Genomic instability is associated with response to [¹⁷⁷Lu]Lu-PSMA-I&T radioligand therapy: an exploratory, preliminary liquid biopsy analysis.
case_series · Level IV
Where this comes from
- Record sourced from PubMed, PMID 40261406.
- Also identified by DOI 10.1007/s00259-025-07280-5 and PMC identifier 12397107.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
PSMA-targeted radioligand therapies (PSMA RLT) are an effective and safe option for metastatic castration-resistant prostate cancer, but responsive subtypes and their biomarkers are not fully defined. Plasma samples for cell-free DNA (cfDNA) analysis were collected from 17 patients undergoing [¹⁷⁷Lu]Lu-PSMA-I&T. CfDNA underwent whole-genome sequencing to establish copy number variation (CNV) profiles and circulating-tumor DNA (ctDNA) levels and compared between prostate-specific antigen (PSA) response- and 1-year overall survival (1YOS) groups. Non-responders exhibited higher degrees of cfDNA CNV burden (P = 0.048) and higher ctDNA levels (P = 0.036) than responders. Both markers allowed for the differentiation of responses (AUC: 0.792, 0.806) and 1YOS (AUC: 0.778, 0.847). Unresponsive patients exhibited higher levels of cfDNA genomic instability and ctDNA levels, warranting genome-wide CNV profiling studies next to targeted approaches for mechanistic radiobiological insights and their value as response biomarkers for PSMA RLTs.
Medical subject headings
- Genomic Instability
- Prostatic Neoplasms, Castration-Resistant
- Circulating Tumor DNA
- Radiopharmaceuticals