The management of complex patients with inoperable stage III NSCLC: practical lessons from case-based discussion.

BACKGROUND: Standard of care for inoperable and/or unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy followed by 12 months of adjuvant durvalumab. Many patients are ineligible due to poor fitness, comorbidity or concerns around their ability to tolerate concurrent therapy or immunotherapy. As a result, these patients experience inferior outcomes. CASE STUDIES: This article summarises four case studies initially presented at a UK-based academic webinar in August 2025. The focus of the webinar was the radiotherapy-based management of complex patients with stage III NSCLC. This included tumour factors (i.e. vascular invasion and bulky disease) and patient factors (i.e. interstitial lung disease, multiple comorbidities and frailty). Strategies to navigate these challenges and improve outcomes are highlighted. DISCUSSION: Patients ineligible for standard-of-care treatment are under-represented in practice-defining trials. As a result, there is limited evidence to guide their management. Broader eligibility criteria and inclusive trials are needed to generate safety and efficacy data for this population. Enhanced phenotyping with biomarkers, adoption of advanced radiotherapy techniques, risk-adapted dose guidance and novel drug-radiotherapy combinations offer potential to expand access to curative-intent treatment and improve outcomes.