Non–Small Cell Lung Cancer 2026 UPDATE

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.

In this episode, OncLive On Air^® partnered with Two Onc Docs to deliver a comprehensive, board-focused review of early-stage and locally advanced non–small cell lung cancer (NSCLC) for 2026, reflecting recent shifts in staging and perioperative therapy.

The discussion began with histology, distinguishing adenocarcinoma (positive for TTF-1 and CK7) from squamous cell carcinoma (positive for p63 and p40). Turning to staging, Drs Armstrong and Tawagi emphasized the 9th edition of the lung cancer TNM staging system, noting that T categories are unchanged but N2 is now split into N2a and N2b, and M1c is now split into M1c1 and M1c2. They also stressed the importance of biomarker testing for PD-L1, EGFR, ALK, and RET.

Regarding treatment, they explained that stage IA disease warrants surgery or stereotactic body radiation therapy without systemic therapy. In resectable disease that is 4 cm or larger or node-positive disease, driver mutations guide management: osimertinib (Tagrisso) for EGFR-mutated disease, alectinib (Alecensa) for ALK-positive disease, and selpercatinib (Retevmo) for RET-mutated disease, with immunotherapy avoided in EGFR-mutated or ALK-positive tumors. For driver-negative disease, they reviewed 4 category 1 regimens, including neoadjuvant nivolumab (Opdivo) and perioperative pembrolizumab (Keytruda) or nivolumab, cautioning against switching agents in the middle of a treatment course.

Drs Armstrong and Tawagi then addressed adjuvant immunotherapy, unresectable stage III disease management with concurrent chemoradiation followed by consolidative durvalumab (Imfinzi) or osimertinib, surgical candidacy, adjuvant chemotherapy regimens, postoperative radiation, and special circumstances, including superior sulcus tumors.