Need for independence of treatment allocation from prognostic evaluation for hepatocellular carcinoma

The complexity of the evaluation patients with hepatocellular carcinoma (HCC) is related to need simultaneously considering – when planning treatment and assessing prognosis not only magnitude tumour burden degree general well-being (i.e. their Performance Status [PS]) as in other malignancies, but also extent concomitant liver dysfunction. Moreover, adding further complications difficulties faced streamlining this complex process, various evidence-based treatments are available treat HCC. This has led, through years, development several, variously designed prognostic scores staging systems, without having yet reached a consensus on universally accepted best one. HCC assessment can be divided into two main categories, differing design characteristics (data based or evidence based), value, significance allocation.1 Evidence-based systems (Tumour Nodes Metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC] Chinese [CNLC] classifications) defined patients' from literature typically offer linkage, sometimes univocal, modalities. Data-based (Okuda system, Italian Program [CLIP] score, Japan Integrated Staging [JIS] Model Estimate Survival for [MESH] score], hand, obtained rigorous statistical methodology demonstrated have better performance compared systems.2 Lastly, third category identified, namely combined used both systems. A recent example one these weighted real population, (ITA.LI.CA) system.3 Hepatocellular Carcinoma Prediction Score (HCC-SPS), proposed by Tan et al. current issue International, categorised data-based score. Indeed, study an interesting how kind created, relying real-life population data, solid bases, internal external validation.4 Noteworthy, HCC-SPS score incorporates multitude parameters comparison survival scores. In addition characteristics, it assesses functional reserve, albumin–bilirubin (ALBI) grade patient's physical status. Furthermore, includes humoral parameter which widely clinical practice assess ‘biological aggressiveness’ HCC, such alpha-fetoprotein.5 One its limits, though, scarce numerosity validation populations. Another limitation that needs derived each single-centre thus requiring presence database being able prognosticate universal rate. clearly marked difference observed overall same risk across cohorts. Its more groups therefore essential confirm applicability. original aspects paper was equally effective including modality, even though showed significant independent factor patient analysis. highlight benefit applicability at moment diagnosis, suggesting definition independently preferable approach prediction outcome.4 Prognostic independence allocation well-established concept concerning malignancies (e.g. Fong's field colorectal metastases), still distinctly HCC.6 regard, manuscript Tang al., using Akaike information criterion values performed than BCLC although, unfortunately, comparisons were possible. last decades, inexplicable anomaly characterised stratification management. claim adopt unique system working classification algorithm. classification, first presented 1999 aim classifying basis therapeutic perspectives.7 As above underlined confirmed al.,4 lower ability determine patients, particular quite heterogeneous classes, Intermediate Advanced one, taken consideration.8, 9 But second relevant consequence ‘BCLC anomaly’ originally presented, rigid ‘stage hierarchy’ uniquely assigned single specific determined stage. It strict undertreat who might instead achieved outcomes if treated flexibly sorted therapies.10 Attempts introduce flexibility introduced European Association Study (EASL) 2018 guidelines ‘treatment stage migration’) American (AASLD) alternative’) management HCC.11, 12 However, attempts do guarantee possibility assign therapy dictated philosophy precision medicine.13 More recently, idea offering whole array order pick fitting individual ‘therapeutic hierarchy’, important concepts.14 First, existence hierarchy effectiveness between different strategies HCC.15 Second, less importantly, separating modality suggested al.4, 16 Thus, fresh start direction application we acknowledge invitation put forward authors studies settings needed