What is the appropriate workup for a 2.1 cm pulmonary nodule?

From the Guidelines

For a 2.1 cm lung nodule, I recommend prompt referral to a pulmonologist or thoracic surgeon for evaluation and likely biopsy, as this size nodule has a higher risk of malignancy, approximately 50% or higher, as suggested by the Fleischner Society guidelines 1. The workup should include a contrast-enhanced chest CT if not already done, to further characterize the nodule and assess for any potential metastatic disease.

• A PET-CT scan is also typically indicated for nodules of this size to assess for metabolic activity suggestive of cancer, with reported sensitivities and specificities ranging from 88% to 96% and 77% to 88%, respectively 2.
• Complete pulmonary function testing should be performed to assess surgical candidacy if malignancy is confirmed, as surgical resection is both the gold standard for diagnosis and the definitive treatment of a malignant nodule 3.
• The patient should be counseled about smoking cessation if applicable, as continued smoking increases risk of complications from any procedure and worsens outcomes if cancer is diagnosed.
• Time is of essence with nodules of this size, as prompt diagnosis and treatment of lung cancer significantly improves survival outcomes.
• If cancer is diagnosed, molecular testing of the tissue should be performed to guide treatment options, as this can help identify specific genetic mutations that may be targeted with specific therapies.
• The decision to pursue surgical diagnosis must take into account the benefits of definitive diagnosis and treatment when compared with the surgical risk, with video-assisted thoracic surgery (VATS) being the strongly preferred diagnostic approach for nodules 3.

From the Research

Diagnostic Approaches for 2.1 cm Lung Nodule

• The diagnosis of a 2.1 cm lung nodule can be approached through various methods, including bronchoscopy, positron emission tomography (PET) scanning, computed tomography (CT)-guided biopsy, and transbronchial biopsy with endobronchial ultrasound [ 4, 5, 6 ].
• A study published in 2005 found that combining bronchoscopy and PET scanning has a useful role in the diagnosis of noncalcified chest radiologic lesions ≤ 3 cm in size [ 4 ].
• For sub-centimetre lung nodules, CT-guided biopsy has been shown to be a safe and highly accurate diagnostic method [ 5 ].

Comparison of Diagnostic Methods

• A meta-analysis of randomized controlled trials compared the diagnostic and safety profiles of CT-guided transthoracic biopsy and transbronchial biopsy with endobronchial ultrasound and flexible bronchoscope for solitary lung nodules [ 6 ].
• The results showed that CT-guided biopsy had a higher diagnostic yield than transbronchial biopsy, especially for lesions 1-2 cm in size [ 6 ].
• However, transbronchial biopsy had a significantly better safety profile with lower risks of pneumothorax and combined outcomes of hospital admission, hemorrhage, and pneumothorax [ 6 ].

Cost-Effectiveness and Radiation Dose

• A cost-consequences analysis compared the costs and consequences of navigational bronchoscopy with biopsy versus CT-guided biopsy for the diagnosis of a solitary pulmonary nodule [ 7 ].
• The results showed that navigational bronchoscopy increased average costs by $3719 per case and increased VATS rates by an absolute 20% [ 7 ].
• A study published in 2021 found that an ultra-low-dose CT-guided lung biopsy protocol yielded a reduction in radiation dose without significant change in accuracy, image quality, and complication rate [ 8 ].