Bridging and Downstaging Loco-Regional Therapy for Hepatocellular Carcinoma: Tumor Necrosis and Post-Transplant Recurrences

To evaluate the efficacy of loco-regional therapy (LRT) in hepatocellular carcinoma (HCC) by tumor necrosis in explants and predicting factors for HCC recurrences

Materials and Methods:

Retrospective analysis performed on consecutive patients treated with LRT for within and outside of Milan HCC prior to liver transplantation (LT) over 10-years. Categorical and continuous variables analyzed using One-Way ANOVA test, while association of continuous variables assessed with correlation analysis. Linear regression employed for predictor variables. Survival computed with the Kaplan-Meier method and log-rank test. A multivariate regression analysis was conducted to evaluate the recurrence.

Results:

159 patients with HCC treated with 226 LRT sessions (median 1, range 1-5) prior to undergoing LT; 121 within Milan and 38 (23.9%) downstaged outside Milan. The overall explant tumor necrosis after liver transplant was 70.2% (60% in within Milan vs. 80% in downstaged (p >0.05)). The overall tumor necrosis with TACE/MWA, Y90, MWA and TACE were 90.5, 89.3, 85.4 and 70.0% (p< 0.05). The recurrence-free survival rates for patients treated with TACE/MWA and Y90 were both ≥90% (p=0.038). Recurrence of HCC occurred in 12 patients (7.5%) over median follow-up of 11.5 months (range 4-52). Within Milan with bridging LRTs, 5 out of 121 (4.1%) experienced recurrence, while outside of Milan with downstaging LRTs, 7 out of 38 patients (18.4%) developed recurrences; all 7 treated by TACE. Out of 12 recurrences, 1 had 100% necrosis, 4 had ≥90% necrosis, 4 had 50-89% necrosis and 3 had < 50% necrosis in explants. Outside of Milan down-staged, pre-transplant AFP and vascular invasion in explants were significantly and independently associated with recurrence (p=0.04, p=0.004 and p=0.02).

Conclusion:

Bridging and downstaging LRTs resulted in overall pathologic tumor necrosis of 70.2%. Downstaging LRTs resulted in overall tumor necrosis of 80.0% in explants. Recurrence-free survival rates post-LT in patients treated with TACE/MWA and Y90 were ≥90%. Outside of Milan down-staged, AFP and vascular invasion were significantly and independently correlated with tumor recurrence.