Continuous adjuvant therapy with the same regimen improves survival following conversion therapy and hepatectomy in initially unresectable hepatocellular carcinoma: a multicenter retrospective study

Background: Conversion therapy can provide patients with locally advanced hepatocellular carcinoma (HCC) the opportunity for surgical resection. However, it remains uncertain whether these patients still need to receive adjuvant therapy after hepatectomy. This study aimed to assess the efficacy and safety of continuous adjuvant therapy using the same regimen following conversion systemic therapy and hepatectomy in patients with initially unresectable HCC.

Methods: Between October 2019 and October 2023, patients diagnosed with unresectable HCC who underwent conversion therapy and subsequently received hepatectomy were retrospectively enrolled. The cohort was divided based on whether they received adjuvant therapy with the same regimen as used in conversion therapy (Adj group) or not (Non-Adj group). The primary endpoint was recurrence-free survival (RFS). The secondary endpoints were overall survival (OS) and safety.

Results: A total of 158 patients received conversion therapy without adjuvant therapy after hepatectomy (Non-Adj group), and 117 patients received continuous adjuvant therapy with the same regimen after conversion therapy and hepatectomy (Adj group). The 1- and 2-year RFS rates in the Non-Adj and Adj groups were 44.3%, 34.2%, and 76.1%, 68.4%, respectively [hazard ratio (HR) =0.34, P<0.001]. The 1-, 2- and 3-year OS rates in the Non-Adj and Adj groups were 87.3%, 77.2%, 74.7%, and 95.7%, 90.6%, 88%, respectively (HR =0.46, P=0.009). Subgroup analyses identified that patients exhibiting objective tumor responses to conversion therapy could benefit more from sequential adjuvant therapy compared to non-responders (P<0.001 for RFS and P=0.008 for OS). Multivariable analyses confirmed adjuvant therapy as independent prognostic factors for RFS (P<0.001) and OS (P=0.002). Adverse events were manageable and tolerable in both groups.

Conclusions: Continuing adjuvant therapy with the same regimen after conversion therapy and hepatectomy significantly improved survival outcomes in patients with initially unresectable HCC. The findings emphasize the importance of maintaining the same therapy protocol postoperatively for this patient population.