Genomic mutations and homologous recombination deficiency (HRD) score in Japanese patients with metastatic hormone-sensitive prostate cancer (mHSPC): The impact of intraductal carcinoma of the prostate (IDC-P).

Authors

null

Masashi Kato

Nagoya University Graduate School of Medicine, Nagoya, Japan

Masashi Kato , Akiyuki Yamamoto , Hideji Kawanishi , Yushi Naito , Shusuke Akamatsu , Toyonori Tsuzuki

Organizations

Nagoya University Graduate School of Medicine, Nagoya, Japan, Toyohashi Municipal Hospital, Toyohashi, Japan, Department of Urology, Aichi Medical University Hospital, Nagakute, Japan, Department of Urology, Nagoya University Hospital, Nagoya, Japan, Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan, Aichi Medical University, Nagakute, Japan

Research Funding

Astra Zeneca

Background: Intraductal carcinoma of the prostate (IDC-P) is a significant prognostic factor associated with adverse clinical outcomes. A recent study has revealed significant associations between IDC-P and germline homologous recombination repair gene mutations (HRRm) and alterations in tumor suppressor genes. However, no study has investigated the association between IDC-P and gene mutations in a Japanese population. We evaluated the association between IDC-P in prostate core needle biopsies and gene mutations in metastatic hormone-sensitive prostate cancer (mHSPC) in a Japanese population. Methods: This study enrolled 102 mHSPC patients, classified as LATITUDE high-risk, diagnosed between 2018 and 2021 in Nagoya University and affiliated hospitals, all within three years of diagnosis, and with informed consent. Initial screening identified 106 patients with gene mutation data; four were excluded due to inadequate metastatic lesions or insufficient biopsy number. A single genitourinary pathologist assessed all biopsy slides according to 2019 ISUP grading system. Furthermore, the genetic analysis involved the examination of 108 genes using the Myriad myChoice HRD plus assay, alongside HRD (Homologous recombination deficiency) score analysis. Results: Our study achieved a 91% success rate in genomic testing. In total, 20 (19.6%) and 73 patients (71.6%) exhibited HRRm and molecular alterations in pathway other than HRR (MAOT-HRR), respectively. Notably, common HRRm included BRCA (n = 10; BRCA 1:2, BRCA 2:8) and CDK12 (n = 6) mutations, whereas common MAOT-HRR included FOXA1 (n = 30) and TP53 (n = 18) mutations. MAOT-HRR were more common in IDC-P positive patients (75.6% vs. 50%, p=0.06). PTEN and TP53 mutations were notably enriched in IDC-P positive patients (PTEN: 5.8% vs. 0%, TP53: 20.9% vs. 0%, p=0.06). Patients with IDC-P exhibited higher HRD scores (21.3 ± 8.8 vs. 16.6 ± 8.6, p = 0.06) compared to those without IDC-P, with CDK12 and BRCA mutations being more common in this group (CDK12: 7.0% vs 0%, BRCA: 10.5% vs 6.3%). In addition, the frequency of HRRm was slightly higher in patients with IDC-P compared to those without IDC-P (21% vs. 12.5%, p = 0.73). Finally, the frequency of genetic alterations (HRRm or MAOT-HRR) was significantly higher in patients with IDC-P positive patients (82.6% vs. 50%, p=0.0082). Conclusions: Among Japanese mHSPC patients, IDC-P demonstrates significant associations with an elevated incidence of genetic alterations and increased HRD score, emphasizing its potential clinical significance.

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Abstract Details

Meeting

2024 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer - Advanced,Prostate Cancer - Localized

Sub Track

Translational Research, Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 42, 2024 (suppl 4; abstr 195)

DOI

10.1200/JCO.2024.42.4_suppl.195

Abstract #

195

Poster Bd #

J3

Abstract Disclosures

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