No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear.
Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org ). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.
Nature communications. 2024 Feb 28*** epublish ***
Nicolette M Fonseca, Corinne Maurice-Dror, Cameron Herberts, Wilson Tu, William Fan, Andrew J Murtha, Catarina Kollmannsberger, Edmond M Kwan, Karan Parekh, Elena Schönlau, Cecily Q Bernales, Gráinne Donnellan, Sarah W S Ng, Takayuki Sumiyoshi, Joanna Vergidis, Krista Noonan, Daygen L Finch, Muhammad Zulfiqar, Stacy Miller, Sunil Parimi, Jean-Michel Lavoie, Edward Hardy, Maryam Soleimani, Lucia Nappi, Bernhard J Eigl, Christian Kollmannsberger, Sinja Taavitsainen, Matti Nykter, Sofie H Tolmeijer, Emmy Boerrigter, Niven Mehra, Nielka P van Erp, Bram De Laere, Johan Lindberg, Henrik Grönberg, Daniel J Khalaf, Matti Annala, Kim N Chi, Alexander W Wyatt
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada., Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada., Department of Medical Oncology, BC Cancer, Victoria, BC, Canada., Department of Medical Oncology, BC Cancer, Surrey, BC, Canada., Department of Medical Oncology, BC Cancer, Kelowna, BC, Canada., Department of Medical Oncology, BC Cancer, Abbotsford, BC, Canada., Department of Radiation Oncology, BC Cancer, Prince George, BC, Canada., Tom McMurtry & Peter Baerg Cancer Centre, Vernon Jubilee Hospital, Vernon, BC, Canada., Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland., Department of Pharmacy, Research Institute for Medical Innovation, Radboud University, Nijmegen, The Netherlands., Department of Medical Oncology, Research Institute for Medical Innovation, Radboud University, Nijmegen, The Netherlands., Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. ., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. ., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/38418825