EndoGov: A knowledge-governed multi-agent expert system for endometrial cancer risk stratification

Abstract

Multimodal artificial intelligence models for endometrial cancer (EC) risk stratification typically optimize aggregate predictive performance but provide limited mechanisms for enforcing mandatory guideline overrides, such as assigning POLE-mutated tumors to the low-risk group despite high-grade morphology. We present EndoGov, a two-tier multi-agent expert system that factorizes the decision process as D(x) = G(P(x), R), where specialist agents P extract structured evidence and a governance agent G applies an executable rule set R. Tier 1 comprises pathology, molecular, and clinical agents that independently generate schema-constrained reports from frozen foundation-model features or structured records. Tier 2 queries an evidence-level-weighted Guideline Knowledge Graph, using deterministic hard-path rules for high-priority overrides and constrained soft-path reasoning for ambiguous cases. In TCGA-UCEC (n=541), EndoGov achieved 0.943 accuracy, 0.973 macro AUC, and a conditional logic-violation rate (C-LVR) of 0.93% among trigger-exposed cases. In CPTAC-UCEC (n=95), where reference labels are guideline-derived, EndoGov reached 0.842 accuracy compared with < 0.31 for locked-transfer neural baselines, supporting governance-pathway transfer under distribution shift rather than validation against independent clinical truth. End-to-end safety decomposition localized residual failures primarily to upstream molecular detection rather than downstream governance. Backend-swap experiments further showed that hard-path compliance is invariant to the LLM backend. These findings indicate that explicit clinical-rule governance can provide guideline-compliant, auditable EC risk assignment while preserving competitive discrimination.