ASAP score may predict HCC recurrence after complete radiological response to locoregional treatments

Background & Aims Alpha fetoprotein (AFP) and prothrombin induced by vitamin K absence/antagonist II (PIVKA-II) are biomarkers for hepatocellular carcinoma (HCC), which have been extensively in the diagnosis of HCC, while their use in the prognosis prediction remains poorly assessed. Recently, a new algorithm (ASAP) - including age, gender, AFP and PIVKA-II - has been validated as an alternative to GALAD for prediction of HCC development with a cut-off of 0.52. The identification of predictors of HCC recurrence after curative treatment has always been relevant to patients’ management, and now may have further utility with the arrival of adjuvant therapies.The aim of our study was to evaluate the predictive role of AFP and PIVKA-II alone or combined in the ASAP score for HCC recurrence in patients who achieved a complete response (CR) after locoregional treatment. Methods In this single-center, observational ongoing study, we have enrolled 156 consecutive patients with first diagnosis of HCC treated by ablation (MWTA) or chemoembolization (TACE). CR was evaluated by CT-scan 1 month after treatment, afterwards patients were evaluated every three months by CT-scan, clinical and biochemical features until recurrence, death or last follow up. PIVKA-II and AFP levels were measured at the day of treatment by Fujirebio assays, Japan. Results 81 (52%) patients with HCC who achieved CR after the first treatment were included: median age 66 (40-87); 83% men, 57% HCV-positive, 91% Child-Pugh A, 85% BCLC 0/A, 53% MWTA. The day of treatment, the median AFP was 6.3 ng/mL (1.3-3,537), median PIVKA-II was 112 (16-5,090) mAU/mL, median ASAP score was 0.405 (-3.44-6.64; 47% with ASAP value > 0.52). During follow up, HCC recurred in 47 (58%) patients [median time to recurrence was 298 (41-1256) days after achieving CR]. PIVKA-II [HR 2.53 (95%CI 1.47-4.35), p=0.001] and age [HR 1.03 (95%CI 1.00-1.07), p=0.013] were the only independent predictors of overall HCC recurrence by a multivariable model for single variables only, while the ASAP score [HR 1.31 (95%CI 1.12-1.52), p<0.001] was the only independent predictor of recurrence in a multivariable model including only scores and algorithms. PIVKA-II [HR 2.14 (95%CI 1.09-4.18), p=0.026] was the only independent predictor of early recurrence in the first multivariable model, while platelet to lymphocyte ratio [PLR; HR 1.02 (95%CI 1.00-1.04)] and ASAP score [HR 1.30 (95%CI 1.03-1.64)] were independent predictors of early recurrence according to the second model. Adopting the ASAP cut-off of 0.52, the algorithm independently predicted HCC recurrence [HR 3.54 (95%CI 1.86-9.75), p<0.001], but did not predict HCC early recurrence [HR 1.95 (95%CI 0.87-4.34), p=0.103]. Conclusions The ASAP algorithm may accurately predict HCC recurrence and early recurrence after complete radiological response, deserving further studies to refine the model.