How the map is built
The map follows a protocol registered in PROSPERO and is reported according to PRISMA 2020 and current guidance for evidence and gap maps. This page summarises the methods; full details are in the published article and its supplement.
Search and eligibility
Sources
Embase, MEDLINE and the Cochrane Database of Systematic Reviews, searched via Ovid from 1 January 2010 to 30 March 2026, with backward citation searching. The start date marks the contemporary therapeutic era opened by sorafenib and the PRISMA statement. English-language reports only.
Included reviews
Systematic reviews with meta-analysis of comparative studies in adults with HCC at any stage: randomised trials, prospective cohorts, or retrospective studies adjusted for confounding. Each review compares at least two options among the prespecified treatments.
Excluded: reviews without quantitative synthesis, single-arm meta-analyses, mixed liver cancers without HCC-specific data, paediatric populations, non-therapeutic comparators other than best supportive care, investigational treatments, conference abstracts and retracted publications.
Treatment taxonomy
Treatments are coded in nine extraction categories and grouped into the seven tiers of the multiparametric therapeutic hierarchy. Synonyms and specific labels are mapped to a controlled vocabulary.
| Tier | Treatment | Includes |
|---|---|---|
| LT | Liver transplantation | Living- or deceased-donor |
| LR | Liver resection | Open or minimally invasive |
| ABL | Ablation | Radiofrequency, microwave and other percutaneous ablation |
| EBRT | External-beam radiotherapy | Including stereotactic body radiotherapy |
| IAT | Intra-arterial therapies | Chemoembolization, bland embolization, radioembolization, hepatic arterial infusion chemotherapy |
| ST | Systemic therapies | Immunotherapy-based regimens, kinase inhibitors and anti-angiogenic agents |
| BSC | Best supportive care | Comparator only |
Four comparison classes
Inter-category treatment comparison
Arms from different extraction categories.
Resection vs ablation; immunotherapy- vs kinase-inhibitor-based regimens.
Combination strategy
Two or more categories used together, compared with a component or another strategy.
Chemoembolization plus systemic therapy vs chemoembolization alone.
Intra-category technical variant
Arms from the same category that differ in technique, device, agent or regimen.
Open vs minimally invasive resection; lenvatinib vs sorafenib.
Sequential strategy
A planned sequence around an anchor treatment, following the converse therapeutic hierarchy.
Neoadjuvant, adjuvant, bridging, downstaging/conversion or salvage intent.
Selection, extraction and quality control
Records are de-duplicated in Covidence and screened on title/abstract and full text by two reviewers independently, with disagreements resolved by consensus. Eleven trained extractors complete a piloted form covering search methods, primary-study designs, network meta-analysis, quality appraisal, GRADE, population and BCLC restrictions, sample size, outcomes and the treatment comparison.
The whole dataset is checked with scripted, rule-based procedures: controlled-vocabulary matching, format validation, comparator order, duplicates and cross-field consistency. Every automated change is logged with its value before and after. These checks verify internal consistency, not the accuracy of extracted values against the source reports. AMSTAR 2 appraisal is in progress.
Living updates and governance
| Search | Re-run with the same strategy once a year during the first phase, then every six months |
|---|---|
| Release | Numbered, dated version of the map and the dataset, with a change log of reviews added, removed and corrected |
| Retractions | Checked at each update; retracted reviews leave the active map and remain traceable in archived versions |
| Error reports | Users can report errors or missing reviews: alessandro.vitale@unipd.it |
| Data platform | From the umbrella-review phase, the dataset moves to a REDCap database with controlled fields and an audit trail |