What is the management approach for a patient with multifocal ground glass opacities?

Management of Multifocal Ground Glass Opacities

For patients with multifocal ground glass opacities (GGOs) suspected to represent multifocal lung cancer, pursue curative-intent treatment with sublobar resection of all lesions suspected of being malignant, if feasible, rather than treating as advanced metastatic disease. 1

Initial Diagnostic Approach

Determine if Lesions Represent Multifocal Lung Cancer (MFLC)

• Define MFLC clinically as multiple lesions arising from GGOs, which may develop a solid component, rather than relying on pathologic features that are unavailable until after resection 1
• Include patients with a dominant GGO lesion suspected or proven malignant plus other small GGO lesions that may represent adenomatous alveolar hyperplasia (AAH), as AAH is a precursor to invasive adenocarcinoma 1
• Distinguish from metastatic disease: These lesions should NOT be classified as T4 or M1a disease, as they represent synchronous primary tumors with excellent prognosis, not intrapulmonary metastases 2

Staging Evaluation

• For patients with negative clinical evaluation and normal mediastinum by CT, distant and mediastinal staging are NOT routinely necessary (Grade 2C recommendation) 1
• This differs from typical lung cancer staging because multifocal GGO lesions have decreased propensity for nodal and systemic metastases 1
• Measure the solid component of part-solid tumors using lung or intermediate window settings to assign T category, while recording the whole tumor size 1

Surgical Management Strategy

Primary Treatment Approach

• Perform anatomic resection (lobectomy or segmentectomy) of the dominant tumor combined with wedge resection of accessible ipsilateral GGOs 2
• Sublobar resection is preferred for all lesions suspected of being malignant to preserve lung parenchyma, given the increased propensity to develop new pulmonary foci and need for future interventions 1
• For tumors <2 cm with pure ground-glass opacity, atypical resection is initially recommended, with definitive management determined by final pathology 1

Rationale for Aggressive Curative-Intent Approach

• Survival of 100% and very low recurrence rates have been reported after resection of MFLC 1
• This excellent survival argues for curative-intent rather than palliative treatment 1
• Patients should NOT be considered to harbor advanced disease despite multiple lesions 2

Management of Unresected GGO Lesions

Observation Strategy ("Whack-a-Mole" Approach)

• Small GGO lesions ≤10 mm that are pure ground glass (likely AAH) should be observed rather than resected 1
• These lesions should be approached according to data for isolated lesions with the same characteristics 1
• Only 23% of unresected nodules increase in size during follow-up, with mean doubling time of 49 months 2

Follow-Up Protocol

• New GGOs develop in 41% of patients but typically remain ≤7 mm and require no immediate intervention 2
• CT follow-up for pure non-solid lesions does not need shorter intervals than 1-2 years, as these are less aggressive than solid or part-solid lesions 1
• Intervene surgically when lesions become sufficiently suspicious of being malignant (developing solid component, increasing size) 1, 3

Adjuvant Therapy Considerations

• Adjuvant chemotherapy or radiotherapy is NOT recommended for pN0 multifocal cancer, as the propensity for nodal and distant metastases is low 1
• Consider adjuvant therapy only if N1 or N2 involvement is found at surgery, following standard NSCLC guidelines 1

Alternative Approaches for Selected Patients

For Patients Unable to Tolerate Multiple Resections

• Electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation combined with video-assisted thoracoscopic surgery is safe and feasible, with 100% success rate and no local recurrence in small series 4
• This represents an alternative for patients who cannot tolerate simultaneous resection of multiple tumors 4

Diagnostic Workup for Indeterminate Lesions

• Stepwise approach: oral antibiotics, follow-up HRCT at 40-60 days, then CT-guided core biopsy if lesion persists 5
• This increases diagnostic specificity and reduces time to definitive diagnosis 5
• Transthoracic puncture has excellent sensitivity but carries ~20% risk of pneumothorax 1

Critical Pitfalls to Avoid

• Do not treat multifocal GGOs as stage IV metastatic disease - these patients have 100% survival with appropriate surgical management and should receive curative-intent treatment 1, 2
• Do not perform extensive mediastinal staging in patients with negative clinical evaluation and normal mediastinum on CT - this is unnecessary and delays appropriate treatment 1
• Do not resect all GGO lesions simultaneously - preserve lung parenchyma by observing small pure GGOs and intervening only when they demonstrate concerning features 1, 3
• Do not use PET for screening or initial evaluation - PET has only 81% negative predictive value for GGO lesions and is insufficient to conclude benignity 1