LIQUID BIOPSY-BASED genomic profiling could offer a reliable and less invasive alternative to tissue sampling in patients with high-risk localised prostate cancer, particularly where tumour tissue is limited or of poor quality, according to a new study.
Genomic profiling is increasingly used to guide treatment decisions by identifying tumour-specific mutations. While liquid biopsies, tests that analyse circulating tumour DNA (ctDNA) in blood, are already established in metastatic prostate cancer, their role in localised disease has remained uncertain due to typically low levels of ctDNA.
In this phase 2 neoadjuvant study, researchers evaluated both tissue- and plasma-based genomic profiling in patients with high-risk localised disease. The team analysed DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour samples alongside cell-free DNA from plasma, using the Illumina TruSight Oncology 500 platform and advanced bioinformatics pipelines.
Higher Success Rates with Liquid Biopsy
The findings revealed a marked difference in sequencing success rates between the two approaches. Of 22 tissue biopsy samples, only 54.5% yielded usable genomic data, with failures largely attributed to insufficient DNA quality or quantity. In contrast, all 27 plasma samples were successfully sequenced, despite the anticipated challenge of low ctDNA levels in localised disease.
Both tissue and liquid biopsy approaches identified a similar average of 3.5 genomic alterations per sample. Detected mutations included clinically relevant genes such as SPOP, ATRX, ATM, and ARID1B, which are known to play roles in prostate cancer biology. Notably, liquid-based profiling demonstrated superior sequencing depth and coverage, enabling the detection of low-frequency mutations that may be missed with tissue analysis.
Direct comparison between matched tissue and plasma samples was limited, as only four patients had paired data available for concordance analysis. As a result, the degree of agreement between the two methods could not be robustly established.
Need for Larger Studies to Confirm Clinical Utility
Despite this limitation, the study provides encouraging evidence that liquid biopsy is both feasible and technically robust in high-risk localised prostate cancer. The authors suggest that plasma-based genomic profiling could serve as a valuable complementary tool, particularly in cases where tissue biopsies are inadequate or impractical.
Further large-scale studies are needed to confirm concordance between methods and to determine how liquid biopsy findings can be integrated into clinical decision-making for patients with localised disease.
Reference
Bettoni F et al. Liquid-based genomic profiling in high-risk localized prostate cancer. Front Urol. 2026; 6:1789586.
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