Authors' objectives: Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve outcomes in patients with malignant biliary obstruction. To assess the clinical effectiveness, cost-effectiveness and potential risks of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction, and the value of future research. The aim of this research was to establish the expected value of undertaking additional research to determine the clinical effectiveness, cost-effectiveness and safety of endoscopic bipolar radiofrequency ablation (RFA) for the treatment of malignant biliary obstruction. To carry out a systematic review to assess the clinical effectiveness and potential risks of endoscopic bipolar RFA for malignant biliary obstruction. To undertake a systematic review to assess the cost-effectiveness of endoscopic bipolar RFA for malignant biliary obstruction. To develop a decision model to estimate cost-effectiveness based on the data derived from the systematic reviews. To assess the value of further research by undertaking a value of information analysis from the data and results generated by the decision model.

Authors' results and conclusions: Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency. Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication. Clinical effectiveness review The search retrieved 4131 results after de-duplication, and update searches retrieved a further 287 de-duplicated results, giving a total of 4418 results. A total of 697 full-text results were screened in EndNote, and a total of 68 studies were included in the review. Eighteen studies were comparative studies and 50 were non-comparative studies, including a total of 1742 patients (plus one study that did not report participant numbers). A majority (53%) of results were conference abstracts with no peer-reviewed published report. Twenty-four studies were conducted in Asia, 20 in European countries, 20 in the USA, two in South American countries and two in Australia. Most patients had biliary obstruction arising from cholangiocarcinoma (where reported). The most commonly reported probe used for the ablation procedure was the Habib™ EndoHPB catheter (Boston Scientific Corporation, Marlborough, MA, USA) (n = 35), although many studies did not report the detail of the equipment used. Studies reported the insertion of a first stent (primary RFA; n = 40), the unblocking of an existing stent (secondary RFA; n = 15) or both (n = 11), but this was unclear in two studies. Risk-of-bias assessment One of the two published RCTs was judged to be at high risk of bias overall and one gave rise to ‘some concerns’. Four of the five published non-RCTs were judged to be at moderate risk of bias and one was judged to be at low risk of bias. Primary RFA appears to improve survival and is likely to be cost-effective; however, the evidence for this is mainly in patients with bile duct cancers rather than in patients with pancreatic cancers. Only 6 of 18 comparative studies could be included in the meta-analysis looking at survival because of the differences in outcome measures, but none reported a decrease in survival in the RFA group. There was no increased risk of cholangitis or pancreatitis following RFA, but possibly an increased risk of cholecystitis. There was a lack of high-quality data examining similar outcomes in patients undergoing secondary RFA. For both primary and secondary RFA, there were insufficient data to determine the effect of RFA on quality of life. Recommendations for further research include the following: Prospective RCTs of primary RFA should be conducted, with a specific focus on quality of life and accurate reporting of AEs in each group. Patients with pancreatic cancers should be classified separately from patients with bile duct cancers, to determine the effects of RFA in each group. The mechanism by which primary RFA has a beneficial effect on survival should be explored. Consideration should be given to whether or not a repeat application of RFA at a specified interval may further improve outcomes in patients with both pancreatic and bile duct cancers. High-quality prospective RCTs of secondary RFA should be carried out to determine whether or not there is benefit to survival and quality of life, including accurate reporting of AEs. These RCTs should also incorporate an assessment of cost-effectiveness. If benefit is shown in secondary RFA, an exploration of the mechanism should be carried out.

