Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection.

ABSTRACT

BACKGROUND & AIMS: Assessment of recurrence risk after liver resection (LR) is critical in hepatocellular carcinoma (HCC), particularly with the advent of effective adjuvant therapy. The aim of this study was to analyze the clinical and pathological factors associated with recurrence, aggressive recurrence, and survival after LR. METHOD: We performed a retrospective study in which all single HCC (BCLC-0/A) patients treated with LR between February 2000 and November 2020 were included. The main clinical variables were recorded. Histological features were blindly evaluated by two independent pathologists. Aggressive recurrence was defined as those that exceeded the Milan criteria at 1st recurrence. RESULTS: A total of 218 patients were included (30% BCLC 0 and 70% BCLC A), median (IQR) tumor size of 28 (19-42 mm). The prevalence of microvascular invasion and/or satellitosis (mVI/S) was 39%, with a kappa-index between both pathologists of 0.8. After a median follow-up of 49 (23-85) months, 61/218 (28%) patients died, 32/218 (15%) underwent liver transplantation, 127 (58%) developed HCC recurrence. The prevalence of aggressive recurrence was 35% (44/127 Milan-out, with 20 cases at advanced stage), and the 5-year survival rate was 81%. The presence of mVI/S was the only independent predictor of recurrence (hazard ratio [HR] 1.83, 95% CI 1.28-2.61, p <0.001), aggressive recurrence (HR 3.31, 95% CI 1.74-6.29, p <0.001) and mortality (HR 2.23, 95% CI 1.27-3.91, p = 0.005). The macrotrabecular-massive subtype was significantly associated with a higher prevalence of mVI/S, Edmonson Steiner grade III-IV, AFP values and vessels that encapsulate tumor clusters, but not with recurrence, aggressive recurrence, or overall survival. CONCLUSION: The presence of mVI/S was the only independent risk factor for aggressive recurrence and mortality. This has important implications for early-stage patient management, especially in the setting of adjuvant immunotherapy or ab initio LT. IMPACT AND IMPLICATIONS Assessment of recurrence risk after liver resection is crucial in patients with hepatocellular carcinoma. Patients with a high risk of recurrence are candidates for liver transplantation as an ab initio indication or for the potential use of adjuvant therapy. Aggressive recurrences, defined as those exceeding the Milan criteria at first recurrence, have a significant impact on overall survival (OS). Fifty-eight percent of patients experienced hepatocellular carcinoma recurrence, with a prevalence of aggressive recurrence at the first occurrence standing at 35%. After a median follow-up of 49 (23-85) months, 61 (28%) patients died, and 32 (15%) underwent liver transplantation, resulting in a 5-year OS rate of 81%. Microvascular invasion and/or satellitosis was present in 39% of our cohort and was the only independent predictor of recurrence, aggressive recurrence, and OS on multivariate analysis. This is important as it could be used to guide therapeutic management.