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To TACE or not to TACE: that is the question

Transarterial chemoembolization (TACE) is the treatment of choice for patients with intermediate stage hepatocellular carcinoma (HCC), classified according to the Barcelona Clinic Liver Cancer staging system (BCLC B) (1). For a standard treatment, there is a remarkable degree of heterogeneity in the type of patients who undergo TACE in the method of administration and in the frequency and timing of the procedure. The classical patient is one whose liver function is no worse than Child B7, good performance status and who is unable to have surgery for any of a number of different reasons. These may include comorbid diseases, tumour extent, number and location. In addition, the lesions have to be large enough to preclude radiofrequency ablation. Patients with otherwise resectable lesions who have portal hypertension that precludes surgery may also be offered TACE. Similarly, patients with lesions that are not anatomically resectable despite absence of portal hypertension and even with preserved liver function are also offered TACE. TACE candidates may have a single lesion or multiple lesions. In addition, patients with BCLC stage A disease who have undergone prior treatment that has failed are also eligible for TACE. It is obvious therefore that standard indications for TACE allow a largely heterogeneous group of patients to be treated by the same method. In carefully selected patients, the median survival following TACE is more than 2 years, with prolonged survival documented (2, 3). Given the heterogeneity of the patient population, it is difficult to accurately assess what the prognosis might be for an individual patient. It is not surprising therefore that investigators would attempt to impose some rigour to the assessment of post-TACE prognosis. There have been several attempts to do so. One of the first was the assessment for retreatment with TACE (ART) score (4), consisting of albumin, bilirubin and tumour size. This score was intended to determine whether a second TACE procedure should be performed, or whether the prognosis was so poor that TACE was unlikely to prolong life significantly. The ART score was based on data collected just prior to the second TACE. Survival was assessed after the second TACE. The ART score therefore reflected the post-second TACE prognosis. Shortly thereafter, the HAP score (5) was described. This score was intended to predict the outcome of TACE using data prior to the first TACE. Modified HAP (mHAP), a modified version of hepatoma arterialization protocol (HAP) (6), included the variables from HAP, and added post-treatment radiologic response to TACE. This meant that it could only be used retrospectively, and not prior to the first TACE. Another modification, mHAP-II (7), used a similar set of variables, including albumin, bilirubin, alpha-foetoprotein and tumour size and number, and did not require an assessment of response to TACE. The variables were stratified as categorical variables, rather than continuous variables. In this edition of the journal, Cappelli et al. (8) describe yet another variation on the theme, by developing a scoring system that includes the same variables as mHAP-II, but used as continuous variables. They were able to develop a formula, now available on the web, to calculate the median survival that could be applied to individual patients using data from before the first TACE. They show that this score is superior to existing comparable scores, the HAP score and the mHAP-II score based on C statistics and the Akaike Information Criterion (The C statistic reflects differences in the area under the Receiver Operating Characteristic curve, and the Akaike information Criterion is an estimate of the quality of the different models being considered). The current model (mHAP-III) includes albumin, bilirubin and alpha-foetoprotein as variables in addition to tumour size and number. The inclusion of variables as continuous variables rather than categorical variables (except for tumour number) improves the accuracy of the model since stratifying data into categories is associated with loss of information. Patients with portal vein tumour thrombus were excluded. Some of the previous scores included