[10] HCC transitions from an early solitary nodule to multifocal intrahepatic spread associated or not with vascular invasion and/or extrahepatic dissemination to lymph nodes and other organs. This evolutionary profile is similar to that of other solid tumors that may progress, affecting the organ of primary origin or spread beyond it. This different tumor stage during the evolution is the backbone of the BCLC model[10] that has been widely endorsed for HCC patient
stratification Roxadustat and treatment allocation.[2, 16, 17] Our data reinforce the prognostic value of the baseline parameters of the BCLC model in patients under systemic treatment. Not unexpectedly, we saw the need to also consider the evolutionary events such as severe liver function impairment and definitive sorafenib interruption as predictors of poorer OS. However, the major novelty relies on the demonstration that the radiologic progression pattern should also be taken into account for prognostic
assessment. This is so, even in patients already BCLC-C at baseline. As shown in Fig. 4, survival of BCLC C patients after imaging progression is significantly different according to the absence or presence of NEH. Thus, while the BCLC stage retains its value, it is necessary to refine the BCLC definitions at the time of radiologic progression in order to properly predict the prognosis of patients still fit to enter into second-line studies because of preserved liver function (Child-Pugh A) and preserved PS (0-1). This “BCLC upon progression” (BCLCp) proposal (Fig. 5) defines as BCLCp-B those patients who present
radiologic progression due buy CHIR-99021 to growth of existing nodules ≥20% or new Belinostat clinical trial intrahepatic sites, but are still within BCLC-B because of the absence of vascular invasion or extrahepatic spread or cancer related symptoms (PS 0). By contrast, those patients who present radiologic progression and evolve to BCLC-C or progress within BCLC-C are divided at the time of progression into BCLCp-C1 (growth of existing nodules ≥20% or new intrahepatic sites) and BCLCp-C2: (progression due to new extrahepatic lesion and/or vascular invasion). We decided to focus our interest on patients with at least one imaging evaluation because these are the patients who are considered for second-line trials. For this reason, the PPS analysis had to exclude the 23 patients without image follow-up. Patients to be considered for second-line trials are a selected population that is not well characterized. They may present a more indolent disease evolution that is not associated with an impaired PS or deteriorated liver function. Our data show that progression pattern is a major determinant of PPS. Thus, if pattern of progression is not considered in trial design and evaluation, the results of second-line trials with a survival endpoint may be flawed. It could be argued that clinical progression due to liver failure may be due to cancer progression that has not been detected by radiology.