LAUSR

BACKGROUND AND AIMS Following liver resection(LR) for hepatocellular carcinoma(HCC), the likelihood of survival is dynamic, in that multiple recurrences and/or metastases are possible, each having variable impact on outcomes. We sought to evaluate the natural progression, pattern, and timing of various disease states after LR for HCC using multistate modeling and to create a practical calculator to provide prognostic information for patients and clinicians. APPROACH AND RESULTS Adult patients undergoing LR for HCC between Jan-2000 and Dec-2018 were retrospectively identified at a single center. Multistate analysis modeled post-LR tumour progression by describing transitions between distinct disease states. In this model, the states included surgery, intra-hepatic recurrence(1st ,2nd ,3rd ,4th ,5th ), distant metastasis with or without intra-hepatic recurrence, and death. Of the 486 patients included,169(34.8%) remained recurrence-free,205(42.2%) developed intra-hepatic recurrence, 80(16.5%) developed distant metastasis, and 32(7%) died. For an average patient having undergone LR,there was a 33.1% chance of remaining disease-free,31.0% of at least one intra-hepatic recurrence,16.3% of distant metastasis, and 19.8% of death within the first 60-months post-LR. The transition probability from surgery to first intra-hepatic recurrence, without a subsequent state transition, increased from 3%(3-months),to 17.4%(30-months),and 17.2%(60-months). Factors that could modify these probabilities included tumour size, satellite lesions, and microvascular invasion. CONCLUSIONS In contrast to standard single time-to-event estimates, multistate modeling provides more realistic prognostication of outcomes after LR for HCC by taking into account many postoperative disease states and transitions between them. Our multistate modeling calculator can provide meaningful data to guide the management of patients undergoing postoperative surveillance and therapy.