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

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Key Points

  • 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. Lung cancer appeared after a median time of 52 months from detection of the subsolid nodule.
  • Lung cancer not originating from the subsolid nodule was seen in 22 of 30 (73%) of patients with subsolid 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.

Subsolid nodules can be considered a biomarker of lung cancer risk, and should be managed with long-term active surveillance. Conservative management of these nodules may reduce unnecessary surgery and overtreatment in patients with multiple comorbidities and aggressive lung cancer arising from lung sites other than the subsolid nodule. These conclusions were published by Silva et al in the Journal of Thoracic Oncology.

Lung cancer screening by low-dose computed tomography (LDCT) allows for early detection and early treatment of lung cancer, thereby reducing lung cancer–related deaths. However, LDCT 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 the subsolid nodule. 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 LDCT 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 (CAD). All subsolid nodules were classified into nonsolid nodules or part-solid nodules and were measured by volumetric semiautomatic segmentation. The volume of the subsolid nodule was measured including the whole nonsolid component (nonsolid nodule and part-solid nodule) and the solid component (part-solid nodule). The risk of overall mortality and lung cancer mortality was tested by Cox proportional hazards model.

Findings

A total of 6,541 nodules were detected in 55.5% (1,277 of 2,303) of the patients screened. Using both visual and CAD screening, 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 (HR) of 6.77 (95% confidence interval [CI] = 3.39–13.54). Lung cancer not originating from the subsolid nodule was seen in 22 of 30 (73%) of patients with subsolid nodules. Lung cancer appeared after a median time of 52 months from detection of the subsolid nodule. The HR 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 the subsolid nodule.

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 nodule] 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 nodule]. We suggest that subjects with [subsolid nodules] might be a suitable target population for pharmacological smoking-cessation and chemoprevention trials.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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