Stage I–III Non-Small Cell Lung Cancer Treatment

Authored by Chinmay Jani, published on 2026-09-02 21:17:33.0

The algorithm is broadly aligned with current management of stage I–IIIB NSCLC: guideline-concordant diagnostic workup, surgery or SBRT for early-stage disease, biomarker-driven adjuvant targeted therapy after resection, and concurrent chemoradiation followed by consolidation durvalumab for unresectable stage III. It appropriately incorporates modern perioperative chemoimmunotherapy options (KEYNOTE-671, AEGEAN, CheckMate 77T) and adjuvant osimertinib (ADAURA) and alectinib (ALINA). However, some postoperative margin/nodal recommendations are underspecified, and the stage III EGFR+ post-CRT strategy is evolving and not as established as PACIFIC in EGFR-negative disease.

  1. Early Stage NSCLC
    • Workup
      CT C/A/P PET/CT Invasive mediastinal staging (EBUS) brain MRI ±
      • Assess resectability
        If yes: NGS and biomarker-directed peri-op therapy pathway.
        • Stage IB–IIIA, select Stage IIIB
          T? / N? (handwritten).
          • Molecular testing (NGS) + PD-L1
            Broad molecular testing in early-stage/resectable NSCLC is recommended to identify actionable alterations that direct perioperative/adjuvant therapy (e.g., EGFR→osimertinib; ALK→alectinib) and to avoid ineffective sequencing (e.g., perioperative immunotherapy in classic driver-positive tumors).
            • EGFR+
              • Surgery
                • Platinum doublet chemo
                  • Osimertinib X3 Years (ADAURA)
                    Three years of adjuvant osimertinib is supported after complete resection of eligible EGFR exon 19 deletion or exon 21 L858R stage IB-IIIA NSCLC, with chemotherapy given when otherwise indicated.
            • ALK+
              • Surgery
                • Alectinib x2 Years (ALINA)
            • RET+
              • Surgery
                • Selpercatinib x3 years (LIBRETTO-432)
                  Selpercatinib is active in advanced RET fusion-positive NSCLC, but adjuvant use after resection remains investigational. The phase III LIBRETTO-432 study evaluates this strategy and routine use outside a trial is not established.
            • No EGFR mutation or ALK rearrangement
              • Nivo + Chemo X4 (CheckMate 77T)
                CheckMate 77T supports four cycles of neoadjuvant nivolumab plus platinum-doublet chemotherapy as part of a perioperative regimen.
                • Surgery
                  • Nivo X13
              • Upfront Surgery
                • Surgery
                  • Adjuvant platinum chemotherapy when indicated
                    • Atezolizumab*
                      *For patients with ≥4 cm or node-positive NSCLC, stages IB–IIIA or select IIIB (T2–T3, N2b; T4, N2), who received adjuvant chemotherapy, with PD-L1 ≥1% and no known EGFR mutation or ALK gene fusion.
                    • Pembro*
                      *For patients with ≥4 cm or node-positive NSCLC, stages IB–IIIA or select IIIB (T2–T3, N2b; T4, N2), who received adjuvant chemotherapy and have no known EGFR mutation or ALK gene fusion.
              • Durva + Chemo X4 (AEGEAN)
                Four neoadjuvant cycles of durvalumab plus platinum-based chemotherapy match the AEGEAN regimen.
                • Surgery
                  • Durva
                    Maintenance shown as 'Durva' with circled count (unclear).
              • Pembro + Chemo X4 (KEYNOTE 671)
                Four neoadjuvant cycles of pembrolizumab plus cisplatin-based chemotherapy match the KEYNOTE-671 protocol.
                • Surgery
                  • Pembro X13
              • Nivo Chemo Doublet X3 (CheckMate 816)
                This node is only partially supported as drawn: CheckMate 816 used nivolumab plus platinum-doublet chemotherapy for three cycles, not chemotherapy alone.
                • Surgery
                  • Stop / no routine adjuvant immunotherapy
        • Unresectable Stage III
          • Histology check and NGS testing
            • Non-squamous: Carboplatin AUC 5 on Day 1+ Pemetrexed 500 mg/m2 on D1-21 for 4 cycles + concurrent thoracic RT
              Concurrent chemoradiation is the standard definitive treatment backbone for unresectable stage III NSCLC in patients who can tolerate it.
              • EGFR Ex19del or L858R
                • Osimertinib
              • No sensitizing EGFR mutation
                • Durvalumab x12 Months (PACIFIC)
            • Squamous: Carbo AUC 2 + Paclitaxel 45-50 mg/m2 weekly with concurrent thoracic RT
              • EGFR Ex19del or L858R
                • Osimertinib
              • No sensitizing EGFR mutation
                • Durvalumab x12 Months (PACIFIC)
        • Stage I (T1-2, N0)
          Options: resection or radiation.
          • Resection
          • Radiation (SABR/SBRT)
  2. Surgery based on pathology
    Negative Margins vs. Positive Margins (Consider radiation) Nodes: N1 (Adjuvant indicated) vs. N2 (High risk for locoregional recurrence)
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