Surgery & procedures
| Anatomic resection (lobectomy/segmentectomy) with systematic nodal dissection when operable Anatomic resection (lobectomy/segmentectomy) with systematic nodal dissection when operable. | Curative | Standard | Curated |
| Sublobar resection considered for small peripheral lesions or limited reserve Sublobar resection considered for small peripheral lesions or limited reserve. | Curative | Standard | Curated |
| VATS/robotic approaches common VATS/robotic approaches common; ERAS pathways for recovery. | Curative | Standard | Curated |
| For oligometastatic disease responding to systemic therapy, consider metastasectomy case-by-case For oligometastatic disease responding to systemic therapy, consider metastasectomy case-by-case. | Curative | Standard | Curated |
Radiotherapy
| SBRT for medically inoperable early-stage disease (curative intent) SBRT for medically inoperable early-stage disease (curative intent). | — | Standard | Curated |
| Post-op or definitive chemoradiation for positive margins/unresectable disease Post-op or definitive chemoradiation for positive margins/unresectable disease. | — | Standard | Curated |
| SRS for brain metastases SRS for brain metastases; WBRT for diffuse involvement. | — | Standard | Curated |
| Palliative RT for symptomatic bone, chest wall, airway, or CNS lesions Palliative RT for symptomatic bone, chest wall, airway, or CNS lesions. | Palliative | Standard | Curated |
Chemotherapy
| Pemetrexed-based regimens favored in non-squamous NSCLC Pemetrexed-based regimens favored in non-squamous NSCLC; maintenance pemetrexed ± IO after induction. | Maintenance | Standard | Curated |
| Later lines guided by resistance profile (e Later lines guided by resistance profile (e.g., MET amp after EGFR) and clinical trial availability. | — | Standard | Curated |
| Platinum + Pemetrexed (± Pembrolizumab) (first-line driver-negative non-squamous) Standard induction (4 cycles) followed by maintenance pemetrexed ± pembrolizumab; folate/B12 + steroid premed required. | — | Standard | Curated |
| Platinum + Taxane (± Pembrolizumab/Bevacizumab) (first-line non-squamous alternative) Useful when pemetrexed contraindicated; consider bevacizumab if no bleeding/hemoptysis or recent surgery. | — | Standard | Curated |
| Single-agent Pemetrexed Maintenance (post-induction) Non-squamous maintenance option; continue until progression/toxicity; add IO per initial plan. | Maintenance | Standard | Curated |
| Docetaxel (± Ramucirumab) (subsequent line) Post–IO/chemo progression; monitor for neutropenia, mucositis, edema; ramucirumab adds VEGF-related AEs. | — | Standard | Curated |
| Gemcitabine/Vinorelbine/Other Doublets (selected cases) Alternatives when standard options exhausted/contraindicated; response rates modest. | — | Standard | Curated |
Targeted therapy
| Driver-positive: matched TKI first-line (EGFR, ALK, ROS1, RET, METex14, BRAF V600E, NTRK, HER2) Driver-positive: matched TKI first-line (EGFR, ALK, ROS1, RET, METex14, BRAF V600E, NTRK, HER2). | — | Standard | Curated |
| EGFR, ALK, ROS1, RET, METex14, BRAF V600E, NTRK, HER2: prioritize matched TKIs with CNS-active options where possible EGFR, ALK, ROS1, RET, METex14, BRAF V600E, NTRK, HER2: prioritize matched TKIs with CNS-active options where possible. | — | Standard | Curated |
| KRAS G12C: G12C inhibitors active KRAS G12C: G12C inhibitors active; co-mutations (STK11/KEAP1) shape IO benefit. | — | Standard | Curated |
| Avoid initiating IO just before TKIs with high pneumonitis/hepatitis overlap Avoid initiating IO just before TKIs with high pneumonitis/hepatitis overlap; sequence thoughtfully. | — | Standard | Curated |
| Re-biopsy/ctDNA at progression to reveal on-target mutations (e Re-biopsy/ctDNA at progression to reveal on-target mutations (e.g., EGFR C797S) or bypass (MET/HER2 amp) for next-line strategy. | — | Standard | Curated |
| Combinations to overcome resistance (TKI + MET/MEK/other) best pursued on trials Combinations to overcome resistance (TKI + MET/MEK/other) best pursued on trials. | — | Standard | Curated |
| Crizotinib FDA-approved for this cancer. | — | Guideline option |
Immunotherapy
| Driver-negative: PD-L1 ≥50% → single-agent PD-1/PD-L1 Driver-negative: PD-L1 ≥50% → single-agent PD-1/PD-L1; otherwise IO + platinum doublet (commonly pembrolizumab + carboplatin/cisplatin + pemetrexed). | — | Standard | Curated |
| PD-L1 high driver-negative disease: consider IO monotherapy PD-L1 high driver-negative disease: consider IO monotherapy; otherwise IO-chemotherapy. | — | Standard | Curated |
Other
| Etoposide FDA-approved for this cancer. | — | Guideline option |
Established care shown from OncoForge editorial curation · reviewed September 25, 2025 — authoritative citations (NCI PDQ / FDA) are being added.