Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

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.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000000303	Targeted cfDNA and WBC sequencing data from patients profiled in the study "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer". Note that 'Exome sequencing' is listed under Dataset Type since there is no option for targeted panel sequencing.	Illumina HiSeq 2500	1228

Publications	Citations
Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer. Fonseca NM, Maurice-Dror C, Herberts C, Tu W, Fan W, Murtha AJ, Kollmannsberger C, Kwan EM, Parekh K, Schönlau E, Bernales CQ, Donnellan G, Ng SWS, Sumiyoshi T, Vergidis J, Noonan K, Finch DL, Zulfiqar M, Miller S, Parimi S, Lavoie JM, Hardy E, Soleimani M, Nappi L, Eigl BJ, Kollmannsberger C, Taavitsainen S, Nykter M, Tolmeijer SH, Boerrigter E, Mehra N, van Erp NP, De Laere B, Lindberg J, Grönberg H, Khalaf DJ, Annala M, Chi KN, Wyatt AW. Nat Commun 15: 2024 1828	9

Publications

Citations

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer.
Fonseca NM, Maurice-Dror C, Herberts C, Tu W, Fan W, Murtha AJ, Kollmannsberger C, Kwan EM, Parekh K, Schönlau E, Bernales CQ, Donnellan G, Ng SWS, Sumiyoshi T, Vergidis J, Noonan K, Finch DL, Zulfiqar M, Miller S, Parimi S, Lavoie JM, Hardy E, Soleimani M, Nappi L, Eigl BJ, Kollmannsberger C, Taavitsainen S, Nykter M, Tolmeijer SH, Boerrigter E, Mehra N, van Erp NP, De Laere B, Lindberg J, Grönberg H, Khalaf DJ, Annala M, Chi KN, Wyatt AW. Nat Commun 15: 2024 1828