Sustained Complete Response after Biological Downstaging in Patients with Hepatocellular Carcinoma: XXL-Like...

The XXL trial represents the first prospective validation of "biological downstaging" in liver transplantation (LT) for hepatocellular carcinoma. The aim of this study was to compare the Padua downstaging protocol to the XXL protocol in terms of downstaging failure rates and patient outcome. A total of 191 patients undergoing aggressive surgical downstaging and potentially eligible for LT from 2012 to 2018 at our center were retrospectively selected according to XXL trial criteria. Unlike the XXL trial, patients with a complete response to downstaging did not receive any prioritization for LT. Downstaging failure was defined as stable progressive disease or post-treatment mortality. The statistical method of "matching-adjusted indirect comparison" was used to match the study group to the XXL population. Downstaging failure rate was considerably lower in the study group than in the XXL trial (12% vs. 32%, d value = |0.683|). The survival curves of our LT group (n = 68) overlapped with those of the LT-XXL group (p = 0.846). Survival curves of non-LT candidates with a sustained complete response (n = 64) were similar to those of transplanted patients (p = 0.281). Our study represents a validation of the current Padua and Italian policies of denying rapid prioritization to patients with complete response to downstaging. Such a policy seems to spare organs without worsening patient outcome.