-aided diagnosis. All subsolid nodules were classified into nonsolid or part-solid nodules and were measured by volumetric semiautomatic segmentation. The volume of subsolid nodules was measured including the whole nonsolid component (nonsolid and part-solid nodules) and the solid component (part-solid nodules). The risk of overall mortality and lung cancer mortality was tested by a Cox proportional hazards model.

Key Findings

A total of 6,541 nodules were detected in 55.5% (1,277 of 2,303) of the patients screened. Using both visual analysis and screening by computer-aided diagnosis, 16.9% of patients (389 of 2,303) were found to have a subsolid nodule. Thirty lung cancers were diagnosed in 389 patients with subsolid nodules, reflecting a 7.7% overall risk of being diagnosed with lung cancer throughout the 9.3 ± 1.2 years of follow-up and hazard ratio of 6.77 (95% confidence interval [CI] = 3.39–13.54). Lung cancer not originating from the subsolid nodule was


Lung subsolid nodules include pulmonary nodules that are morphologically described as pure ground-glass nodules (which show increased lung density or attentuation that does not obscure underlying structures) and part-solid nodules (soft-tissue attenuation within areas of ground-glass attenuation).

seen in 22 of 30 patients (73%) with subsolid nodules. Lung cancer appeared after a median time of 52 months from detection of the subsolid nodules. The hazard ratio for lung cancer–specific mortality was 3.80 (95% CI = 1.24–11.65) for patients with subsolid nodules compared to patients without lung nodules. Lung cancer arising from subsolid nodules did not lead to death within the follow-up period in 100% of patients with subsolid nodule–derived lung cancer compared to 63.6% for lung cancers not derived from subsolid nodules.

The authors commented:

In conclusion, the majority of subjects with [subsolid nodules] who were diagnosed with lung cancer in the MILD cohort had developed a cancer elsewhere in the lungs. Lung cancers that arose from the [subsolid nodules] never represented the cause of death within the nearly 10-year follow-up period. Therefore, [subsolid nodules] can be considered a biomarker of cancer risk, and should be managed by active surveillance until signs of growth of the solid component. This approach will reduce unnecessary surgery with cardiopulmonary damage in subjects with multiple comorbidities, including more aggressive lung cancers arising from lung sites other than the [subsolid nodules]. We suggest that subjects with [subsolid nodules] might be a suitable target population for pharmacological smoking-cessation and chemoprevention trials.” ■

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1. Silva M, Prokop M, Jacobs C, et al: Long-term active surveillance of screening detected subsolid nodules is a safe strategy to reduce overtreatment. J Thorac Oncol. July 3, 2018 (early release online).