Management of Non-Small Cell Lung Cancer According to Latest NCCN Guidelines
The management of non-small cell lung cancer (NSCLC) according to the latest NCCN guidelines requires comprehensive molecular testing for actionable biomarkers, followed by stage-appropriate treatment with surgery, targeted therapy, immunotherapy, chemotherapy, or radiation therapy based on individual disease characteristics.
Initial Evaluation and Staging
- All patients with suspected NSCLC should undergo thorough evaluation including history, physical examination, CT scan of chest and upper abdomen with contrast (unless contraindicated) to exclude metastatic disease 1
- FDG-PET/CT scan and brain imaging should be performed for accurate staging 1
- For patients with suspected stage III NSCLC who are candidates for curative-intent treatment, mediastinal lymph node status must be confirmed by pathologic assessment 1
- Endoscopic techniques should be the initial staging modality for pathologic assessment of lymph node status 1
- Multidisciplinary discussion should occur prior to initiating any treatment plan 1
Molecular Testing
- Molecular profiling is essential before selecting initial therapy for metastatic NSCLC 1
- Key established predictive biomarkers that should be tested include:
- ALK rearrangements
- BRAF V600E mutations
- EGFR mutations
- METex14 skipping mutations
- NTRK1/2/3 gene fusions
- RET rearrangements
- ROS1 rearrangements
- PD-L1 expression 1
- Broad molecular profiling is strongly advised to identify rare driver mutations for which effective drugs may be available 1
- For squamous cell carcinoma, the incidence of EGFR mutations is low (2.7%) and does not justify routine testing of all specimens 1
Stage-Specific Management
Early Stage NSCLC (Stage I-II)
- Radical surgery is the standard of care for fit stage I NSCLC patients 2
- For stage II, surgery followed by adjuvant cisplatin-based chemotherapy is recommended 2
- For patients with resectable (tumors ≥4 cm or node positive) NSCLC, neoadjuvant platinum-containing chemotherapy followed by surgery and then continued as single agent adjuvant treatment is an option 3
- For stage IB (T2a ≥4 cm), II, or IIIA NSCLC, adjuvant treatment following resection and platinum-based chemotherapy is recommended 3
Stage III NSCLC
- Patients with stage IIIA (N2) NSCLC may be offered induction therapy followed by surgery if:
- Complete resection (R0) of primary tumor and involved lymph nodes is possible
- N3 lymph nodes are not involved
- Perioperative mortality is expected to be low (≤5%) 1
- For selected patients with T4N0 disease, surgical resection may be offered if medically and surgically feasible 1
- Patients planned for multimodality approach incorporating surgery should receive systemic neoadjuvant therapy 1
- For patients with N2 disease planned for surgical resection, neoadjuvant chemotherapy or concurrent chemoradiation is recommended 1
- Radiotherapy plus chemotherapy should be considered for patients with unresectable stage III disease 1
Stage IV NSCLC
- Patients with widespread metastatic disease are candidates for systemic therapy, clinical trials, and/or palliative treatment 1
- Treatment decisions should be based on molecular biomarker testing results 1
- For patients with actionable mutations, targeted therapies are recommended:
- For EGFR mutations: EGFR TKIs (osimertinib preferred) 1
- For ALK rearrangements: ALK inhibitors (alectinib preferred) 1
- For ROS1 rearrangements: crizotinib (preferred) or ceritinib 1
- For BRAF V600E mutations: targeted BRAF inhibitors 1
- For ERBB2 (HER2) mutations: fam-trastuzumab deruxtecan-nxki (after progression) 1
- For patients without actionable mutations:
- First-line therapy options based on PD-L1 expression:
- For patients with oligometastatic disease, definitive local therapy (SABR or surgery) should be considered 1
Management of Recurrence and Progression
- For patients with locoregional recurrences (endobronchial obstruction, mediastinal lymph node recurrence, superior vena cava obstructions, severe hemoptysis), local therapies should be considered 1
- For patients with solitary brain metastases, surgical resection and/or radiation therapy may be beneficial 1
- For patients with adrenal metastases and otherwise resectable primary tumors, adrenal biopsy should be performed to rule out benign adenoma 1
- For patients with EGFR mutations who progress on EGFR TKIs:
Surveillance
- After curative treatment, helical chest CT scan with or without contrast is recommended every 6 to 12 months for 2 years, then annually thereafter 1
- Smoking cessation counseling should be provided to improve quality of life 1
- Low-dose CT screening is not currently recommended for surveillance of those who have previously undergone treatment for lung cancer 1
Common Pitfalls and Caveats
- Failure to perform comprehensive molecular testing before initiating treatment can lead to suboptimal therapy choices 1
- For patients with squamous histology, molecular testing may still be valuable in select cases, particularly in never-smokers 1
- Beware of flare phenomenon in subset of patients who discontinue EGFR TKI therapy 1
- For rapid radiologic progression or threatened organ function, alternate therapy should be instituted promptly 1
- PD-1/PD-L1 inhibitor monotherapy is less effective in EGFR-mutated NSCLC, regardless of PD-L1 expression 1