Optimal duration of adjuvant targeted-immunotherapy in patients with initially unresectable hepatocellular carcinoma with portal vein tumor thrombus following successful conversion therapy

BACKGROUND: The management of initially unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has been revolutionized by conversion therapy combining locoregional and systemic modalities. While successful downstaging followed by salvage surgery offers potential for cure, the optimal duration of postoperative adjuvant targeted-immunotherapy remains poorly defined. This multicenter study aimed to determine the relationship between adjuvant therapy duration and survival outcomes in this specific patient population. METHODS: We conducted a retrospective cohort analysis of 124 patients with initially unresectable HCC and PVTT who achieved successful conversion using combined local-systemic therapy and subsequently underwent R0 resection at 4 tertiary medical centers between September 2019 and December 2022. Patients were stratified into 4 groups according to adjuvant targeted-immunotherapy duration: no adjuvant therapy (0 month, n = 26), short-term therapy (1-3 months, n = 28), medium-term therapy (4-6 months, n = 25), and extended therapy (≥7 months, n = 45). Primary endpoints were overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier methods and Cox proportional hazards models. RESULTS: With a median follow-up of 28.3 months, significant differences in both OS and PFS were observed among the 4 groups (both P < .0001). Compared to the no-adjuvant group, all treatment durations showed significant survival benefits, with hazard ratios of 0.49 (P = .004) for OS and 0.44 (P = .010) for PFS in the 1-3 month group, improving to 0.22 (P < .001) for OS and 0.15 (P < .001) for PFS in the 4-6 month group. Critically, the medium-term therapy (4-6 months) demonstrated statistical non-inferiority compared to extended therapy (≥7 months) for both OS (P = .85) and PFS (P = .30), establishing a clear efficacy plateau. Treatment-related adverse events were manageable and comparable across all duration groups. CONCLUSIONS: This study provides compelling evidence that adjuvant targeted-immunotherapy duration significantly impacts survival outcomes in converted unresectable HCC patients with PVTT. The 4-6 months adjuvant regimen represents the optimal therapeutic window, maximizing survival benefits while avoiding unnecessary extended treatment. These findings should inform clinical practice and guide the design of future prospective trials.