Adenocarcinoma of the Lung: Definition, Staging, and Treatment
Adenocarcinoma of the lung is the most common type of non-small cell lung cancer (NSCLC), accounting for approximately 40-50% of all lung cancer cases, and requires stage-specific treatment approaches including surgery, radiation, chemotherapy, targeted therapy, and immunotherapy based on molecular characteristics and extent of disease. 1
Definition and Characteristics
- Adenocarcinoma is a subtype of NSCLC that accounts for approximately 40-50% of all lung cancer cases 1
- It occurs more frequently in women and has a higher prevalence in non-smokers compared to other lung cancer types 1
- Adenocarcinomas are usually thyroid transcription factor-1 (TTF-1) positive, which helps distinguish them from squamous cell carcinomas 1
- The WHO classification for adenocarcinoma includes several categories:
- Adenocarcinoma in situ (AIS): a preinvasive lesion (formerly bronchioloalveolar carcinoma) 1
- Minimally invasive adenocarcinoma (MIA): predominant lepidic growth with ≤5 mm invasion 2
- Invasive adenocarcinoma: includes several patterns (lepidic, acinar, papillary, solid, micropapillary) 2
- Variants include invasive mucinous adenocarcinoma, colloid, fetal, and enteric adenocarcinoma 2
Staging of Lung Adenocarcinoma
Lung cancer staging follows the TNM (Tumor, Node, Metastasis) classification system according to the American Joint Committee on Cancer (AJCC) 7th edition 1:
T (Primary Tumor) Classification:
- T0: No evidence of primary tumor 1
- Tis: Carcinoma in situ 1
- T1: Tumors ≤3 cm in greatest dimension
- T2: Tumors >3 cm to 5 cm or involving visceral pleura, main bronchus, or causing atelectasis 1
- T3: Tumors >5 cm to 7 cm or invading chest wall, phrenic nerve, parietal pleura, or pericardium; or separate tumor nodules in the same lobe 1
- T4: Tumors >7 cm or invading mediastinal structures, diaphragm, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina 1
N (Regional Lymph Node) Classification:
- N0: No regional lymph node metastasis
- N1: Metastasis in ipsilateral peribronchial and/or hilar lymph nodes
- N2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes
- N3: Metastasis in contralateral mediastinal, contralateral hilar, or supraclavicular lymph nodes
M (Distant Metastasis) Classification:
- M0: No distant metastasis
- M1a: Separate tumor nodule(s) in a contralateral lobe; pleural or pericardial nodules or malignant pleural or pericardial effusion 1
- M1b: Single extrathoracic metastasis
- M1c: Multiple extrathoracic metastases in one or more organs
Stage Grouping:
- Stage I: Early, localized disease (T1-2, N0, M0)
- Stage II: Locally advanced disease (T1-3, N0-1, M0)
- Stage III: Locally advanced disease (T1-4, N1-3, M0)
- Stage IV: Metastatic disease (Any T, Any N, M1)
Treatment by Stage
Stage I (Localized Disease)
- Primary treatment: Surgical resection (lobectomy with systematic lymph node dissection) 1
- For radio-occult cancer: If CT scan shows no nodal invasion, local treatments may be considered for small lesions 1
- Adjuvant therapy: For stage IB (T2a ≥4 cm), adjuvant chemotherapy may be considered 3
- For patients unfit for surgery: Stereotactic body radiation therapy (SBRT)
Stage II (Locally Advanced)
- Primary treatment: Surgical resection (lobectomy or pneumonectomy with systematic lymph node dissection) 1
- Adjuvant therapy: Platinum-based chemotherapy is recommended following complete resection 3
- For adenosquamous carcinoma: More aggressive treatment approach is needed as this variant shows worse prognosis than pure adenocarcinoma 4
Stage III (Locally Advanced)
- For resectable disease: Multimodality approach with surgery followed by adjuvant chemotherapy
- For unresectable disease: Concurrent chemoradiation therapy
- For stage IIIA with N2 disease: Neoadjuvant chemotherapy followed by surgery may be considered
- For stage IIIB: Definitive concurrent chemoradiation therapy 1
- Consolidation immunotherapy: Following chemoradiation for unresectable stage III disease
Stage IV (Metastatic Disease)
- Molecular testing: All patients with adenocarcinoma should be tested for EGFR mutations and ALK gene rearrangements 1
- For EGFR mutation-positive: EGFR tyrosine kinase inhibitors (TKIs) like erlotinib as first-line therapy 3
- For ALK-positive: ALK inhibitors like crizotinib as first-line therapy 1
- For PD-L1 expression ≥1%: Pembrolizumab as first-line therapy for patients without EGFR or ALK aberrations 5
- For non-squamous histology without driver mutations: Combination chemotherapy with platinum-based regimens plus pemetrexed 5
- Maintenance therapy: Consider for patients with good performance status after first-line therapy 3
Special Considerations
- Multifocal lung adenocarcinoma with ground-glass features: These are typically considered separate primary lung cancers with better prognosis and less lymph node involvement 1
- Pneumonic-type adenocarcinoma: Usually corresponds to invasive mucinous adenocarcinoma with worse prognosis than multifocal adenocarcinoma with ground-glass features 1
- Multiple pulmonary nodules: Determining whether these represent separate primary tumors or intrapulmonary metastases is critical for staging and treatment planning 1
- Molecular profiling: Comprehensive molecular testing is essential for personalized treatment selection, particularly for advanced disease 1
Prognosis
- 5-year survival rates vary significantly by stage:
- Good prognostic factors include early-stage disease, good performance status, minimal weight loss, and female sex 1
- Patients with AIS or MIA who undergo complete resection have nearly 100% disease-specific survival 2
The management of lung adenocarcinoma has evolved significantly with advances in molecular diagnostics and targeted therapies, making accurate histological classification and molecular testing essential components of the diagnostic workup for optimal treatment selection.