What is the diagnosis of Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma?

From the Guidelines

The diagnosis of Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma should be made according to the World Health Organization (WHO) classification and the International Association for the Study of Lung Cancer (IASLC) classification of adenocarcinoma, with specific subtyping and molecular testing, including EGFR mutation status, to guide therapeutic decision-making 1. The diagnostic approach for NSCLC adenocarcinoma involves a combination of imaging studies and tissue sampling. Initially, patients typically undergo chest imaging with CT scans to identify suspicious lung lesions, followed by PET-CT for staging if cancer is suspected.

Key Diagnostic Steps:

• Definitive diagnosis requires tissue sampling, which can be obtained through bronchoscopy, CT-guided needle biopsy, endobronchial ultrasound (EBUS), or surgical procedures like mediastinoscopy or thoracoscopy 1.
• The tissue sample undergoes pathological examination where adenocarcinoma is identified by its glandular architecture and mucin production.
• Immunohistochemical staining for markers like TTF-1 and Napsin A helps confirm adenocarcinoma.
• Molecular testing is essential for treatment planning and should include analysis for EGFR mutations, ALK and ROS1 rearrangements, BRAF mutations, NTRK fusions, MET alterations, RET fusions, and PD-L1 expression 1.

Importance of Recent Guidelines:

• The 2014 ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of metastatic NSCLC recommend obtaining adequate tissue material for histological diagnosis and molecular testing to allow individual treatment decisions 1.
• These guidelines also emphasize the importance of specific subtyping of all NSCLCs and the use of immunohistochemistry (IHC) to reduce the NSCLC not otherwise specified (NSCLC-NOS) rate to fewer than 10% of cases diagnosed 1.

Staging and Treatment:

• Complete staging using the TNM system determines the extent of disease and guides treatment options.
• The treatment strategy should take into account the histology, molecular pathology, age, performance status, comorbidities, and patient’s preferences, with systemic therapy offered to all stage IV patients with performance status 0–2 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Diagnosis of Non-Small Cell Lung Cancer (NSCLC) Adenocarcinoma

The diagnosis of NSCLC adenocarcinoma is typically established through:

• Fiberoptic bronchoscopy or percutaneous fine-needle aspiration 2
• Biopsy of a regional or distant metastatic site 2
• Endobronchial ultrasound fine-needle aspiration (EBUS FNA) with cell block and immunohistochemical (IHC) panel 3
• Surgical pathology concomitant material 3

Diagnostic Techniques

The following diagnostic techniques are used to diagnose NSCLC adenocarcinoma:

• EBUS FNA with cell block and IHC panel, including monoclonal antibodies for napsin A, thyroid transcription factor (TTF-1), p63, and cytokeratin 5/6 (CK5/6) 3
• Random forest analysis to identify genes associated with pathologic stages of lung adenocarcinoma 4
• Univariate regression to analyze the relationship between gene expression and prognosis 4
• Protein-protein interaction network to show the interactions among the identified genes 4

Staging and Prognosis

The staging of NSCLC adenocarcinoma is critical for determining treatment and prognosis:

• The extent of tumor dissemination is a dominant prognostic factor in NSCLC 2
• Stages I and II NSCLC are managed by surgical resection whenever possible, with approximate 5-year survival of 45% and 25%, respectively 2
• Patients with stage IIIa cancers can occasionally be surgically resected but are often managed with definitive thoracic irradiation and have 5-year survival of approximately 15% 2

Molecular Diagnosis

Molecular diagnosis is becoming increasingly important for NSCLC adenocarcinoma:

• Genes associated with pathologic stages of lung adenocarcinoma have been identified using random forest analysis 4
• Molecular tests can stratify patients and inform treatment decisions 5
• Progress in molecular diagnosis may enhance potential for accurate definition, diagnosis, and optimizing treatment approach for multifocal lung adenocarcinoma 5