Real-world deployment of a fine-tuned pathology foundation model for lung cancer biomarker detection

Artificial intelligence models using digital histopathology slides stained with hematoxylin and eosin offer promising, tissue-preserving diagnostic tools for patients with cancer. Despite their advantages, their clinical utility in real-world settings remains unproven. Assessing EGFR mutations in lung adenocarcinoma demands rapid, accurate and cost-effective tests that preserve tissue for genomic sequencing. PCR-based assays provide rapid results but with reduced accuracy compared with next-generation sequencing and require additional tissue. Computational biomarkers leveraging modern foundation models can address these limitations. Here we assembled a large international clinical dataset of digital lung adenocarcinoma slides (N = 8,461) to develop a computational EGFR biomarker. Our model fine-tunes an open-source foundation model, improving task-specific performance with out-of-center generalization and clinical-grade accuracy on primary and metastatic specimens (mean area under the curve: internal 0.847, external 0.870). To evaluate real-world clinical translation, we conducted a prospective silent trial of the biomarker on primary samples, achieving an area under the curve of 0.890. The artificial-intelligence-assisted workflow reduced the number of rapid molecular tests needed by up to 43% while maintaining the current clinical standard performance. Our retrospective and prospective analyses demonstrate the real-world clinical utility of a computational pathology biomarker.