Genomic profiles and clinical outcomes in primary versus secondary metastatic hormone-sensitive prostate cancer.
Prostate
; 81(9): 572-579, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33955569
ABSTRACT
BACKGROUND:
Clinical outcomes may differ among patients presenting with primary (de novo) metastatic hormone-sensitive prostate cancer (mHSPC) versus secondary (metachronous) mHSPC occurring after local therapy. It is unknown what molecular features distinguish these potentially distinct presentations.METHODS:
A single-center retrospective study of mHSPC patients classified as primary mHSPC (n = 121) or secondary mHSPC (n = 106). A targeted set of genes was analyzed BRCA2, PTEN, RB1, TP53, SPOP, CDK12, any two out of PTEN/RB1/TP53 alterations, and homologous recombination deficiency mutations. TP53 mutations were categorized as loss-of-function (LOF) versus dominant-negative (DN). The impacts of genetic features on progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards regression.RESULTS:
Median PFS was 15 and 30 months for men with primary and secondary mHSPC, respectively (hazard ratio 0.57, 95% confidence interval 0.41-0.78; p < .01). OS did not show a significant difference between groups. There were more men with Gleason 8-10 disease in the primary versus secondary mHSPC groups (83% vs. 68%; p < .01). In univariate and multivariate analyses, TP53 DN mutations showed a statistically significant association with OS for the entire mHSPC population. Conversely, SPOP mutations were associated with improved OS. Additionally, TP53 mutations (DN and LOF) were associated with worse OS for secondary mHSPC. A combination of PTEN/RB1/TP53 mutations was associated with worse OS and PFS for secondary mHSPC, while no genomic alteration affected outcomes for primary mHSPC.CONCLUSIONS:
TP53 DN mutations, but not all TP53 alterations, were the strongest predictor of negative outcomes in men with mHSPC, while SPOP mutations were associated with improved outcomes. In subgroup analyses, specific alterations were prognostic of outcomes in secondary, but not primary, mHSPC.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Proteínas Repressoras
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Proteínas Nucleares
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Genes p53
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Segunda Neoplasia Primária
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Neoplasias Hormônio-Dependentes
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Prostate
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos