What is the initial treatment approach for a patient diagnosed with adenocarcinoma (a type of non-small cell lung cancer) of the lung?

Initial Treatment Approach for Adenocarcinoma of the Lung

For patients with adenocarcinoma of the lung, the initial treatment approach should be based on accurate staging, molecular testing, and patient-specific factors, with platinum-based combination chemotherapy being the standard first-line treatment for metastatic disease without actionable mutations. 1

Diagnosis and Staging

• Adequate tissue sampling is essential for histological diagnosis and molecular testing to guide treatment decisions 1

• Pathological diagnosis should be made according to the WHO classification, with specific subtyping of all NSCLCs necessary for therapeutic decision-making 1

• Initial evaluation should include:

  • Complete history including smoking history, weight loss, performance status, and physical examination 1
  • Contrast-enhanced CT scan of the chest and upper abdomen 1
  • Brain imaging (preferably MRI) in patients eligible for loco-regional treatment 1
  • PET-CT scan for mediastinal lymph nodes and distant metastasis assessment 1

• Invasive mediastinal staging is recommended for patients with:

  • Radiographically normal mediastinum (by CT and PET) and a central tumor or N1 lymph node enlargement 1
  • A needle technique (EBUS-NA, EUS-NA or combined EBUS/EUS-NA) is suggested as the first test over surgical staging 1

• For peripheral clinical stage IA tumors (negative nodal involvement by CT and PET), invasive pre-operative evaluation of mediastinal nodes is not required 1

Molecular Testing

• EGFR mutation status should be systematically analyzed in advanced NSCLC with non-squamous histology 1
• ALK rearrangement testing should be performed in advanced non-squamous NSCLC 1
• Testing may focus on never/former light smokers especially in the absence of an activating EGFR mutation or KRAS mutation 1
• Sufficient tissue should be obtained to allow for molecular testing, which guides treatment decisions 1

Treatment Based on Stage

Early Stage Disease (Stages I-II)

• Surgical resection is preferred for stages I through IIIA non-small cell carcinoma 1
• For patients with completely resected Stage IB (T2a ≥4 cm), II, or IIIA NSCLC, adjuvant treatment with nivolumab as a single agent may be considered after platinum-based chemotherapy 2

Locally Advanced Disease (Stage III)

• A multimodality approach may include surgery, radiotherapy, and chemotherapy 1
• For patients with resectable (tumors ≥4 cm or node positive) NSCLC, neoadjuvant treatment with nivolumab in combination with platinum-doublet chemotherapy is an option 2

Metastatic Disease (Stage IV)

• Platinum-based combination chemotherapy is the standard first-line treatment for patients with good performance status 1
• For non-squamous histology, pemetrexed is preferred to gemcitabine according to survival benefit 1
• For patients with PD-L1 expression (TPS ≥1%) and no EGFR or ALK genomic tumor aberrations:
  • Pembrolizumab as a single agent is indicated for first-line treatment 3
  • Nivolumab in combination with ipilimumab is indicated for first-line treatment 2
• For patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations:
  • Pembrolizumab in combination with pemetrexed and platinum chemotherapy is indicated as first-line treatment 3

Special Considerations

• In the case of solitary brain metastasis, surgical resection followed by whole brain radiotherapy (WBRT) or alternatively radiosurgery with or without WBRT might be beneficial 1
• For solitary adrenal metastasis (histologically proven), prolonged survival after resection of adrenal and primary tumor has been suggested in selected patients 1
• Solitary lesions in the contralateral lung should be considered as synchronous secondary primary tumors and treated accordingly 1

Follow-Up

• Close follow-up, at least every 6 weeks after first-line therapy, is advised but should depend on individual re-treatment options 1
• Radiological follow-up should be considered every 6-12 weeks to allow for early initiation of second-line therapy 1

Common Pitfalls to Avoid

• Inadequate tissue sampling leading to insufficient material for molecular testing 1
• Delaying molecular testing, which can impact the timely initiation of targeted therapy 1
• Not considering re-biopsy at disease progression, which may reveal transformation or new molecular targets 1
• Failing to recognize that adenocarcinoma can transform into small-cell lung cancer when resistance to tyrosine kinase inhibitors develops (occurs in approximately 3-10% of EGFR-mutant NSCLC) 4