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Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report.

ABSTRACT: BACKGROUND:Precision medicine based on genomic analysis of germline or tumor tissue is attracting attention. However, there is no consensus on how to apply the results of genomic analysis to treatment. CASE PRESENTATION:A 59-year-old man diagnosed with metastatic prostate cancer was diagnosed with castration-resistant prostate cancer. Although he was sequentially treated with enzalutamide and abiraterone, bone metastasis progression was identified by skeletal scintigraphy. Therefore, we sequentially performed docetaxel therapy followed by cabazitaxel. After the third cycle of cabazitaxel, his prostate-specific antigen level was stable at

SUBMITTER: Hongo H

PROVIDER: S-EPMC6958728 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report.

Hongo Hiroshi H Kosaka Takeo T Aimono Eriko E Nishihara Hiroshi H Oya Mototsugu M

Diagnostic pathology 20200113 1

<h4>Background</h4>Precision medicine based on genomic analysis of germline or tumor tissue is attracting attention. However, there is no consensus on how to apply the results of genomic analysis to treatment.<h4>Case presentation</h4>A 59-year-old man diagnosed with metastatic prostate cancer was diagnosed with castration-resistant prostate cancer. Although he was sequentially treated with enzalutamide and abiraterone, bone metastasis progression was identified by skeletal scintigraphy. Therefo ...[more]

PMID: 31931827

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Project description:IntroductionThe homologous recombination repair (HRR) pathway is a frequently mutated pathway in advanced prostate cancer. The clinical course of patients with HRR gene alterations who have metastatic hormone sensitive prostate cancer (mHSPC) has not been fully characterized. Here, we examine the outcomes of men with mHSPC with HRR alterations.MethodsWe conducted a single-center retrospective analysis of men with mHSPC who underwent next generation sequencing. The primary objective was to assess the time from diagnosis of mHSPC to metastatic castrate resistance prostate cancer (mCRPC) in patients with pathogenic HRR alterations compared to individuals lacking these alterations. Key secondary objectives included time to mCRPC in prespecified cohorts, PSA response, and overall survival.Results151 men with mHSPC were identified for the study. 24% (N = 37) had pathogenic HRR gene alterations detected with the most common alterations found in BRCA2 (n = 15), ATM (n = 10), and CDK12 (n = 7). Time to mCRPC was significantly decreased in patients with HRR gene alterations versus those without such alterations (12.7 vs. 16.1 months, HR 1.95, P = .02). In multivariate analysis, the effect of HRR gene alterations on time to CRPC remained significant when adjusting for age, mHSPC therapy, the volume of disease, the presence of visceral metastases, and PSA (adjusted HR 1.69, P = .02). Stratified by specific HRR gene alteration, patients with BRCA2 or CDK12 had significantly decreased time to mCRPC compared to other HRR alterations.ConclusionHRR gene alterations are associated with the worse outcomes in mHSPC with significantly shorter time to mCRPC. Given the established role of Poly (ADP-ribose) Polymerase (PARP) inhibitors in mCRPC, these data highlight an opportunity to examine PARP inhibitors earlier in the clinical course for prostate cancer patients. Ongoing prospective studies will further validate the role of PARP inhibitors in mHSPC patients.

Dataset Information

Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report.

Publications

Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report.

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