DNA-repair status should be assessed in treatment-emergent neuroendocrine prostate cancer before platinum-based therapy.
Prostate
; 82(4): 464-474, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35037281
ABSTRACT
OBJECTIVES:
This study sought to provide contemporary data from a multi-institution with respect to DNA-repair genes (DRGs) status and its impact on effects of platinum-based chemotherapy in treatment-emergent neuroendocrine prostate cancer (t-NEPC), for which little data exist. PATIENTS ANDMETHODS:
All patients were retrospectively collected with eligible biopsied tissues for targeted next generation sequencing (NGS). The main outcomes were radiologic progression-free survival and overall survival according to Response Evaluation Criteria in Solid Tumors, version 1.1.RESULTS:
Among the 43 NEPC patients, 13/43 (30%) harbored homozygous deletions, deleterious mutations, or both in DRGs. Eleven patients (11/13, 85%) with DRGs aberrations had effective response, including 7 patients with BRCA1/2 defects and 2 with mismatch repair-deficient caused by MSH2 alterations. While significantly fewer responders (30%) were detected in patients without DRGs aberrations (odds ratio = 12.83, p = 0.003). Compared with patients without genomic DRGs aberrations, the hazard ratio (HR) for radiologic progression in those with DRGs defects was 0.42 (95% confidence interval [CI] 0.19-0.93), and the HR for death was 0.65 (95% CI 0.24-1.72). The most common adverse event of Grade 3 or 4 was anemia, as noted in 7 patients (16%).CONCLUSION:
The DRGs status is therapeutically meaningful in t-NEPC. Given the potential responses to platinum-based chemotherapy, our findings support the clinical use of NGS in t-NEPC patients to identify DRGs aberrations.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Compostos de Platina
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Carcinoma Neuroendócrino
/
Reparo do DNA
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article