Letter: Tumour Burden Score for Predicting Extrahepatic Metastasis in Hepatocellular Carcinoma After Curative Resection

We read with great interest the study by Pinto et al. [1], which evaluated the tumour burden score (TBS) as an independent predictor of extrahepatic progression (EHP) in patients with hepatocellular carcinoma (HCC) following therapy with transarterial chemoembolization (TACE). They retrospectively enrolled 890 TACE-treated patients, determined the optimal TBS cut-off value as 3.66, and further assessed the impact of different TBS subgroups on patient outcomes. Their findings indicated that the risk of post-TACE EHP was significantly higher in the high-TBS group than in the low-TBS group, and combining TBS with alpha-fetoprotein (AFP) enabled accurate discrimination of patients based on their EHP risk. Hepatectomy remains a primary curative modality for HCC, and postoperative metastasis and recurrence are key factors limiting patients' long-term survival. Whether TBS can be extended to predict extrahepatic metastasis and survival in patients with HCC following hepatectomy remains unclear. Therefore, we analysed data from 2528 HCC patients who underwent curative hepatectomy [2] at six medical centres within the GUIDANCE multicentre database (January 2019–January 2025). Given the heterogeneity between patients receiving palliative treatment and those undergoing curative resection, we applied the original TBS calculation logic (maximum tumour diameter in cm and preoperative imaging-documented tumour count [3]) and redefined the optimal TBS cut-off value for our cohort as 4.81 using X-tile software. After a median follow-up of 38.1 months (interquartile range, 19.8–56.9 months), recurrence-free and overall survival were significantly shorter in the high-TBS group (TBS > 4.81) than in the low-TBS group (Figure 1A,B, log-rank test, both p < 0.001). The 5-year cumulative risk of extrahepatic metastasis was 21.3% in the high-TBS group versus 9.3% in the low-TBS group (Figure 1C, p < 0.001). Consistent with Pinto et al.'s study, we integrated TBS with AFP to construct a combined score, which also effectively stratified extrahepatic metastasis risk in patients following curative hepatectomy (Figure 1D). These results demonstrate that TBS may not be limited to patients receiving palliative TACE, but rather serves as a universal tumour burden quantification tool for metastasis prediction across different HCC treatment scenarios. Currently, several large studies [4-7] have demonstrated that the ‘TACE + targeted therapy + immunotherapy’ triple combination regimen confers significantly greater clinical benefits than TACE monotherapy in patients with unresectable HCC. However, tools for the accurate prediction of EHP in those receiving this triple combination regimen remain lacking; thus, TBS alone or in combination with AFP may serve as a valuable prognostic tool to guide clinical decision-making. On the other hand, adjuvant therapy for HCC following curative resection remains an unmet clinical need. Large randomised controlled trials such as STORM [8], IMBrave050 [9] and KEYNOTE937 [10] have failed to confirm a survival benefit with adjuvant therapy. Future studies on precision-stratified adjuvant therapy based on the TBS-AFP combined score may help mitigate the one-size-fits-all dilemma in current postoperative management. Overall, Pinto et al. have conducted a valuable study establishing TBS as a prognostic predictor for HCC patients undergoing TACE. We anticipate further investigations to validate and expand TBS's role in personalised HCC care. Jia-Yong Su: writing – original draft, writing – review and editing. Qiu-Jian Qin: writing – original draft, data curation. Jian-Yuan Meng: writing – original draft, data curation. Zhi-Hao Huang: writing – original draft. Lei-Po Lin: writing – original draft. Zhen Liu: data curation, resources. Shao-Ping Liu: data curation, resources. Xiao-Ling Xu: data curation, resources. Fan-Chao Sha: data curation. Huan Chen: data curation. Qin-Fang Ning: software. Jian-Xu Xie: visualization. Xiao-Tian Xu: data curation. Jia-Yun Chen: data curation. Jian-Hong Zhong: conceptualization, writing – review and editing. Liang Ma: writing – review and editing, resources, data curation. The authors have nothing to report. This work was supported by the Innovation Project of Guangxi Medical University, the Clinical Discipline Construction Project of Guangxi Medical University (Grant GXMULJZ202403) and the First-Class Discipline Innovation-Driven Talent Program of Guangxi Medical University. The authors declare no conflicts of interest. This article is linked Pinto et al. paper. To view these articles, visit https://doi.org/10.1111/apt.70534 and https://doi.org/10.1111/apt.70589. All available data are included in the article. Additional original data can be obtained from the corresponding authors in accordance with privacy/ethical restrictions.