Navigating controversies in stage III NSCLC: a multidisciplinary case discussion on evolving treatment paradigms

BACKGROUND: The management of stage III non-small cell lung cancer (NSCLC) has become increasingly complex, driven by advances in neoadjuvant and perioperative chemo-immunotherapy as well as targeted therapies. These evolving treatment paradigms have introduced new challenges for multidisciplinary teams (MDTs), regarding patient selection, treatment sequencing, surgical planning and definitions of operability and resectability. CASE PRESENTATION: We present a case of a 69-year-old male with cT3N2aM0 (single-station N2) adenocarcinoma NSCLC with a programmed death-ligand 1 (PD-L1) tumour proportion score of 100%. Following discussion in MDT, he received 3 cycles of neoadjuvant carboplatin, paclitaxel, and nivolumab. The initial surgical plan was for a pneumonectomy due to tumour proximity to the right main bronchus, a procedure associated with perioperative risk and long-term functional compromise. Restaging computed tomography (CT) scan demonstrated a partial response, with a 60% reduction in axial tumour dimensions. This downstaging facilitated a change in surgical plan from pneumonectomy to the less extensive right upper lobectomy, resulting in a pathological complete response (ypT0ypN0). DISCUSSION: The case was discussed during an academic webinar in August 2025. Expert faculty from respiratory medicine, thoracic surgery and medical and radiation/clinical oncology highlighted key discussion points and challenges. This included: 1) evolving definitions of operability and resectability, 2) perioperative systemic therapy selection, 3) the risk of not proceeding to surgery, and 4) the role of postoperative radiotherapy (PORT) and salvage therapy in case of progression. CONCLUSION: The case underscores current controversies in the management of stage III NSCLC and the critical role of the MDT. While neoadjuvant and perioperative chemo-immunotherapy offers an opportunity for less extensive surgical resection and improved oncological outcomes, this strategy is not without risks and validated biomarkers to guide decision making are lacking. Concurrent chemoradiotherapy (cCRT) followed by durvalumab remains the standard for fit patients with unresectable or inoperable stage III disease. Future progress depends on clinical trials, biomarker development, and real-world data collection and national audits.