The Role of Timing of Progression and Early Salvage Surgery in Unresectable Hepatocellular Carcinoma Treated with TACE Plus TKIs and PD‑1 Inhibitors

Abstract

Xingzhi Li,1,2,* Zhihong Tang,1,* Qingqing Pang,1,* Xiaobo Wang,1 Tao Bai,1 Jie Chen,1 Meng Wei,1 Tao Wei,1 Lequn Li,1 Feixiang Wu1,3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Hepatobiliary Surgery, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feixiang Wu; Lequn Li, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China, Email [email protected]; [email protected]: The prognosis of initially unresectable hepatocellular carcinoma (iuHCC) has been improved by TACE with TKIs and PD-1 inhibitors (TTP). However, the role of timing of tumor progression and and early salvage surgery during TTP therapy remains unclear.Patients and Methods: The data of 151 patients who received TTP for iuHCC consecutively between November 2019 and December 2022 were retrospectively analyzed. The X-Tile software was used to determine the optimal threshold of progression timing to differentiate the post-progression survival (PPS) for patients with tumor progression, ultimately yielding 9 months as the optimal cut-off time. Early tumor progression was defined as patients with tumor recurrence (surgical patients) or progressive disease by mRECIST (nonsurgical patients) within 9 months of initial treatment. Accordingly, early salvage surgery was defined as salvage surgery performed within 9 months of the initial treatment.Results: Out of all the patients, 55 (36.4%) patients showed early tumor progression, 33 (34.4%) showed late tumor progression, and 63 (41.7%) showed non-progression. Patients who experienced early tumor progression had a median PPS of 5.2 months, while those with late tumor progression had a median PPS of 16.8 months (P < 0.001). Multivariable analysis revealed a robust independent correlation between early tumor progression and PPS (HR = 3.279, 95% CI: 1.591– 6.756; P = 0.001). Patients who received early salvage surgery showed a considerably lower early tumor progression rate when compared with patients who did not receive early surgery (12.5% vs 42.9%, P = 0.002). The multivariable analysis revealed that early salvage surgery was an independent factor influencing early tumor progression (OR = 0.246; 95% CI: 0.078– 0.773; P = 0.016).Conclusion: Early tumor progression is associated with worse PPS in patients with iuHCC receiving TTP therapy. Early salvage surgery can further improve patient outcomes by lowering the incidence of early progression.Keywords: Hepatocellular carcinoma, salvage surgery, early tumor progression, post-progression survival, real-world

Keywords

• hepatocellular carcinoma
• salvage surgery
• early tumor progression
• post-progression survival
• real-world