Prognostic implication of malignant pleural metastases in stage M1a non-small cell lung cancer in a real-world Dutch cohort receiving chemotherapy and/or immunotherapy.

INTRODUCTION: In the updated 9th TNM non-small cell lung cancer (NSCLC) staging edition, pleural and pulmonary metastases remain grouped within the M1a category, inferring similar prognostic implications. The aim was to evaluate the prognostic implication on overall survival (OS) of pleural versus contralateral pulmonary metastases in a stage M1a cohort, when treated with immune checkpoint inhibitors (ICI), chemotherapy, or chemo-ICI. METHODS: Retrospective real-world data from the Netherlands Cancer Registry was used, including patients with M1a NSCLC that received systemic treatment between 2010-2022. The primary outcome was 2-year OS. RESULTS: 5632 patients were included: 2701 with contralateral lung metastases, 2590 with pleural metastases and 341 with both. Pleural metastases were more common in men (p=<0.001), in patients with worse performance score (p=<0.001) and in patients receiving mono-ICI (p=<0.001).Patients with contralateral lung metastases had a better 2-year OS (for chemo, ICI and chemo-ICI, this was 26.9% (95% CI 24.9-28.9), 49.5% (95% CI 43.4-55.2) and 40.4% (95% CI 36.5-44.2), respectively) than patients with pleural metastases (18.5% (95% CI 16.6-20.4), 41.6% (95% CI 36.6-46.5) and 28.6% (95% CI 24.9-32.4), respectively). Patients with both contralateral lung and pleural metastases had the worst OS (12.1% (95% CI 8.2-16.7), 31.1% (95% CI 18.4-44.7) and 25.0% (95% CI 15.7-35.4), respectively). The difference in OS was irrespective of the type of systemic treatment. CONCLUSION: Patients with pleural metastases have inferior OS compared to those with contralateral lung metastases. These findings indicate prognostic heterogeneity between M1a descriptors.