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Accurate esophageal cancer staging relies on ¹⁸F fluorodeoxyglucose positron emission tomography (¹⁸F FDG-PET), but its interpretation is complex and time-intensive. This diagnostic burden is exacerbated by significant workforce shortages in both radiology and surgery, thus necessitating automated support systems. The emergence of advanced large language models (LLMs) has raised expectations for their potential to fulfill this role in complex medical tasks.

We evaluated the diagnostic accuracy of LLMs for staging esophageal cancer using ¹⁸F FDG-PET images, with a focus on their ability to assess lymph nodes (LNs; clinical N [cN]) and distant metastases (clinical M [cM]) for automated radiology reporting.

This retrospective study included 120 consecutive adult patients who were diagnosed with esophageal squamous cell carcinoma and underwent ¹⁸F FDG-PET/computed tomography at Tohoku University Hospital between January 2019 and December 2021. Patients with prior treatment, nonsquamous cell carcinoma histology, or blood glucose levels ≥200 mg/dL were excluded. Frontal maximum-intensity projection positron emission tomography images were extracted, standardized, and analyzed along with information regarding the tumor location. Six LLMs (GPT-5, GPT-4.5, GPT-4.1, OpenAI-o3, -o1, and GPT-4 Turbo) and 4 blinded human evaluators (a nuclear medicine specialist, a gastrointestinal surgeon, and 2 radiology residents) assessed the presence of thoracic and abdominal LN metastases on a region-level basis and determined cN and cM staging on a patient-level basis. The model analyses were performed using the application programming interface in a zero-shot setting. Radiology reports served as the reference standard. Diagnostic agreement and accuracy were evaluated using Cohen κ and the Cochran Q test. Additionally, to account for the class imbalance in the dataset, the Matthews Correlation Coefficient was calculated as a robust metric for binary classification performance. Post hoc McNemar tests were performed with Bonferroni correction; statistical significance for pairwise comparisons was set at P<.0083 (adjusted from P<.05) using JMP Pro (version 18.0; SAS Institute Inc).

The average accuracy was 41/120 (34%) to 94/120 (78%) for LLMs and 72/120 (60%) to 102/120 (85%) for physicians, with significantly higher accuracy for physicians (P<.05) in the thoracic LN, abdominal LN, and cN stages. Interrater reliability was slight to fair for LLMs (κ: -0.07 to 0.25) and fair to substantial for physicians (κ: 0.27 to 0.74). Matthews Correlation Coefficient scores were consistently higher for physicians (0.28 to 0.75) than for LLMs (-0.07 to 0.32). Among the LLMs, GPT-5 demonstrated the highest overall accuracy, with newer LLMs showing improved diagnostic accuracy when compared with previous models in identifying abdominal LN metastases and cM staging, though they showed weaker consistency for cN staging. For example, in thoracic LN detection, GPT-5 achieved 76/120 (63%) accuracy, whereas other LLMs achieved 72/120 (60%) or lower accuracy.

Although current LLMs have not yet reached physician-level accuracy in comprehensive staging, recent models show promise in assisting with specific diagnostic tasks.