ARTEMIS: a pilot study comparing AI-based and expert therapeutic decisions in simulated clinical cases of neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) are rare and heterogeneous malignancies requiring multidisciplinary management. Large language models (LLMs) are emerging as decision-support tools, but their role in therapeutic decision-making is largely unexplored. ARTEMIS was a pilot cross-sectional study comparing three configurations—a baseline GPT, a customised GPT with static domain knowledge (GPTs), and a retrieval-augmented GPT (RAG)—against a panel of nine Italian NEN experts using twenty simulated, non-surgical cases. The primary endpoint was non-inferiority for systemic therapy recommendations; secondary endpoints included completeness, explicit uncertainty, parsimony of additional tests, costs, and variability metrics. RAG and GPTs achieved 70.0% agreement versus the expert benchmark (63.8%), meeting the exploratory –10% non-inferiority margin but not the stricter –5% threshold. Baseline GPT reached 60.0% and was not non-inferior. All AI systems consistently produced complete recommendations and expressed uncertainty more often than experts; RAG tended to propose fewer additional tests and lower associated costs. Experts showed greater variability than AI systems, and Ki-67 correlated with disagreement, indicating biological aggressiveness as a source of uncertainty. This exploratory study suggests that LLMs can approximate expert therapeutic reasoning under controlled conditions, but concordance remains limited and external validation in real-world settings is needed before clinical use.