[11][12] Recent studies, though, suggest that the "ratio of centrally to peripherally occurring" lesions may be converging toward unity for both adenocarcinoma and squamous-cell carcinoma.

LCLCs have typically comprised around 10% of all NSCLCs in the past, although newer diagnostic techniques seem to be reducing the incidence of diagnosis of "classic" LCLC in favor of more poorly differentiated SCCs and adenocarcinomas.

[15] A few more symptoms associated with the early progression of the disease are feeling weak, being very tired, having trouble swallowing, swelling in the face or neck, and continuous or recurring infections such as bronchitis or pneumonia.

[5][15][16] Signs of more advanced cases include bone pain, nervous-system changes (headache, weakness, dizziness, balance problems, seizures), jaundice, lumps near the surface of the body, numbness of extremities due to Pancoast syndrome, and nausea, vomiting, and constipation brought on by hypercalcemia.

[15][16] Some more of the symptoms that indicate further progression of the cancer include shortness of breath, superior vena cava syndrome, trouble swallowing, large amounts of mucus, weakness, fatigue, and hoarseness.

[5][17] Genetics can also play a role as a family history of lung cancer can contribute to an increased risk of developing the disease.

[31] With TNM staging, the cancer is classified based on the size of the primary tumor and whether it has invaded adjacent structures (T), spread to lymph nodes (N) and other organs (M).

[32] The lung tumor itself is typically assessed both radiographically for overall size and by a pathologist under the microscope to identify specific genetic markers or to see if invasion into important structures within the chest (e.g., bronchus or pleural cavity) has occurred.

Finally, the patient is evaluated for more distant sites of metastatic disease, most typically with brain imaging and or scans of the bones.

[citation needed] NSCLCs are usually not very sensitive to chemotherapy[35] and/or radiation, so surgery (lung resection to remove the tumor) remains the treatment of choice if patients are diagnosed at an early stage.

Certain people who are deemed to be at higher risk may also receive adjuvant (ancillary) chemotherapy after initial surgery or radiation therapy.

Nodules less than 1 cm from the trachea, main bronchi, oesophagus, and central vessels should be excluded from RFA given the high risk of complications and frequent incomplete ablation.

[39] As a minimally invasive procedure, it can be a safer alternative for patients who are poor candidates for surgery due to comorbidities or limited lung function.

A study comparing thermal ablation to sublobar resection as treatment for early-stage NSCLC in older people found no difference in overall survival of the patients.

[41] The treatment scenario for patients with resectable non-small cell lung cancer has changed dramatically with the incorporation of immunotherapy.

The treatment approach for people who have advanced NSCLC is first aimed at relieving pain and distress (palliative), but a wide variety of chemotherapy options exists.

[49][50] At present, two genetic markers are routinely profiled in NSCLC tumors to guide further treatment decision-making - mutations within epidermal growth factor (EGFR) and anaplastic lymphoma kinase.

[51] Also, several additional genetic markers are known to be mutated within NSCLC and may impact treatment in the future, including BRAF, HER2/neu, and KRAS.

These people are sensitized to certain medications that block the EGFR protein known as tyrosine kinase inhibitors specifically, erlotinib, gefitinib, afatinib, or osimertinib.

[54] Reliable identification of mutations in lung cancer needs careful consideration due to the variable sensitivity of diagnostic techniques.

[36] NSCLC patients with advanced disease who are not found to have either EGFR or ALK mutations may receive bevacizumab, which is a monoclonal antibody medication targeted against the vascular endothelial growth factor (VEGF).

Bevacizumab is a monoclonal antibody that targets the Vascular Endothelial Growth Factor (VEGF) in the circulation and functions as an angiogenesis inhibitor.

Multiple phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC were published, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.

[63][64] Mobocertinib (Exkivity) was approved for medical use in the United States in September 2021, and it is indicated for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.