Related Experiment Video
Updated: Jan 12, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Baseline and Early On-treatment Circulating Tumour DNA Fraction Are a Key Prognostic Biomarker in Metastatic
Heidi Fettke1, Louise Kostos2, Maria Docanto3
1Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Clinical Genomics, School of Translational Medicine, Monash University, Melbourne, Australia.
Background And Objective:
The prostate-specific membrane antigen (PSMA)-targeted radioligand [177Lu]Lu-PSMA-617 is an approved treatment for metastatic castration-resistant prostate cancer (mCRPC). However, identification of genomic biomarkers associated with treatment efficacy remains a critical unmet need.
Methods:
We used a customized 78-gene panel to analyse circulating tumour DNA (ctDNA) from 150 patients with mCRPC included in a prospective [177Lu]Lu-PSMA-617 registry.
Key Findings And Limitations:
Undetectable ctDNA was a significant and positive prognostic biomarker at both baseline (before treatment) and at week 6 (before cycle 2 of [177Lu]Lu-PSMA-617). Quantification of the baseline ctDNA fraction enhanced prognostic stratification irrespective of high or low PSMA expression on position emission tomography imaging. Undetectable ctDNA at week 6 was linked to a superior treatment benefit independent of prostate-specific antigen response. FOLH1 alterations were identified as a potential novel therapeutic resistance mechanism.
Conclusions And Clinical Implications:
Our data highlight the potential utility of ctDNA in optimising patient selection, improving therapeutic monitoring, and dissecting genomic mechanisms of resistance to [177Lu]Lu-PSMA-617, and further prospective validation is warranted.
