Conversion therapy and suitable timing for subsequent salvage surgery for initially unresectable hepatocellular carcinoma: What is new?

ARTICLE HIGHLIGHTS

Research background

Hepatocellular carcinoma (HCC) is a primary cancer of the liver and is the fifth most prevalent cancer in men and the seventh in women worldwide. Hepatectomy is currently the first-line curative therapy, but about 30% of lesions are resectable at the time of diagnosis. Conversion therapy is used to increase the resectability of initially unresectable HCC by increasing the size of the future liver remnant (FLR) or downstaging the tumor, followed by salvage surgery. Although various preoperative therapies provide initially unresectable HCC patients with the chance to undergo curative resection, the suitable timing of the subsequent salvage surgery remains uncertain and controversial.

Research motivation

Only 10%-30% HCC patients can obtain the chance to undergo surgery at the time of diagnosis. Those who are not suitable for curative surgery may benefit from conversion therapy and seize the opportunity to undergo salvage surgery when they reach the “timing”. Therefore, we review the types of conversion therapy and the suitable timing for salvage surgery.

Research objectives

To review the conversion therapy for initially unresectable HCC patients and the suitable timing for subsequent salvage surgery, and we finally hope to increase the 5-year survival rate of HCC patients.

Research methods

A PubMed search was undertaken from 1987 to 2017 to identify articles using the key words including “unresectable” “hepatocellular carcinoma”, ”hepatectomy”, ”conversion therapy”, “resection”, “salvage surgery” and “downstaging”. Additional studies were investigated through a manual search of the references from the articles. The exclusion criteria were duplicates, case reports, case series, videos, contents unrelated to the topic, comments, and editorial essays. The main and widely used conversion therapies and the suitable timing for subsequent salvage surgery were discussed in detail. Two members of our group independently performed the literature search and data extraction.

Research results

Liver volume measurements (FLR/total liver volume or residual liver volume/bodyweight ratio) and function tests (scoring systems and liver stiffness) were often performed in order to justify whether patients were suitable candidates for surgery. Successful conversion therapy was usually defined as downstaging the tumor, increasing FLR and providing subsequent salvage surgery, without increasing complications, morbidity or mortality. The requirements for performing salvage surgery after transcatheter arterial chemoembolization (TACE) were the achievement of a partial remission in radiology, the disappearance of the portal vein thrombosis (PVT), and the lack of extrahepatic metastasis. Patients with a standardized FLR (sFLR) > 20% were good candidates for surgery after portal vein embolization (PVE), while other predictive parameters like growth rate (GR), kinetic growth rate (KGR) were treated as an effective supplementary. There was probably not enough evidence to provide a standard operation time after associating liver partition and portal vein ligation for staged hepatectomy (ALLPS) or yttrium-90 microsphere radioembolization (RE). The indications of any combinations of conversion therapies and the subsequent salvage surgery time still need to be carefully and comprehensively evaluated.

Research conclusion

Conversion therapy is recommended for the treatment of initially unresectable HCC, and the suitable subsequent salvage surgery time should be reappraised and is closely related to its previous therapeutic effect.

Research perspectives

For the initially unresectable HCC patients, conversion therapies such as TACE, PVE, ALPPS, yttrium-90 RE, and sequential TACE and PVE have been demonstrated to be effective and should be performed. Both morphological and functional examinations need to be undertaken to estimate the therapeutic effect before salvage surgery. Controlling a good operative time and selecting a reasonable procedure are important for improving the operative efficacy. The reasonable unified application of conversion therapy and salvage surgery can improve the curative effect and increase the survival rate of patients.