Ablative and non-invasive therapies for early and very early hepatocellular carcinoma: a systematic review and network meta-analysis

Design: Systematic review and network meta-analysis

Aim: The aim of this project is to review and compare the effectiveness of all current ablative and non-invasive therapies for patients with hepatocellular carcinoma (HCC) where tumours are small (up to 3cm). The focus will be on outcomes of most relevance to patients, including improvement in survival and quality of life.

Background: Over the last decade, the UK incidence of liver cancer has increased by 60% and is projected to rise further. This increase is largely driven by an increase in the prevalence of cirrhosis. HCC is often asymptomatic until late in its disease course and the prognosis of HCC patients presenting with symptoms is poor.

It is therefore important to diagnose HCC early, when treatment may improve outcomes. A wide range of ablative and non-invasive therapies is available for treating small HCC tumours in patients with very early or early stage disease and preserved liver function.

Rising HCC incidence, coupled with uncertainty about the effectiveness of the available therapies, necessitates a thorough systematic evaluation of the existing relevant research evidence. Assessment of the quality and applicability of this evidence will be important in judging suitability for inclusion in evidence syntheses designed to inform both UK clinical practice and the design of future effectiveness and cost-effectiveness studies of emerging treatments.

Methods: A systematic review of all published and unpublished randomised controlled trials (RCTs) of ablative and non-invasive therapies for HCC will be undertaken, following CRD’s guidance on conducting systematic reviews. The resulting RCT evidence base will be quality assessed and mapped. The comparative effectiveness of therapies will then be determined using network meta-analysis.

A threshold analysis will be used to identify which comparisons are sensitive to changes due to insufficient RCT evidence. Where the RCT evidence is insufficient, targeted systematic reviews of high quality, non-randomised, prospective comparative studies of specific therapies will provide additional data for repeat network meta-analysis and threshold analysis.

The feasibility of undertaking economic modelling of relevance and interest to the NHS will be explored. A workshop with patients and clinicians will be organised to discuss our findings and identify key priorities for future research.

Dissemination: Choice of dissemination activities will be informed by the key messages generated and will take account of the needs and preferences of the target audiences. A final report for the NIHR HTA Programme will be produced, along with the submission of manuscripts for peer-reviewed publication and a conference abstract. The CRD website and social media will also be used to disseminate findings, and brief evidence summaries will be produced.