The Multiparametric Therapeutic Hierarchy (MTH) has been proposed as an evolution of the Barcelona Clinic Liver Cancer (BCLC) algorithm to better reflect the complexity of real-world hepatocellular carcinoma (HCC) management. While the BCLC often assumes idealised conditions, the MTH explicitly incorporates “treatment unfeasibility” as a variable in clinical decision-making, a concept this review seeks to examine and refine. We propose that unfeasibility should not be limited to absolute contraindications but should be understood as a multidimensional construct comprising four interacting dimensions: (1) Technical Feasibility; (2) Resources; (3) Equity; and (4) Values and Acceptability. This concept of unfeasibility adapts the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision (EtD) framework, originally designed for population-level guideline development, to individual-level clinical reasoning. At the point of care, the five EtD domains (Feasibility, Resources, Acceptability, Equity, and Values and Preferences) converge into a unified assessment of treatment feasibility for the specific patient. A precise mapping between our four dimensions and the original GRADE domains is provided. This approach is complementary to, rather than a departure from, GRADE methodology and is particularly relevant in settings characterised by low or very low certainty of evidence. Our analysis reveals a recurring inverse relationship between therapeutic efficacy and feasibility: the most effective treatments, such as liver transplantation, are often constrained by technical, resource-related, and systemic barriers. This tension results in widespread undertreatment across the HCC population. By defining unfeasibility as a key element of expert reasoning, this framework aims to enhance transparency in how multidisciplinary tumour boards weigh multiple considerations when making individualised treatment decisions under uncertainty, without prescribing decision rules or treatment recommendations.

Background/Objectives: Salvage liver transplantation (SLT) is a well-established option for hepatocellular carcinoma (HCC) recurrence after liver resection. Laparoscopic microwave ablation (L-MWA) represents another curative strategy for early-stage HCC. However, its role within this therapeutic framework remains unexplored. Methods: Between 2014 and 2023, we treated 1341 patients with HCC using L-MWA. From this cohort, patients with Child-Pugh class A liver function, HCC within the Milan criteria, no contraindications to transplantation, and ≥12 months of follow-up were selected. SLT failure was defined as non-transplantable recurrence or death, resulting in the loss of a potentially curative therapeutic opportunity. The primary endpoint was overall survival (OS); secondary endpoints included predictors of survival and SLT failure. Results: A total of 341 patients met the inclusion criteria. Five-year OS was 62%. Independent predictors of poorer survival included the presence of cardiac disease or oesophageal varices, a Child-Pugh score of 6, tumour size, and elevated alpha-fetoprotein (AFP) levels. Treatment was successful in 255 patients (74.8%): 102 (29.9%) underwent SLT, 67 (19.6%) received alternative therapies, and 93 (27.3%) remained recurrence-free. Treatment failure occurred in 86 patients (25.2%) due to non-transplantable recurrence or death. Independent predictors of failure included older age, non-HBV aetiology, and elevated AFP levels. Five-year OS rates were 79% in the success group and 22% in the failure group (p < 0.001). Conclusions: A combined L-MWA and SLT strategy is safe and effective, yielding a 62% 5-year OS rate. This approach supports more efficient graft use with a consequent increase in the population transplant benefit. Improved selection may further reduce failure rates.