Liver tumor imaging staging: a multi-institutional study of a preoperative staging tool for hepatocellular carcinoma

Background & aims The current staging system has limitations in preoperatively assessing hepatocellular carcinoma (HCC) and in precise detailed treatment allocation. This study aims to propose a new Liver Tumor Imaging Staging (LTIS) method for HCC. Methods 1295 patients who underwent CT or MRI and curative liver resection during January 2012 and October 2020 were retrospectively recruited from three independent institutions. All images were interpreted by two abdominal and a board-certified radiologist. LTIS was designed to discriminate low-grade (absence of microvascular invasion [MVI] and Edmondson-Steiner grade III/IV), intermediate (MVI + or Edmondson-Steiner grade III/IV but not both) and high-grade HCC (MVI + and Edmondson-Steiner grade III/IV) upon CT and MRI. Model was constructed in 578 derivation cohort (center 1) and validated in internal center 1 test cohort (n = 291), and external center 2 (n = 226) and center 3 (n = 200), respectively. Cronbach's alpha statistics were determined to assess interobserver agreement. Net clinical benefit of LTIS on recurrence-free survival (RFS) and overall survival (OS) was analyzed with a Cox proportional hazards model. Results LTIS shows good inter-reader agreements in both CT and MRI datasets, with a Cronbach's alpha coefficient of 0.86 and 0.85, respectively. In independent test, LTIS achieved agreement of 73.2% (281/384), 18.9% (100/528), and 69.2% (265/383) for determining low, intermediate, and high-grade HCCs with "ground truth" results. In the Cox analysis, LTIS was comparable to "ground truth" grade for predicting RFS (hazards ratio (HR), 1.30 vs. ground truth grade, 1.36 and 1.56) and OS (HR, 1.76 vs. ground truth grade, 2.00 and 3.03) of patients after surgery. In patients conventionally classified as having low-grade tumors (serum alpha-fetoprotein < 400 ng/mL, stage T1), 47.4% and 35.6% were reclassified as high-grade tumors upon LTIS restaging. The resulting LTIS subgroups showed a significant difference in RFS and OS at Kaplan-Meier analysis (Log-rank test, p < 0.001). Conclusion LTIS provides a potential noninvasive way to precisely stage HCC using CT and MRI.