Prognostic significance of pathological response in unresectable hepatocellular carcinoma treated with immune checkpoint inhibitor-based conversion therapy.

Abstract

4140 Background: Immune checkpoint inhibitor (ICI)-based conversion treatment is increasingly utilized for patients with initially unresectable hepatocellular carcinoma (HCC). However, standardized histopathologic markers for assessing treatment response and predicting survival outcomes remain inadequately defined. Methods: This retrospective study analyzed 225 HCC patients who underwent conversion treatment followed by curative resection. The residual viable tumor percentage (RVT%) was calculated as the proportion of RVT surface area to the total tumor bed area. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between RVT% and recurrence-free survival (RFS) as well as overall survival (OS). Results: Complete pathologic response (CPR), defined as 0% RVT, was achieved in 60 patients (26.7%) and was strongly associated with improved survival outcomes. Patients with CPR exhibited significantly better RFS (HR: 0.23, 95% confidence interval [CI]: 0.13–0.41, p < 0.001) and OS (HR: 0.17, 95% CI: 0.05–0.56, p = 0.003) compared to non-CPR patients. Multivariate analysis confirmed non-CPR as an independent risk factor for both RFS (HR: 3.67, 95% CI: 1.94–6.96, p < 0.001) and OS (HR: 4.43, 95% CI: 1.21–16.18, p = 0.022). Major pathologic response (MPR), defined as RVT% ≤ 10%, was observed in 91 patients (40.4%) and was also significantly associated with improved RFS and OS (all p < 0.05). Stratification by RVT% thresholds revealed a stepwise association between decreasing RVT% and improved survival outcomes. RVT% ≤ 30% demonstrated significant predictive power for both RFS (HR: 0.48, 95% CI: 0.30–0.75, p = 0.001) and OS (HR: 0.60, 95% CI: 0.31–1.16, p = 0.020). Notably, patients with CPR achieved a two-year survival rate of 96.7%, compared to 86.1% in non-CPR patients. Despite the high radiological response rate (CR+PR, 92.4%), substantial discrepancies were observed between radiological and pathological assessments, and 56.7% of patients who achieved pathological complete response (CPR) did not exhibit radiological complete response (CR). Kaplan-Meier analysis showed no significant differences in RFS or OS among three regimens: anti-PD-1 monotherapy (n = 25, 11.1%), anti-PD-1/PD-L1 plus anti-VEGF (n = 21, 9.3%), and anti-PD-1 plus TKI (n = 179, 79.6%). Transarterial chemoembolization (TACE) did not significantly increase the proportion of patients achieving CPR but notably enhanced the proportion of patients with RVT% ≤ 30%. Conclusions: Both CPR and MPR are robust prognostic markers of RFS and OS in HCC patients undergoing ICI-based conversion treatment. The superior sensitivity of pathological evaluation underscores its advantage over radiological assessment in accurately reflecting treatment outcomes.