Zhijian Cen

Ling Liang, Jiabo Ma, Zhengyu Zhang et al.

Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100% NPV for rule-out and 100% PPV for rule-in, GRACE streamlined review for up to 69.6% of malignancy-diagnosis cases and triaged 46.8% of MMR-IHC follow-up requests. This translational feasibility was further strengthened by a randomized crossover reader study of pathologist-AI collaboration. With GRACE assistance, diagnostic accuracy improved from 82.0% to 89.9%, yielding nearly twofold higher adjusted odds of a correct diagnosis (OR 1.987) alongside concurrent gains in sensitivity and specificity. AI assistance also reduced diagnostic time by 14.9%, elevated diagnostic confidence by 9.0%, and markedly improved inter-rater agreement. When calibrated to maintain non-inferior performance to senior pathologists, the AI-assisted workflow could triage 60.7% of atrophy and 82.7% of intestinal metaplasia cases.

Zhengrui Guo, Zhengyu Zhang, Jiabo Ma et al.

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.

Yingxue Xu, Zhengyu Zhang, Xiuming Zhang et al.

Pathology foundation models have shown strong retrospective performance, but whether such systems can support clinically relevant use remains unclear. This challenge is particularly important in breast cancer, where pathological assessment serves as the gold standard for diagnosis and guides treatment planning, surgical decision-making and risk stratification across pre-, intra- and post-operative stages. Here we present \textbf{BRAVE}, a breast-adaptive pathology foundation model developed and evaluated using a total resource of 101,638 breast whole-slide images from 32 sources across Asia, Europe and North America. We assessed BRAVE across 34 tasks in 82 cohorts spanning pre-operative biopsy, intra-operative frozen section and post-operative resection, using an evidence chain comprising retrospective benchmarking, clinically challenging scenarios, workflow-oriented clinical impact simulations, prospective observational validation with the thresholds locked in the retrospective cohorts and crossover pathologist-AI interaction studies. Across these settings, BRAVE supported practical roles in the clinical workflow, including safe exclusion of low-risk cases from routine review, AI-assisted second-review rescue of initially missed positives and prioritization of cases for further assessment. In prospective validation across three centres, BRAVE excluded 76.9% of negative biopsy cases (NPV 0.953) and 70.1% of negative frozen-section cases (NPV 0.973), and triaged 78.8% of post-operative subtyping cases as high-confidence clear-cut cases (NPV 1.000). In reader studies, AI assistance improved balanced accuracy from 88.5% to 95.1% (OR 3.14, P<0.001), with better efficiency, confidence and inter-rater agreement. BRAVE-derived scores also independently predicted disease-free survival (adjusted HR 4.79, P<0.001) and overall survival (adjusted HR 8.14, P<0.001).