Advancements in localization of peripheral pulmonary nodules for diagnosis and treatment

Jan. 22, 2016

Lung cancer remains one of the leading causes of cancer-related mortality and morbidity. In the year 2015, it was estimated that 221,200 new cases of lung cancer would be diagnosed in the United States and 158,040 patients would die of lung cancer. Non-small cell lung cancer accounts for approximately 85 percent of lung cancer diagnoses and carries an overall five-year survival rate of 17.4 percent.

Effective implementation of lung cancer screening, as is currently done at Mayo Clinic using low-dose computerized tomography (LDCT) of the chest, is expected to improve associated mortality and morbidity, with a demonstrated 20 percent relative reduction in mortality shown in the National Lung Screening Trial (NLST).

Based on the NLST result, the U.S. Preventive Services Task Force, as well as many professional societies, recommends annual screening for lung cancer with LDCT in adults ages 55 to 80 years who have a 30 pack-a-year smoking history and currently smoke or have quit within the past 15 years.

Of screening-detected nodules, however, less than 4 percent will prove to be malignant with the remaining 96 percent requiring serial follow-up, invasive diagnostic maneuvers or both. With that the ability to safely and effectively sample, diagnose and potentially treat screening-detected abnormalities takes on additional importance, and has become a major focus of investigation and innovation in interventional pulmonary medicine and thoracic surgery.

Lung tumors, depending on their location in the tracheobronchial tree, are categorized as central or peripheral. Central tumors, according to American College of Chest Physician (ACCP) guidelines, are sampled easily under direct bronchoscopic visualization with an 88 percent diagnostic yield. Early-stage lung cancer, however, frequently presents as a peripheral pulmonary nodule and is often curable by surgical resection.

ACCP guidelines for establishing the diagnosis of lung cancer report the diagnostic yield of bronchoscopy decreases from 63 percent to 34 percent when the peripheral pulmonary nodule is smaller than 2 centimeters, creating a particular challenge for bronchoscopists in establishing a diagnosis in smaller lesions using traditional bronchoscopic techniques.

In the NLST, the vast majority of screening-detected nodules were less than 10 millimeters in size, with almost two-thirds less than 7 millimeters. Radial endobronchial ultrasound and navigation bronchoscopy are emerging technologies especially well-suited for the diagnosis of small peripheral nodules, demonstrating a diagnostic yield of 73 percent and 71 percent, respectively.

This compares with the pooled sensitivity of transthoracic needle aspiration (TTNA) of 90 percent, but TTNA also trends toward lower sensitivity for nodules less than 2 centimeters in diameter at a higher complication rate than bronchoscopically sampled nodules. A complication rate of up to 30 percent is noted for TTNA compared with a complication rate of 2 percent for navigation bronchoscopy.

Localization and management of small pulmonary nodules

PET scan showing nodule

Electromagnetic navigation

CT confirmation of guide position

Methylene blue marker on the lung's surface

Complete resection of the lesion

Mayo Clinic bronchoscopists routinely use a combination of specialized bronchoscopes, electromagnetic navigation, endobronchial ultrasound localization and rapid on-site histopathologic diagnosis in their assessment of suspicious peripheral lung nodules.

More recently, Mayo has incorporated the use of real-time chest computerized tomography (CT) to further aid in nodule localization. This, in concert with electromagnetic navigation, which provides a 3-D road map of the lungs and real-time information about the position of a steerable probe during bronchoscopy, further optimizes diagnostic yield and facilitates dye and fiducial marker placement to direct surgical and radiotherapy treatment options.

This continued collaboration between interventional pulmonology, radiation oncology and thoracic surgery specialists has resulted in successful localization and management of pulmonary nodules smaller than 1 centimeter. At times when it may be difficult for a thoracic surgeon to localize and feel a ground-glass or soft nodule, especially in patients with underlying lung disease, dye placement by interventional pulmonary specialists using methylene blue just before surgery has resulted in successful resection and a decrease in operative time.

Going forward, these localization and diagnostic tools and techniques offer the promise of less invasive treatments of lung cancer in patients who are deemed poor surgical candidates. In high-risk surgical patients, bronchoscopic localization and confirmation of lung cancer may allow opportunities to perform nonsurgical tumor treatment using cryoablation or microwave ablation.

Studies using novel ablative devices

Safety and Efficacy of Cryoablation for Metastatic Lung Tumors (ECLIPSE), a recent multicenter study including Mayo Clinic, describes the successful use of percutaneous CT-guided cryoablation in local treatment of up to five metastatic lesions, each less than 3.5 centimeters in diameter. This technique was shown to be effective in treating various types of metastases with up to a 96 percent local control rate at 12 months.

A larger multicenter study involving Mayo Clinic and Gustave Roussy, Paris, called the Study of Cryoablation for Metastatic Lung Tumors (SOLSTICE), is currently enrolling patients, as is The Emprint Ablate and Resect Study in Patients With Metastatic Lung Tumors (EMPRESS), a multicenter study investigating the percutaneous use of the Emprint microwave ablation system to treat metastatic and primary lung tumors. Likewise, several manufacturers are investigating the use of bronchoscopically deployed ablative devices, which, if successful, will further limit the risks posed by the percutaneous approach.

In the meantime, Mayo Clinic investigators are actively engaged in the testing of various percutaneous ablative devices using both cold and thermal energy sources, and a multidisciplinary lung ablation committee meets regularly to review cases for potential ablative therapies.

To learn more about current studies using novel ablative devices, or to have a case reviewed at the lung ablation meeting, contact Shanda Blackmon, M.D., M.P.H., Thoracic Surgery, at

For additional information about the Mayo Clinic Lung Cancer Screening Program, contact David E. Midthun, M.D., Pulmonary and Critical Care Medicine, at

For more information

Mass one month after ablation

Mass six months after ablation

Mass prior to cryoablation

Detterbeck FC, et al. Screening for lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(suppl):e78s.

Galil Medical. Safety and Efficacy of Cryoablation for Metastatic Lung Tumors (ECLIPSE).

Galil Medical. Study of Cryoablation for Metastatic Lung Tumors (SOLSTICE).

Medtronic - MITG. The Emprint Ablate and Resect Study in Patients With Metastatic Lung Tumors (EMPRESS).