Repeat hepatectomy justified in patients with early recurrence of colorectal cancer liver metastases: A systematic review and meta-analysis

Highlights

• • High overall survival rates after repeat hepatectomy, even in patients suffering from very early recurrence of CRLM.
• • No consensus on the definition of early recurrence exists.
• • Disease-free interval should not be used as selection criterion per se for repeat hepatectomy.
• • A disease-free interval of more than twelve months is a favorable prognostic factor for overall survival after repeat hepatectomy.

Abstract

Background

The benefit of repeat hepatectomy in patients with early recurrence of colorectal cancer liver metastases (CRLM) is questioned, in particular in those suffering from recurrence within three to six months following initial hepatectomy. The aim of this review was therefore to assess whether disease-free interval was associated with overall survival in patients undergoing repeat hepatectomy for recurrent CRLM.

Methods

A systematic review and meta-analysis was conducted, according to PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched from database inception to 6th June 2020. Observational studies describing results of repeat hepatectomy for recurrent CRLM, including (disease-free) interval between hepatic resections and overall survival were included. Patients undergoing repeat hepatectomy within three months or additional resection of extrahepatic disease were excluded from meta-analysis.

Results

The initial search identified 2159 records, of which 28 were included for qualitative synthesis. A meta-analysis of 15 cohort studies was performed, comprising 1039 eligible patients. Median overall survival of 54.0 months [95 %-CI: 38.6–69.4] was observed after repeat hepatectomy in patients suffering from recurrent CRLM between three to six months compared to 53.0 months [95 %-CI: 44.3–61.6] for patients with recurrent CRLM between seven to twelve months (adjusted HR = 0.89, 95 %-CI: 0.66–1.18; p = 0.410), and 60.0 months [95 %-CI: 52.7–67.3] for patients with recurrent CRLM after twelve months (adjusted HR = 0.70, 95 %-CI: 0.53−0.92; p = 0.012).

Conclusions

Disease-free interval is considered a prognostic factor for overall survival, but should not be used as selection criterion per se for repeat hepatectomy in patients suffering from recurrent CRLM.

1

Introduction

Patients suffering from colorectal cancer liver metastases (CRLM) develop recurrent metastases in the liver remnant after initial treatment with curative intent in over 50 % of patients [ 1 , 2 ]. The majority of patients develop these recurrences within two years after initial hepatectomy [ 345 ]. Since 1980 repeat hepatic resections have been performed in highly selected patients. Ever since, low mortality and morbidity rates after these procedures were described [ 2 , 6 ]. Repeat hepatic resection is therefore considered a safe and effective treatment for patients with recurrence of CRLM [ 678 ].

Repeat hepatic resections were increasingly performed in the last decades, as developments in surgical techniques and minimally invasive local treatment strategies (i.e. thermal and microwave ablative techniques) resulted in a more aggressive approach towards treatment of recurrent CRLM [ 91011 ]. As result of this approach, and with the introduction of new systemic therapy regimens, improved overall survival rates have been reported for patient suffering from recurrent CRLM [ 12 ].

Selection of patients for repeat hepatectomy is based on technical and oncological aspects [ 13 ]. Multiple prognostic factors for overall survival after repeat hepatectomy have been identified to tailor selection of patients eligible for repeat hepatic resection. A disease-free interval (DFI) of less than twelve months between hepatic resections has been established as poor prognostic factor for overall survival [ 141516 ]. Although local treatment of metastases is the only treatment with curative intent, the potential benefit of repeat hepatectomy may be questioned in patients with short tumor doubling time, as these patients are believed to have an aggressive tumor biology [ 15 , 17 ]. Poor survival rates for patients with short DFI have been reported, particularly in patients suffering from new recurrences within three to six months [ 18192021 ]. However, no consensus on the definition of early recurrence exists [ 22232425 ]. As the potential benefit of repeat hepatectomy, in particular in patients with recurrence within six months following initial hepatectomy, is frequently debated in multidisciplinary team meetings, knowledge on the anticipated survival of patients undergoing repeat hepatectomy for early recurrence of CRLM could provide guidance. The aim of this review was therefore to assess whether a DFI of six months or less was associated with overall survival after repeat hepatectomy in patients suffering from recurrent CRLM.