Diagnostics

• CBC: may detect anemia, neutropenia, and/or thrombocytopenia

• CMP

  • Hypercalcemia: may indicate bone metastasis or paraneoplastic syndrome

  • Elevated alkaline phosphatase: may indicate bone and/or liver metastasis

  • Abnormal liver function test: may indicate liver metastasis

• LDH: possibly elevated

• Modalities

  • Chest x-ray: indicated as first-line imaging study

  • CT chest: indicated in all patients with an abnormal chest x-ray or suspicion of lung cancer

• Findings

  • Visualization of nodules and/or masses with features suggestive of malignancy, including:

    • Irregular margins (i.e., scalloped or spiculated)

    • Large size (> 2 cm)

    • Upper lobe location

    • The absence of calcifications

    • 
      

  • Indirect signs of malignancy

    • Atelectasis

    • Postobstructive pneumonia

    • Pleural effusion (particularly unilateral)

    • Mediastinal widening

  • Examples of findings in specific subtypes

    • Hazy infiltrates (characteristic of adenocarcinoma in situ)

    • Cavitating lesion with air-fluid levels (characteristic of squamous cell carcinoma)

Histopathological analysis of tissue biopsies is required to confirm the diagnosis of lung cancer; cytology may be confirmatory in select cases.

• Obtaining samples: Less invasive methods are preferred.

  • Pulmonary lesions

    • Central: bronchoscopy with transbronchial biopsy

    • Peripheral: needle aspiration guided by endobronchial ultrasound or CT

  • Pleural effusion: thoracocentesis with cytology of the effusion; pleural biopsy if cytology is negative

• Findings

  • Confirms the diagnosis and identifies the SCLC or NSCLC subtype (e.g., adenocarcinoma, squamous cell carcinoma, large cell carcinoma)

Since the majority of patients present with metastatic disease, a complete staging evaluation is required. Molecular testing can identify mutations and markers that help inform treatment selection.

Imaging for lung cancer staging

Obtain cross-sectional imaging of the brain, chest, and abdomen. PET-CT is increasingly used for staging because of its high sensitivity for metastatic disease. See “Lung cancer staging” for interpretation.

• CT thorax and abdomen

  • Recommended in all patients

  • Metastatic disease is most common in the liver and adrenal glands.

• Brain imaging

  • MRI brain with gadolinium enhancement: preferred

  • CT brain with contrast: alternative

• PET-CT

  • Indicated for the assessment of thoracic and abdominal metastases in NSCLC; may be used in SCLC

  • Preferred method to assess bone metastases in all subtypes

Molecular testing may provide guidance for the therapy of SCLC, but it is considered mandatory for patients with advanced or metastatic NSCLC as the presence of certain biomarkers modifies therapy.

• Genetic testing: next-generation sequencing (entire genome) or RT-PCR for specific mutations

  • Indications: patients with advanced or metastatic NSCLC and nonsmokers with SCLC

  • Goal: to identify oncogenic mutations that may be therapeutically targeted

  • Recommended biomarkers

    • Epidermal growth factor receptor (EGFR) mutations

    • Anaplastic lymphoma kinase (ALK) fusions

    • c-ROS oncogene 1 (ROS1) rearrangements

programmed death-ligand 1 (PD-L1) testing

• Description: PD-L1 is a coregulatory molecule expressed on tumor cells that inhibits T-cell mediated death; cytotoxic T cells express PD-1 (a negative regulator) that binds PD-L1.

• Indication: patients with advanced or metastatic NSCLC

• Goal: to identify patients who may respond to immune checkpoint inhibitors