Circulating tumor DNA and tissue complementarily detect genomic alterations in metastatic hormone-sensitive prostate...

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• The clinical utility of circulating tumor DNA (ctDNA) in hormone-sensitive prostate cancer (HSPC) is not fully understood.
• Tissue-based genomic profiling is standard, but liquid biopsies offer a less invasive alternative.
• Understanding ctDNA concordance with tissue is crucial for its integration into clinical practice.

Purpose of the Study:

• To evaluate the concordance between ctDNA and tissue genomic profiling in a large real-world cohort of HSPC patients.
• To assess the impact of disease burden on ctDNA abundance and detection rates.
• To identify genomic alterations associated with progression to castration-resistant prostate cancer (CRPC).

Main Methods:

• Retrospective analysis of a large, multicenter, real-world cohort of HSPC patients.
• Concordance analysis between ctDNA and tissue-based genomic profiling.
• Correlation of genomic alterations with disease progression and risk of CRPC.

Main Results:

• Diminished ctDNA abundance was observed in patients with low tumor burden.
• Concordance between ctDNA and tissue increased with disease burden.
• Exclusive genomic alterations were found in both ctDNA and tissue, particularly in high-volume metastatic disease.
• Specific gene alterations (BRCA1, BRCA2, CDK12, TP53, PTEN, RB1) and cumulative alterations were linked to shorter time to CRPC and escalated CRPC risk.

Conclusions:

• ctDNA analysis is a valuable tool in HSPC, complementing tissue profiling for detecting clinically relevant genomic alterations.
• The integration of both ctDNA and tissue analysis can improve the detection of actionable mutations.
• This approach holds potential for enhanced management strategies in advanced prostate cancer.