Authors' recommendations: Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency. Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication. Clinical effectiveness review The search retrieved 4131 results after de-duplication, and update searches retrieved a further 287 de-duplicated results, giving a total of 4418 results. A total of 697 full-text results were screened in EndNote, and a total of 68 studies were included in the review. Eighteen studies were comparative studies and 50 were non-comparative studies, including a total of 1742 patients (plus one study that did not report participant numbers). A majority (53%) of results were conference abstracts with no peer-reviewed published report. Twenty-four studies were conducted in Asia, 20 in European countries, 20 in the USA, two in South American countries and two in Australia. Most patients had biliary obstruction arising from cholangiocarcinoma (where reported). The most commonly reported probe used for the ablation procedure was the Habib™ EndoHPB catheter (Boston Scientific Corporation, Marlborough, MA, USA) (n = 35), although many studies did not report the detail of the equipment used. Studies reported the insertion of a first stent (primary RFA; n = 40), the unblocking of an existing stent (secondary RFA; n = 15) or both (n = 11), but this was unclear in two studies. Risk-of-bias assessment One of the two published RCTs was judged to be at high risk of bias overall and one gave rise to ‘some concerns’. Four of the five published non-RCTs were judged to be at moderate risk of bias and one was judged to be at low risk of bias. Primary RFA appears to improve survival and is likely to be cost-effective; however, the evidence for this is mainly in patients with bile duct cancers rather than in patients with pancreatic cancers. Only 6 of 18 comparative studies could be included in the meta-analysis looking at survival because of the differences in outcome measures, but none reported a decrease in survival in the RFA group. There was no increased risk of cholangitis or pancreatitis following RFA, but possibly an increased risk of cholecystitis. There was a lack of high-quality data examining similar outcomes in patients undergoing secondary RFA. For both primary and secondary RFA, there were insufficient data to determine the effect of RFA on quality of life. Recommendations for further research include the following: Prospective RCTs of primary RFA should be conducted, with a specific focus on quality of life and accurate reporting of AEs in each group. Patients with pancreatic cancers should be classified separately from patients with bile duct cancers, to determine the effects of RFA in each group. The mechanism by which primary RFA has a beneficial effect on survival should be explored. Consideration should be given to whether or not a repeat application of RFA at a specified interval may further improve outcomes in patients with both pancreatic and bile duct cancers. High-quality prospective RCTs of secondary RFA should be carried out to determine whether or not there is benefit to survival and quality of life, including accurate reporting of AEs. These RCTs should also incorporate an assessment of cost-effectiveness. If benefit is shown in secondary RFA, an exploration of the mechanism should be carried out.

Authors' methods: Seven bibliographic databases, three websites and seven trials registers were searched from 2008 until 21 January 2021. The study inclusion criteria were as follows: patients with biliary obstruction caused by any form of unresectable malignancy; the intervention was reported as an endoscopic biliary radiofrequency ablation to ablate malignant tissue that obstructs the bile or pancreatic ducts, either to fit a stent (primary radiofrequency ablation) or to clear an obstructed stent (secondary radiofrequency ablation); the primary outcomes were survival, quality of life or procedure-related adverse events; and the study design was a controlled study, an observational study or a case report. Risk of bias was assessed using Cochrane tools. The primary analysis was meta-analysis of the hazard ratio of mortality. Subgroup analyses were planned according to the type of probe, the type of stent (i.e. metal or plastic) and cancer type. A de novo Markov model was developed to model cost and quality-of-life outcomes associated with radiofrequency ablation in patients with primary advanced bile duct cancer. Insufficient data were available for pancreatic cancer and secondary bile duct cancer. An NHS and Personal Social Services perspective was adopted for the analysis. A probabilistic analysis was conducted to estimate the incremental cost-effectiveness ratio for radiofrequency ablation and the probability that radiofrequency ablation was cost-effective at different thresholds. The population expected value of perfect information was estimated in total and for the effectiveness parameters. Only 6 of 18 comparative studies contributed to the survival meta-analysis, and few data were found concerning secondary radiofrequency ablation. The economic model and cost-effectiveness meta-analysis required simplification because of data limitations. Inconsistencies in standard reporting and study design were noted. Clinical effectiveness review The systematic review followed robust published methods, was registered on PROSPERO (reference CRD42020170233) and is reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance. Eligibility criteria Population Patients with biliary obstruction caused by any form of unresectable malignancy.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR129784

Year Published: 2023

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/YYMN9802

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/YYMN9802

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk