Plasma tumour DNA as an early indicator of treatment response in metastatic castration-resistant prostate cancer.

British Journal of Cancer
Vincenza ConteducaGerhardt Attard

Abstract

Plasma tumour DNA (ptDNA) levels on treatment are associated with response in a variety of cancers. However, the role of ptDNA in prostate cancer monitoring remains largely unexplored. Here we characterised on-treatment ptDNA dynamics and evaluated its potential for early assessment of therapy efficacy for metastatic castration-resistant prostate cancer (mCRPC). Between 2011 and 2016, 114 sequential plasma samples from 43 mCRPC abiraterone-treated patients were collected. Targeted next-generation sequencing was performed to determine ptDNA fraction. ptDNA progressive disease was defined as a rise in the fraction compared to the pre-treatment. A ptDNA rise in the first on-treatment sample (interquartile range (IQR) 2.6-3.7 months) was significantly associated with increased risk of early radiographic or any prostate-specific antigen (PSA) rise (odds ratio (OR) = 15.8, 95% confidence interval (CI) 3.5-60.2, p = 0.0002 and OR = 6.0, 95% CI 1.6-20.0, p = 0.01, respectively). We also identified exemplar cases that had a rise in PSA or pseudoprogression secondary to bone flare but no rise in ptDNA. In an exploratory analysis, initial ptDNA change was found to associate with the duration of response to prior androgen deprivation thera...Continue Reading

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Citations

Jan 17, 2021·Prostate Cancer and Prostatic Diseases·Takayuki SumiyoshiAlexander W Wyatt
Mar 13, 2021·Therapeutic Advances in Medical Oncology·Vincenza ConteducaUgo De Giorgi
Apr 10, 2021·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M AnnalaK N Chi
May 28, 2021·Expert Review of Molecular Diagnostics·Vincenza ConteducaUgo De Giorgi
Jul 15, 2021·Nature Cancer·Joaquin MateoHimisha Beltran
Oct 5, 2021·International Journal of Cancer. Journal International Du Cancer·Vincenza ConteducaUgo De Giorgi

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Methods Mentioned

BETA
biopsies
DNA Assay

Clinical Trials Mentioned

NCT02125357

Software Mentioned

CLONET
SAS

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