NSCLC Treatment Recommendations Based on the AJCC 8th Edition TNM Staging System

Initial Diagnostic and Staging Workup

The American Joint Committee on Cancer (AJCC) recommends a complete smoking history, weight loss percentage, ECOG performance status, and assessment of specific comorbidities for all NSCLC patients 1, 2
Laboratory evaluation should include complete blood count, comprehensive metabolic panel, and bone biochemistry for all NSCLC patients 1, 2
Contrast-enhanced CT chest and upper abdomen is mandatory for all patients, while brain imaging should be performed for all metastatic disease patients and those with neurological symptoms 1, 2
PET-CT scan offers high sensitivity for mediastinal lymph node assessment and distant metastasis detection 3, 2
Bone imaging is required when bone metastases are clinically suspected 1, 2

EGFR mutation testing is mandatory in all non-squamous NSCLC patients 1, 3
ALK rearrangement testing is required in non-squamous histology patients 1, 3
ROS1 translocation testing should be systematically performed in NSCLC patients 1
BRAF V600 mutation analysis is required for advanced NSCLC patients 1
PD-L1 IHC testing is mandatory for all advanced NSCLC patients to guide immunotherapy decisions 1

For stage IA-IB disease, anatomical resection is the preferred surgical approach, while sub-lobar resection may be considered for pure ground-glass opacity lesions or adenocarcinoma in situ 4
For stage II-IIIA disease, surgical resection followed by adjuvant platinum-based chemotherapy is recommended 4
For stage IIIA-IIIB-IIIC disease, definitive concurrent chemoradiotherapy is the preferred treatment, with cisplatin-based regimens delivered concurrently with radiotherapy 4
For stage IV disease with EGFR mutation, first-line tyrosine kinase inhibitors should be prescribed, even in patients with poor performance status 3, 2, 4
For stage IV disease with ALK-positive NSCLC, ALK inhibitors are the first-line treatment 3, 2
For stage IV disease with no druggable driver mutation, platinum-based doublet chemotherapy is standard for patients with PS 0-2 1, 3

Response evaluation should be performed after 6-9 weeks of systemic therapy using the same initial radiographic modality 1, 2
RECIST criteria v1.1 should be used for measurement and response assessment 1
PET follow-up is not routinely recommended due to high sensitivity but relatively low specificity 1, 2

Early palliative care intervention should be initiated in parallel with standard oncologic care to improve quality of life and median survival 2
Radiotherapy plays a major role in symptom control for bone and brain metastases 2
Zoledronic acid or denosumab is recommended for patients with bone metastases to reduce skeletal-related events 2
Smoking cessation should be highly encouraged at any stage to improve outcomes 1, 3, 4