A multicenter retrospective study has demonstrated the potential of tislelizumab as an effective adjuvant therapy for preventing recurrence in hepatocellular carcinoma (HCC) patients at high risk following curative resection. The research, conducted across six hospitals in China, provides new evidence for immunotherapy's role in post-surgical HCC management.
Study Design and Patient Population
The study analyzed 108 patients who underwent curative liver resection for HCC between June 2020 and January 2024. All patients had at least one high-risk factor for recurrence, including tumor size greater than 5 cm, multinodular tumors, macrovascular or microvascular invasion, poor differentiation (Edmondson-Steiner grade III-IV), or satellite lesions.
Among the study population, 85.2% had chronic hepatitis B virus etiology and 72.2% presented with liver cirrhosis. Elevated serum alpha-fetoprotein levels were found in 67.6% of patients, while microvascular invasion was detected in 59.3% of cases.
Treatment Protocols and Efficacy Results
Patients received tislelizumab (200mg intravenously every 3 weeks) either as monotherapy (43 patients, 39.8%) or in combination with tyrosine kinase inhibitors (65 patients, 60.2%). The TKIs used included lenvatinib, donafenib, sorafenib, anlotinib, and apatinib.
With a median follow-up of 24.3 months, the study achieved impressive recurrence-free survival rates. The RFS rates at 6, 12, and 24 months were 89.8%, 71.3%, and 59.3%, respectively. Overall survival rates reached 88.0% at 12 months and 83.4% at 24 months. Neither median RFS nor OS was reached during the observation period.
Duration of Treatment Impact
A key finding emerged regarding treatment duration. Patients who received adjuvant therapy for at least 6 months demonstrated significantly longer RFS compared to those treated for less than 6 months (p=0.020, HR 2.29, 95%CI 1.14-4.61). However, landmark analysis revealed that the survival benefit was primarily confined to the initial 12-month follow-up period.
Monotherapy Versus Combination Therapy
Contrary to expectations, the addition of TKIs to tislelizumab did not provide additional survival benefit. The median RFS showed no significant difference between tislelizumab monotherapy and combination therapy (HR 1.46, 95%CI 0.58-1.90). Similarly, overall survival showed no significant difference between groups (HR 1.06, 95%CI 0.42-2.67).
Safety Profile Analysis
The safety analysis revealed important differences between treatment approaches. The incidence of treatment-related adverse events (TRAEs) was significantly higher in the combination group compared to monotherapy (89.2% vs 65.1%, p=0.003). Grade 3 or higher TRAEs occurred in 38.5% of combination therapy patients versus 18.6% in the monotherapy group.
The most frequently reported TRAEs in both groups were elevated aspartate aminotransferase and alanine aminotransferase levels, occurring in 37.2% and 47.7% of patients respectively. The combination group experienced significantly higher rates of hypertension, decreased appetite, weight loss, diarrhea, and joint pains or myalgia.
Treatment modifications were required more frequently in the combination group, with 33.8% of patients experiencing TRAEs leading to treatment modifications compared to 16.3% in the monotherapy group. No treatment-related deaths occurred in either group.
Clinical Implications
The researchers noted that in patients who have undergone curative surgery for HCC, the body is already in a tumor-free state, which may explain why the addition of TKIs did not significantly improve outcomes. TKIs primarily work by inhibiting abnormally activated tyrosine kinases in proliferating tumor cells, but their benefit may be limited in the post-surgical setting.
The study's findings are particularly significant given that HCC represents the sixth most commonly diagnosed malignancy worldwide and the third leading cause of cancer-associated deaths. Despite curative resection, the 5-year recurrence rate can reach up to 70%, making effective adjuvant therapy crucial for improving long-term survival.
Study Limitations and Future Directions
The researchers acknowledged several limitations, including the retrospective nature of the study, relatively small sample size, and short follow-up duration. They emphasized the need for prospective randomized controlled trials with larger patient populations to validate these findings and determine the optimal duration of adjuvant immunotherapy.
The study suggests that tislelizumab monotherapy for at least 6 months may represent the optimal adjuvant approach for high-risk HCC patients, offering a favorable balance between efficacy and toxicity while potentially reducing treatment costs compared to combination therapy.
