Can slowly enlarging ground-glass (computed tomography) nodules be observed without a biopsy?

Management of Slowly Enlarging Ground-Glass Nodules

Slowly enlarging ground-glass nodules can be safely observed without biopsy through structured CT surveillance, as these typically represent indolent lesions with excellent prognosis even when malignant. 1

Classification and Initial Approach

Ground-glass nodules (GGNs) are categorized based on their appearance on CT:

• Pure ground-glass nodules (pGGNs): Hazy opacity with no solid component
• Part-solid nodules: Ground-glass opacity containing a solid component

Size-Based Management Algorithm

Pure Ground-Glass Nodules:

• < 6 mm: No routine follow-up needed 1
  • Exception: High-risk patients with suspicious morphology may benefit from selective follow-up
• 6-8 mm: Follow-up CT at 6-12 months, then every 2 years for 5 years 1
• 8-15 mm: Reassessment at 3 months, then:
  • If growing: Multidisciplinary team (MDT) assessment 1
  • If stable: Annual surveillance for at least 3 years 1
• ≥ 15 mm: Repeat assessment after 1 month (with/without anti-inflammatory therapy) 1
  • If completely resolved: Annual screening
  • If partially resolved: Repeat CT after 3 months
  • If persistent: MDT evaluation

Part-Solid Nodules:

• < 6 mm: Annual screening 1
• 6-8 mm: CT surveillance at 3,12, and 24 months, then annually for 1-3 years 1
• > 8 mm: Repeat CT at 3 months, then consider PET, biopsy, or surgical resection if persistent 1

Evidence Supporting Observation

The 2017 Fleischner Society guidelines provide strong evidence supporting observation of slowly growing GGNs 1:

1. Indolent Nature: Pure ground-glass nodules typically grow very slowly, with an average of 3-4 years required to establish growth or develop invasive characteristics 1

2. Excellent Prognosis: Even when malignant, these lesions have excellent outcomes. In a large screening study of 2,392 pure ground-glass nodules, 73 proved to be adenocarcinomas with 100% survival rate 1

3. Slow Growth Rate: Doubling times for malignant subsolid nodules range from 400-1,500 days, making frequent short-term follow-up unnecessary 1

4. Low Progression Rate: The MILD trial showed extremely low progression rates toward clinically relevant disease, with only 16.7% of pure GGNs showing progression over 50 months 2

When to Consider Intervention

Certain features warrant closer monitoring or intervention:

1. Development of a solid component: This often indicates progression to invasive adenocarcinoma 1

2. Significant growth: Increasing size, especially diameter >10mm 1

3. Suspicious morphology: Presence of bubbly lucencies 1

4. High-risk patient factors: History of lung cancer, significant smoking history, or other risk factors 1

Pitfalls and Caveats

1. Measurement challenges: Subtle changes in GGNs can be difficult to detect. Use thin-section (1mm) CT images for accurate assessment 1

2. Overdiagnosis risk: Some GGNs may represent indolent cancers that would never become clinically significant during a patient's lifetime 1

3. Variable reader agreement: Both interreader and intrareader agreement for detection of a solid component in GGNs is only modest 1

4. Limited PET utility: PET has poor sensitivity for pure ground-glass nodules with a negative predictive value of only 81% 1

5. Biopsy limitations: For pure ground-glass nodules, diagnosis often cannot be confirmed by biopsy 1, and surgical resection without prior tissue diagnosis may be appropriate for highly suspicious nodules 3

By following a structured surveillance approach based on nodule size and characteristics, most slowly enlarging ground-glass nodules can be safely monitored without immediate biopsy, reducing unnecessary procedures while maintaining excellent clinical outcomes.