Detection of ctDNA in plasma of patients with clinically localised prostate cancer is associated with rapid disease progression.
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BORIS DOI
Publisher DOI
PubMed ID
32807235
Description
BACKGROUND
DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown.
METHODS
We performed whole-genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 h and 6 weeks) surgery. In a separate cohort (n = 189), we identified the presence of ctDNA TP53 mutations in preoperative plasma in a retrospective cohort and determined its association with biochemical- and metastasis-free survival.
RESULTS
Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2-4.8, p = 0.014).
CONCLUSIONS
CtDNA is uncommonly detected in localised prostate cancer, but its presence portends more rapidly progressive disease.
DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown.
METHODS
We performed whole-genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 h and 6 weeks) surgery. In a separate cohort (n = 189), we identified the presence of ctDNA TP53 mutations in preoperative plasma in a retrospective cohort and determined its association with biochemical- and metastasis-free survival.
RESULTS
Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2-4.8, p = 0.014).
CONCLUSIONS
CtDNA is uncommonly detected in localised prostate cancer, but its presence portends more rapidly progressive disease.
Date of Publication
2020-08-17
Publication Type
Article
Subject(s)
Language(s)
en
Contributor(s)
Lau, Edmund | |
McCoy, Patrick | |
Reeves, Fairleigh | |
Chow, Ken | |
Clarkson, Michael | |
Kwan, Edmond M | |
Packwood, Kate | |
Northen, Helen | |
He, Miao | |
Kingsbury, Zoya | |
Mangiola, Stefano | |
Kerger, Michael | |
Crowe, Helen | |
Costello, Anthony J | |
McBride, David J | |
Ross, Mark T | |
Pope, Bernard | |
Hovens, Christopher M | |
Corcoran, Niall M |
Additional Credits
Series
Genome medicine
Publisher
BioMed Central
ISSN
1756-994X
Access(Rights)
open.access