Published online Jun 27, 2018. doi: 10.4254/wjh.v10.i6.433
Peer-review started: November 30, 2017
First decision: December 27, 2017
Revised: February 10, 2018
Accepted: March 3, 2018
Article in press: March 3, 2018
Published online: June 27, 2018
Hepatocellular carcinoma (HCC) remains a significant disease burden worldwide today. Appropriate treatment for HCC is complex because radical oncological clearance and preservation of adequate liver function need to be carefully balanced. Several staging systems have been developed to guide management of HCC.
Surgical resection for HCC within the “Milan Criteria” or Barcelona Clinic Liver Cancer (BCLC) stage A is the widely accepted standard of care. However, surgical treatment for BCLC stage B (intermediate) or C (advanced) lesions remains controversial. Presently, the European Association for the Study of Liver Disease (EASL) and the American Association for the Study of Liver Disease (AASLD) guidelines do not recommend surgical resection for these patients. However, despite the recommendations from these two large reputable organizations, many international high-volume tertiary centers, especially centers in Asia, still routinely perform surgical resection for large solitary lesions, multifocal lesions and lesions with macrovascular invasion. Critical appraisal of both Western and Asian literature is needed to resolve the controversies.
The aim of this study was to perform a systematic review and summarize the current literature to determine the long-term survival outcomes after curative resection of intermediate and advanced HCCs.
We conducted a systematic review of the published literature using the PubMed database from 1st January 1999 to 31st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for BCLC stage B or C HCC. The primary end point was to determine the overall survival (OS) and disease free survival (DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve (i.e., Child’s A or B status) and in good general status (PS 0-2). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC (defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC.
We included a total of 74 articles in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to: (1) BCLC stage B or C HCC; (2) Size of HCC; and (3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7% (range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0% (range 0.0-42.0). The collective median 5-year OS of both stages was 27.9% (0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR (95%CI): 1.00 (0.76-1.31)] and mortality [RR (95%CI): 1.15 (0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%.
In conclusion, the results of the current systematic review provides evidence that indications for surgical resection of HCC should be extended to include selected BCLC stage B lesions and further studies should seek to identify the optimal criteria for the consideration of the criteria for liver resection.
As evidenced by the results of this systematic review, long-term survival results after surgical resection are acceptable and represent the best possible therapeutic option for selected BCLC stage B HCC. This review showed that resection beyond criteria advised by the AASLD and EASL guidelines, has achieved survival exceeding that accorded by non-curative methods such as TACE and sorafenib which typically confers a median OS between 8-12 mo. Further studies should seek to identify the optimal criteria for the consideration of the criteria for liver resection.