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

Background: 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 ( 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.