Comparison of Intraductal RFA Plus Stent versus Stent-Only Treatment for Unresectable Perihilar Cholangiocarcinoma—A Systematic Review and Meta-Analysis

Abstract

Background: One of the cornerstones of palliative treatment for unresectable perihilar cholangiocarcinoma is biliary stent placement in order to restore biliary drainage. In this review, the potential added value of RFA with stent placement in comparison to stent placement alone in patients with unresectable perihilar cholangiocarcinoma is analyzed. Methods: We performed a comprehensive online search for relevant articles in November 2021 (PROSPERO ID: CRD42021288180). The primary endpoint was difference in overall survival. Secondary endpoints included overall survival, stent patency and complications. Only studies comparing survival after RFA + stent placement with stent placement alone were included in the meta-analysis. Non-comparative studies or comparative studies describing stent patency only were included in the systematic review. Results: A total of nine studies, including 217 patients with pCCA who underwent RFA + stent placement and 294 patients who underwent stent-only treatment, met the inclusion criteria for the primary endpoint analysis. Direct comparison between the two treatment groups showed a significantly longer overall survival for RFA + stent treatment, with a pooled HR of 0.65 [95% CI, 0.50–0.84, I2 = 38%]. When all eligible studies were included, RFA + stent treatment revealed an overall survival of 9.5 months [95% CI, 6.3–12.6], whereas survival for stent-only treatment was 7.0 months [95% CI, 5.7–8.2]. Due to the heterogeneity of the data, no pooled data analysis could be performed on stent patency or complications. Conclusions: RFA + stent placement displays promising potential to prolong survival. However, further research incorporating confounding factors like use of palliative chemotherapy is necessary in order to validate these findings.

Efficacy and Safety of Radiofrequency Ablation Plus Stent Versus Stent-alone Treatments for Malignant Biliary Strictures

“…A recent meta-analysis that included 19 studies (3 RCT and 16 OS) suggests that RFA is associated with the improved survival and stent patency time of patients with MBO. 36 Another meta-analysis conducted by de Jong et al, 37 which included 9 articles and included a total of 511 patients with unresectable perihilar CCA, found that RFA treatment showed promising outcomes to improve patients' survival times. In their study, Song et al 38 showed the results of a Bayesian network meta-analysis of 33 trials with a total of 2974 patients.…”

Consensus statements on endoscopic radiofrequency ablation for malignant biliary strictures

“…The results showed that patients who received intraductal RFA had prolonged average OS (19 months vs 16 months, P = 0.04), improved quality of life, and more significantly improved liver and kidney functions 31 . Recent meta‐analyses have also suggested that compared to stenting alone, endobiliary RFA combined with stent implantation can prolong patient survival and stent patency in MBS without increasing the incidence of adverse events 32–35 . These studies include MBS of various etiologies, most of which are inoperable extrahepatic cholangiocarcinoma, including hilar and distal cholangiocarcinoma.

Recommendation 1: Endoscopic RFA is recommended for palliative treatment of inoperable extrahepatic cholangiocarcinoma.

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“…The incidences of complications in endobiliary RFA have been reported to range from 4.2% to 35%, including pancreatitis, cholangitis, cholecystitis, ampullary stenosis, and bleeding, 34,61 which are closely associated with the ERCP procedure, biliary drainage, tumor location, and the anatomical relationship with the adjacent organs. Several meta‐analyses have confirmed that RFA does not increase the additional risk of adverse events compared to conventional ERCP 32–35,61 . However, it may still lead to certain complications; therefore, sufficient attention should be paid to and active prevention and treatment should be taken for high‐risk patients.…”

Reply to Chandrasekhara and Aggarwal

“…In addition, there is a lack of information regarding the length and etiology of MBO. In an attempt to reduce the heterogeneity of the results, previous meta-analyses [2,3,4,5,6] included non-RCTs to increase the sample size. However, that measure does not increase the quality of evidence and should be evaluated with caution.…”