Prognostic value of pathological response for patients with unresectable hepatocellular carcinoma undergoing conversion surgery

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aim to explore the prognostic value of pathologic response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy, and identify predictors of major pathologic response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of non-viable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥ 90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR was significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7 % and 19.4%; p <0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3 and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥ 2.6 (p = 0.016) and preoperative alpha-fetoprotein ≥ 400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.