Current patterns of next-generation sequencing implementation in hepatocellular carcinoma in Spain

Hepatocellular carcinoma (HCC) is a major global health challenge with limited actionable genomic targets compared to other gastrointestinal malignancies. Despite this, next-generation sequencing (NGS) is gaining traction for research and precision oncology applications. This study evaluates the current landscape of NGS implementation for HCC in clinical practice across Spain.

A national cross-sectional survey was conducted in 2025 among experts from Spanish oncology centers. The survey assessed the availability of NGS, the timing of testing, common genomic alterations sought, and the clinical impact of molecular profiling in HCC management.

Of the 54 responding centers, only 15% (8/54) currently perform NGS specifically for HCC; all subsequent analyses of testing patterns, biomarkers, and clinical impact are therefore based on this small subset of 8 centers and are reported here with absolute numbers alongside percentages. NGS-performing centers were most frequently located in Catalonia (3/54, 6%) and Madrid (3/54, 6%), although the denominator of responding centers per region was not available and regional comparisons should be interpreted cautiously. NGS was predominantly utilized in advanced disease stages (4/8, 50%) or refractory settings (2/8, 25%). The most frequently analyzed genomic alterations included MET (5/8, 62.5%), TP53, CTNNB1, and PTEN (4/8 each, 50%), and TERT (3/8, 37.5%); most of these alterations currently have limited or no validated therapeutic actionability in HCC and largely reflect standard broad-panel content rather than predictive testing. Notably, 75% (6/8) of centers performing NGS reported access to specialized genetic counseling or molecular tumor boards for interpreting complex NGS results.

In this survey, NGS was infrequently used for HCC among participating Spanish centers, mainly in the advanced or refractory setting and predominantly within institutions with established precision-oncology infrastructure. Given the small number of NGS-performing centers and the current lack of a validated predictive biomarker in HCC, these findings should be interpreted as descriptive of current practice, rather than as evidence of unmet need, and may serve as a baseline for future comparisons.