Analysis of the Prognostic Significance of Circulating Tumor DNA in Metastatic Castrate Resistant Prostate Cancer.
Clin Genitourin Cancer
; 19(6): 564.e1-564.e10, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34452870
ABSTRACT
BACKGROUND:
There has been considerable interest in ctDNA next generation sequencing platforms to assess genomic alterations in mCRPC given its accessibility and identification of temporal genomic data. PATIENTSANDMETHODS:
In this retrospective analysis, we analyzed 63 patients who underwent ctDNA genomic profiling during their mCRPC disease course using a CLIA-certified commercial assay. The primary objective was to assess the feasibility of commercial ctDNA analysis in a real world mCRPC cohort. Key secondary objectives included assessment of the landscape of pathogenic ctDNA alterations and the prognostic significance of ctDNA detection on overall survival (OS).RESULTS:
Among the cohort, at the time of ctDNA collection, median age was 70 years, and 47.6% (N = 30/63) had bone-only metastases. ctDNA was detected in the majority of patients with at least 1 pathogenic alteration detected in 90.5% (N = 57/63) of individuals. The most common alterations detected were in AR, TP53, and PIK3CA. Actionable alterations with FDA-approved therapies were found in 15.8% (N = 10) of the cohort. The presence of ≤ 1 versus > 1 alteration on ctDNA analysis was strongly associated with inferior OS with a median OS of 26.1 versus 8.8 months, respectively (HR = 7.0, 95% CI, 2.2-23.1, P < .001). In multivariate analysis, the number of detected alterations remained a significant predictor for OS. Lastly, there was weak correlation between Prostate-Specific Antigen (PSA), and ctDNA characteristics.CONCLUSION:
ctDNA is a viable next generation sequencing (NGS) platform in mCRPC and can be utilized to identify actionable alterations. The presence and extent of ctDNA alterations appear to be prognostic of OS in mCRPC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Próstata Resistentes à Castração
/
DNA Tumoral Circulante
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Humans
/
Male
Idioma:
En
Revista:
Clin Genitourin Cancer
Assunto da revista:
NEOPLASIAS
/
UROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá