This study first compared TACE and HAIC as initial IAT for pHCC. In previous studies, IAT treatment had been demonstrated to provide survival benefits outperforming the optimized support care for HCC cases [19, 20]. However, outcomes of pHCC with a diameter > 5 cm remained poor [21], which may be attributed to a higher tumor burden. A study compared TACE with HAIC for iHCC and reported that the outcomes of HAIC were superior to TACE [22]. However, this study came to a conclusion that TACE outperformed HAIC for pHCC. Specifically, the OS of the TACE group before PSM was enhanced compared with the HAIC group, while the PFS of the TACE group after PSM was enhanced compared with the HAIC group.
In the present study, the median OS and PFS of TACE for single pHCC (diameter > 5 cm) were 16.8 and 5.8 months, respectively. Duan et al. reported that simultaneous TACE and radiofrequency ablation could be a safe yet effective treatment for large HCC (diameter > 8 cm) [23]. Irie et al. reported a new TACE technique for large HCC nodules (> 7 cm), which included sparse gelatin slurry under balloon occlusion and repeated alternate infusion of cisplatin solution (RAIB-TACE) [24]. Indeed, surgery, ablation and SBRT were excellent local treatments for HCC and suitable for combined treatment with TACE in a sequential manner. Herein, the target was cases with HCC beyond Milan criteria. Therefore, minimization of the tumor burden was the key to improve OS.
The ALBI grade consisted of both bilirubin and serum albumin, which made it a more objective replacement of Child-Pugh class for hepatic function assessment [25, 26]. The multivariate analysis revealed that the AIBI grade is a key predictor for the OS. The changes of ALBI scores showed significant hepatic function deterioration in both groups with consistent deterioration degrees, indicating that changes in liver function had important implications for the survival of pHCC cases. Before and after PSM, both PRR and ORR of the TACE group were enhanced compared with the HAIC group. Indeed, TACE treatment for pHCC resulted in more adequate lipiodol deposition, while HCC with incomplete capsules had poor lipiodol deposition. Vascular embolization combined with chemotherapy could effectively control tumor progression, which might be the main reason why the PRR and ORR of the TACE group were higher than those of the HAIC group. The median PFS of the HAIC and TACE groups after PSM was 2.8 and 5.3 months, respectively (P = 0.003).
As pHCC was morphologically a complete capsule, the TACE procedure could easily block the majority of supply arteries to ensure that chemotherapy drugs can act directly. In Asia, HAIC had been widely employed to handle advanced HCC. FOLFOX using oxaliplatin as combined anti-cancer method has been demonstrated to be an effective treatment for advanced HCC [27–29]. It was speculated that the superior therapeutic effect of TACE for pHCC might be related to the resistance of large HCC to repeated chemotherapy, the increased blood supply of pHCC, and the multiplied effect of embolization combined with chemotherapy. In addition, TACE and HAIC led to lower AE incidence compared to TKIs and systemic chemotherapy. Overall, the safety and effectiveness of TACE for pHCC were validated.
The developed prognostic nomogram model consisted of three pre-treatment variables. The visual model demonstrated good predictive capability, with one-, two- and three-year OS of 0.697, 0.722 and 0.778, respectively, for the validation dataset. Hepatic function and tumor size were recognized as crucial factors for the prediction of survival prognosis. The selective TACE deserved to be recommended for pHCC. With rational efficiency and stability, this nomogram model could generate a prognostic risk score before the IAT treatment, thus providing meaningful guidance for follow-up and subsequent treatments of patients.
This study also has several limitations. First, selection bias was inevitable, although such risk was significantly reduced by total inclusion of consecutive patients with pseudo-capsulated HCC and the use of PSM. Second, this study was retrospective with relatively small sample size. Hence, prospective multi-center studies with a large cohort are needed in the future. Third, no universal evaluation criterion has been established for pHCC. Therefore, there may be imbalance in the inclusive population, leading to bias in the survival outcomes.