Stage I–IIIB Non-Small Cell Lung Cancer Treatment

Authored by Chinmay Jani, published on 2026-08-27 20:02:40.0

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 ±
      • Stage II–IIIA
        T? / N? (handwritten).
        • Resectable / Operable?
          If yes: NGS and biomarker-directed peri-op therapy pathway.
          • NGS
            • EGFR+
              • Surgery
                • 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.
            • Without Alterations
              • 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
              • If Neoadjuvant Not Done
                • Surgery
                  • Atezolizumab
                    PD-L1 ≥ 1%.
                  • Pembro
              • 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
      • Stage I (T1-2, N0)
        Options: resection or radiation.
        • Resection
        • Radiation
      • Stage IIIB / Non-resectable
        • Concurrent Chemo-Radiation
          Non-resectable / definitive approach noted.
          • NGS
            • EGFR+
              • Osimertinib
            • EGFR Negative
              • Durvalumab x12 Months (PACIFIC)
  2. Radiation
    • Stage I (T1-2, N0)
      • Not Indicated For Surgery
        • SABR/SBRT
    • Surgery based on pathology (stage IB–IIA)
      • Margins
        • Negative Margins
        • Positive Margins
          Consider radiation.
      • Nodes
        • N1
          Adjuvant indicated.
        • N2
          High risk for locoregional recurrence.
    • IIIB pathway
tosprivacy