LUCAID: Agentic Multimodal AI for Lung Cancer Precision Pathology

Pathological assessment guides lung cancer diagnosis, treatment selection, and prognostic evaluation, yet current CPath approaches rely on task-specific models for isolated objectives. Although pan-cancer foundation models offer versatility, they lack subspecialty-level depth and have not been evaluated across clinical workflows or prospectively validated in real-world settings. We introduce PulmoFoundation, a multi-center, prospectively validated, randomized controlled trial (RCT)-evaluated foundation model for comprehensive lung pathology assessment across pre-operative, intra-operative, and post-operative care. Built upon Virchow2 via subspecialty-specific pretraining using ~40,000 diagnostic H&E-stained whole-slide images (WSIs), PulmoFoundation was systematically evaluated on ~26,000 WSIs across 32 clinically relevant tasks. In addition to accurately predicting molecular markers and patient survival, our model achieves clinical-grade performance in core diagnostic tasks across biopsy, frozen section, and surgical resection slides. In a registered prospective study of 1,357 patients across 11 diagnostic tasks, our model achieved an average AUC of 92.3%. Using pre-specified triage thresholds, PulmoFoundation could reduce additional second-review burden for 68.8% of biopsies and 83.0% of frozen sections, and defer 44.5% of IHC stain orders, with PPVs of 1.0, 0.991, and 0.966. Beyond prospective validation, we conducted a crossover RCT with eight pathologists, in which AI assistance improved diagnostic accuracy across 4,928 case-reader pairs (91.7% w/ AI vs. 83.8% w/o AI). AI assistance also reduced median diagnostic time by 19.6%, increased diagnostic confidence by 8.7%, and improved inter-rater agreement from moderate (kappa = 0.56) to substantial (kappa = 0.76). Together, these evaluations support PulmoFoundation as a clinically validated decision-support system for lung pathology.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Conventional computed tomography (CT) imaging, while essential for detection and staging, has limitations in distinguishing benign from malignant lesions and providing interpretable diagnostic insights. To address this challenge, this study proposes a dual-modal artificial intelligence framework that integrates CT radiology with hematoxylin and eosin (H&E) histopathology for lung cancer diagnosis and subtype classification. The system employs convolutional neural networks to extract radiologic and histopathologic features and incorporates clinical metadata to improve robustness. Predictions from both modalities are fused using a weighted decision-level integration mechanism to classify adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell lung cancer, and normal tissue. Explainable AI techniques including Grad-CAM, Grad-CAM++, Integrated Gradients, Occlusion, Saliency Maps, and SmoothGrad are applied to provide visual interpretability. Experimental results show strong performance with accuracy up to 0.87, AUROC above 0.97, and macro F1-score of 0.88. Grad-CAM++ achieved the highest faithfulness and localization accuracy, demonstrating strong correspondence with expert-annotated tumor regions. These results indicate that multimodal fusion of radiology and histopathology can improve diagnostic performance while maintaining model transparency, suggesting potential for future clinical decision support systems in precision oncology.

Information extraction from pathology reports is essential for cancer staging, tumor registry population. Yet key data remains embedded in narrative reports, making manual extraction labor-intensive and error-prone. Traditional supervised Natural Language Processing pipelines address this through fully supervised Named Entity Recognition and Relation Extraction, but require expensive manual annotation and suffer cascading failures when upstream entities are missed. In this study, we developed a zero-shot, agentic workflow, and evaluated five open-source generative Large Language Models (LLMs) to populate 13 College of American Pathologists synoptic fields from lung resection pathology reports. We compared them against a state-of-the-art supervised GatorTron NER-RE baseline using a novel, registry-aligned evaluation framework. The baseline achieved Micro-F1of 0.960, while the best zero-shot model (GPT-OSS-20B) achieved Micro-F1 of 0.893 (recall: 0.949), accurately extracting complex relations like Pathologic Stage without task-specific training. These results suggest that open-source, zero-shot agentic LLMs show great potential as a low-cost solution for extracting lung pathology information.