HemeOnc

Non-Small Cell Lung Cancer

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Non-Small Cell Lung Cancer, Non-Small Cell Adenocarcinoma, Squamous Cell Lung Cancer, Lung Adenocarcinoma, Large Cell Lung Cancer

  • See Also
  1. Lung Cancer
  • Epidemiology
  1. Lung Cancer mortality dwarfs other causes of cancer death for the last 50 years
  • Types Non-Small Cell Lung Cancer (75% of Lung Cancers)
  1. Squamous Cell Carcinoma (25%)
    1. Late metastases
    2. Central endobronchial lesions
    3. Presents with Hemoptysis, Pneumonia, Atelectasis
  2. Adenocarcinoma (40%)
    1. Peripheral lesions
    2. Early metastases
    3. Associated with underlying lung disease
    4. Types
      1. Acinar
      2. Bronchioalveolar
      3. Papillary
      4. Solid carcinoma with mucus formation
  3. Large cell carcinoma (10%)
    1. Poorly differentiated tumors
    2. Large peripheral lesions
    3. Types
      1. Neuroendocrine type
      2. Basaloid type
      3. Lymphoepithelial-like
      4. Rhabdoid Phenotype
  4. Other uncommon Lung Cancers (<5 of Lung Cancers)
    1. Adenosquamous carcinoma
    2. Carcinoid
    3. Bronchial gland carcinoma
  • Evaluation
  • Resectable Disease
  1. Surgical Lymph Node evaluation is critical
  2. Step 1: General testing
    1. Complete History and Physical
    2. Pathology review
    3. CT chest and Abdomen
    4. Complete Blood Count
    5. Chemistry panel
    6. Tobacco Cessation
  3. Step 2: Stage Peripheral T1-2NO or Central T1-2N0
    1. Step 1 testing and
    2. Pulmonary Function Tests
    3. Bronchoscopy
    4. Mediastinoscopy
    5. PET Scan
  4. Step 3: Stage T1-2N1 or T1-3N2
    1. Step 2 testing and
    2. Brain MRI (for stage 2B, MRI only if non-squamous cell cancer)
  5. Step 4: Stage T1-2N1 or T1-3N2
    1. Step 3 testing and
    2. Spine MRI and thoracic inlet MRI
  • Staging
  1. Resources
    1. Staging Calculator
      1. http://staginglungcancer.org/calculator
  2. Stage IA: Local (T1N0M0)
    1. Characteristics
      1. Primary tumor <3 cm
      2. No nodal involvement
      3. No distant metastases
    2. Prognosis
      1. Surgical cure rate: 80%
  3. Stage IB: Local (T2N0M0)
    1. Characteristics
      1. Primary tumor >3 cm
      2. No nodal involvement
      3. No distant metastases
    2. Prognosis
      1. Surgical cure rate: 60%
  4. Stage II: Locally advanced (T2N1M0, T3N0M0)
    1. Characteristics
      1. Primary tumor any size and confined to the lung
      2. Ipsilateral Bronchial or hilar node involvement
      3. No distant metastases
    2. Prognosis
      1. Surgical cure rate: 30 to 40%
  5. Stage IIIA: Locally advanced (T1N2M0, T2N2M0, T3N1-2M0)
    1. Characteristics
      1. Ipsilateral mediastinal Lymph Node involvement or
      2. Primary tumor with local extension
        1. Extension to pleura or chest wall or
        2. Extension to Pericardium or
        3. Extension to diaphragm or
        4. Extension to within 2 cm of carina
    2. Prognosis
      1. Surgical cure rate: 10 to 20%
  6. Stage IIIB: Advanced (T4N1-3M0)
    1. Characteristics
      1. Contralateral Lymph Node involvement or
      2. Primary tumor with local invasion
        1. Tumor invasion of mediastinum
        2. Malignant Pleural Effusion
    2. Prognosis
      1. Surgical cure rate: <5%
  7. Stage IV: Advanced (T1-4N1-3M1)
    1. Characteristics: Distant Metastases
    2. Prognosis
      1. Surgical cure rate: <5%
  • Management
  • Approach by Stage
  1. Stage I
    1. Surgical resection
  2. Stage II
    1. Surgical resection and Adjuvant Chemotherapy
  3. Stage III
    1. Eradicate intrathoracic cancer
    2. Limit subsequent metastases with Chemotherapy and radiation
  4. Stage IV or low functional status
    1. Multidisciplinary management tailored to pathology and patient functional status
    2. Palliative Care (initiate early for optimal effects on quality of life)
  • Management
  • Approach for Metastases
  1. Brain Metastases
    1. Brain metastases <3 lesions
      1. Stereotactic Radiotherapy with or without surgical resection
    2. Brain metastases >=3 lesions
      1. Whole brain radiation
  2. Bone Metastases
    1. Radiotherapy and Bisphosphonates to reduce pain and Fracture risk
  • Management
  • Surgical Resection
  1. Most effective Non-Small Cell Lung Cancer management
  2. Long-term Cancer Survivorship associated with resection
  3. Recurrence rate following resection: 50%
  4. Indicated in only 30% of patients (I, II, IIIA)
    1. See evaluation above
    2. No significant distant metastases
    3. Locally resectable disease within the chest
  1. Standard of care for resected stage II-IIIA Non-Small Cell Lung Cancer if medically stable
  2. Cisplatin-based regimen for 12 weeks
  • Management
  • Post-operative radiation (PORT)
  1. Indicated for residual disease following resection
  2. Post-operative radiation follows adjuvant Chemotherapy
  1. Indications for genetic and Immunotherapy testing
    1. Nonsquamous NSCLC or mixed histology
    2. Small volume biopsy
  2. Markers
    1. PD-L1 (Programmed Death Ligand 1)
      1. Most important Tumor Marker in NSCLC
      2. Expression percentage (0 to 50) directs Immunotherapy strategy
    2. Genetic Mutations
      1. Anaplastic Lymphoma kinase
      2. BRAF V600E
      3. Epidermal Growth Factor Receptor
      4. MET ex 14 Skipping
      5. NTRK gene fusion
      6. RET
      7. ROS1
  3. Immunotherapy Agents used in NSCLC (Partial List as of 2022, many others are used for genetic mutations)
    1. Pembrolizumab (Keytruda)
    2. Pemetrexed (Alimta)
    3. Atezolizumab (Tecentriq)
    4. Bevacizumab (Avastin)
    5. Cemiplimab (Libtayo)
    6. Nivolumab (Opdivo)
    7. Ipilimumab (Yervoy)
    8. Topotecan (Hycamtin)
    9. Lurbinectedin (Zepzelca)
  • Management
  • Follow-up surveillance
  1. Routine physical examination every 4-6 months for 2 years and then annually
  2. Chest CT
    1. Spiral contrast- enhanced CT every 4-6 months for 2 years, then
    2. Noncontrast-enhanced CT annually thereafter (controversial)
  • Prognosis
  1. Five Year Survival (2017)
    1. Localized NSCLC: 59%
    2. Distant Metastases: 5.8%
  • Prevention
  1. See Lung Cancer
  2. Tobacco Cessation is critical
  • References
  1. Kim (2022) Am Fam Physician 105(5): 487-94 [PubMed]
  2. Hainsworth (1997) Am Fam Physician 55(6):2265-72 [PubMed]
  3. Latimer (2015) Am Fam Physician 91(4): 250-6 [PubMed]
  4. Mountain (1986) Chest 89(4 suppl):223S-33S [PubMed]