Transplant Library

Abstract

OBJECTIVE:

To systematically review studies reporting survival data following neoadjuvant chemoradiation and orthotopic liver transplantation (NCR-OLT) for unresectable perihilar cholangiocarcinoma (pCC).

BACKGROUND:

Despite survival improvements for other cancers, the prognosis of pCC remains dismal. Since publication of the Mayo protocol in 2000, increasing numbers of series globally are reporting outcomes after NCR-OLT.

METHODS:

MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from January 2000 to February 2019. A meta-analysis of proportions was conducted, pooling 1, 3-, and 5-year overall survival and recurrence rates following NCR-OLT across centers. Per protocol and intention to treat data were interrogated. Meta-regression was used to evaluate PSC as a confounder affecting survival.

RESULTS:

Twenty studies comprising 428 patients were eligible for analysis. No RCTs were retrieved; the majority of studies were noncomparative cohort studies. The pooled 1, 3-, and 5-year overall survival rates following OLT without neoadjuvant therapy were 71.2% (95% CI 62.2%-79.4%), 48.0% (95% CI 35.0%-60.9%), and 31.6% (95% CI 23.1%-40.7%). These improved to 82.8% (95% CI 73.0%-90.8%), 65.5% (95% CI 48.7%-80.5%), and 65.1% (95% CI 55.1%-74.5%) if neoadjuvant chemoradiation was completed. Pooled recurrence after 3 years was 24.1% (95% CI 17.9%-30.9%) with neoadjuvant chemoradiation, 51.7% (95% CI 33.8%-69.4%) without.

CONCLUSIONS:

In unresectable pCC, NCR-OLT confers long-term survival in highly selected patients able to complete neoadjuvant chemoradiation followed by transplantation. PSC patients appear to have the most favorable outcomes. A high recurrence rate is of concern when considering extending national graft selection policy to pCC.

CET Conclusion

Reviewer:	Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:	The systematic review evaluated survival after liver transplantation for unresectable perihilar cholangiocarcinoma (pCC). A senior information specialist assisted to develop a comprehensive literature search from 2000-2019. Study selection was done by two independent reviewers, quality assessment using the Newcastle-Ottawa scale was conducted by three independent reviewers and data extraction was done by a single reviewer. The study included 20 observational studies of which 16 were assessed as being of poor methodological quality. The authors provided a detailed description of surgical techniques and adjunctive procedures that varied between studies. Survival for all patients after liver transplantation for pCC was 76.9% at 1 year (18 studies), 55.3% at 3 years (13 studies) and 44.9% at 5 years (10 studies). However, survival increased after undergoing a neoadjuvant protocol to 82.8%, 65.5% and 65.1 at 1, 3 and 5 year, respectively. To explore potential sources of heterogeneity meta-regression analysis investigated whether there was a correlation between the proportion of patients with PSC and survival. There was no significant correlation for the 3-year survival data but there was a positive, significant correlation for 5-year survival data. Disease recurrence was analysed for studies that followed patients for at least 3 years. The analysis showed an overall recurrence rate of 29.4% (8 studies), with a recurrence rate of 24.1% for patients who had neoadjuvant therapy (6 studies) and 51.7% for patients who did not have neoadjuvant therapy (2 studies).

Reviewer:

Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford

Conclusion:

The systematic review evaluated survival after liver transplantation for unresectable perihilar cholangiocarcinoma (pCC). A senior information specialist assisted to develop a comprehensive literature search from 2000-2019. Study selection was done by two independent reviewers, quality assessment using the Newcastle-Ottawa scale was conducted by three independent reviewers and data extraction was done by a single reviewer. The study included 20 observational studies of which 16 were assessed as being of poor methodological quality. The authors provided a detailed description of surgical techniques and adjunctive procedures that varied between studies. Survival for all patients after liver transplantation for pCC was 76.9% at 1 year (18 studies), 55.3% at 3 years (13 studies) and 44.9% at 5 years (10 studies). However, survival increased after undergoing a neoadjuvant protocol to 82.8%, 65.5% and 65.1 at 1, 3 and 5 year, respectively. To explore potential sources of heterogeneity meta-regression analysis investigated whether there was a correlation between the proportion of patients with PSC and survival. There was no significant correlation for the 3-year survival data but there was a positive, significant correlation for 5-year survival data. Disease recurrence was analysed for studies that followed patients for at least 3 years. The analysis showed an overall recurrence rate of 29.4% (8 studies), with a recurrence rate of 24.1% for patients who had neoadjuvant therapy (6 studies) and 51.7% for patients who did not have neoadjuvant therapy (2 studies).

Study Details

Aims:	The systematic review aimed to summarise the reported survival and recurrence rate after neoadjuvant chemoradiation and orthotopic liver transplantation (NCR-OLT) for unresectable perihilar cholangiocarcinoma (pCC).
Interventions:	Neoadjuvant chemoradiation and orthotopic liver transplantation
Participants:	Patients with unresectable pCC undergoing NCR-OLT
Outcomes:	The primary outcome was overall survival at 1, 3 and 5 years and the secondary outcome was the recurrence rate at 3 years.
Follow Up:	5 year

Metadata

Publication type:	Meta-Analysis, Systematic Review
Review registration:	CRD42019127662
Organ:	Liver
Language:	English
Author email:	rachel.guest@ed.ac.uk
MeSH terms:	Bile Duct Neoplasms; Humans; Klatskin Tumor; Liver Transplantation; Regression Analysis; Survival Rate; Funding - None

Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma