Prospective observational study on the relationships between genetic alterations and survival in Japanese patients with metastatic castration-sensitive prostate cancer: the impact of IDC-P.

IF 2.8 3区医学 Q3 ONCOLOGY International Journal of Clinical Oncology Pub Date : 2025-04-01 Epub Date: 2025-02-12 DOI:10.1007/s10147-025-02707-3

Masashi Kato, Hiroyuki Sato, Yushi Naito, Akiyuki Yamamoto, Hideji Kawanishi, Yojiro Nakano, Toshinori Nishikimi, Masataka Kobayashi, Atsuya Kondo, Hiroki Hirabayashi, Satoshi Katsuno, Fumitoshi Sakamoto, Tohru Kimura, Shigeki Yamamoto, Hidemori Araki, Kosuke Tochigi, Fumihiro Ito, Hatsuro Hatsuse, Naoto Sassa, Akihiro Hirakawa, Shusuke Akamatsu, Toyonori Tsuzuki

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Abstract

Background: Intraductal Carcinoma of the Prostate (IDC-P) is a significant prognostic indicator for prostate cancer, which demonstrates significant associations with homologous recombination repair gene mutations (HRRm) and alterations in tumor suppressor genes. However, no study in Japan has investigated the association between IDC-P and genetic mutations in men with metastatic castration-sensitive prostate cancer (mCSPC).

Methods: This prospective observational study enrolled 102 de novo mCSPC (LATITUDE high-risk) patients diagnosed between 2018 and 2021, with subsequent monitoring of survival outcomes. A single genitourinary pathologist evaluated all needle biopsy slides. Genetic analyses were performed using the Myriad myChoice HRD plus™. These genetic analyses covered 108 genetic loci, including 15 HRRm genes, with a success rate of 91%.

Results: Genetic alterations were observed in 79 patients (77.5%), with 20 exhibiting HRRm (19.6%). Common genetic alterations included FOXA1 (29.4%) and TP53 (17.6%) mutations; BRCA (9.8%) mutations were the most frequent HRRm (BRCA1:2 cases, BRCA2:8 cases, including 6 biallelic). IDC-P-positive patients demonstrated a significantly higher frequency of genetic aberrations (82.6% vs. 50%, p = 0.0082). Patients with biallelic BRCA2, TP53, and PTEN mutations exhibited significantly poorer cancer-specific survival. Multivariate analysis identified lactate dehydrogenase (LDH) (HR 1.005, p = 0.035), TP53 mutations (HR 5.196, p < 0.001), biallelic BRCA2 mutations (HR 10.686, p = 0.005), and IDC-P as independent predictors of poor cancer-specific survival. No cancer-related deaths occurred in IDC-P-negative cases.

Conclusion: Our study emphasizes the significant association between IDC-P and an elevated incidence of genetic alterations in Japanese mCSPC patients, emphasizing the need for early genetic testing to guide therapeutic decision-making.

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日本转移性去势敏感前列腺癌患者基因改变与生存关系的前瞻性观察研究：IDC-P的影响。

背景：前列腺导管内癌（IDC-P）是前列腺癌的重要预后指标，与同源重组修复基因突变（HRRm）和抑癌基因改变有显著相关性。然而，日本没有研究调查转移性去势敏感前列腺癌（mCSPC）患者中IDC-P与基因突变之间的关系。方法：这项前瞻性观察性研究纳入了2018年至2021年间诊断的102例新发mCSPC（纬度高危）患者，随后监测生存结果。一名泌尿生殖系统病理学家评估了所有针活检切片。使用Myriad myChoice HRD plus™进行遗传分析。这些遗传分析涵盖108个遗传位点，其中HRRm基因15个，成功率为91%。结果：遗传改变79例（77.5%），HRRm 20例（19.6%）。常见的遗传改变包括FOXA1（29.4%）和TP53（17.6%）突变；BRCA（9.8%）突变是最常见的HRRm （BRCA1:2例，BRCA2:8例，其中双等位基因6例）。idc -p阳性患者表现出更高的遗传畸变频率（82.6%比50%，p = 0.0082）。双等位基因BRCA2、TP53和PTEN突变的患者表现出明显较差的癌症特异性生存率。多变量分析确定了乳酸脱氢酶（LDH）（HR 1.005, p = 0.035）和TP53突变（HR 5.196, p）。结论：本研究强调了日本mCSPC患者中IDC-P与基因改变发生率升高之间的显著关联，强调了早期基因检测指导治疗决策的必要性。

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来源期刊

International Journal of Clinical Oncology 医学-肿瘤学

CiteScore

6.80

自引率

3.00%

发文量

175

审稿时长

2 months

期刊介绍： The International Journal of Clinical Oncology (IJCO) welcomes original research papers on all aspects of clinical oncology that report the results of novel and timely investigations. Reports on clinical trials are encouraged. Experimental studies will also be accepted if they have obvious relevance to clinical oncology. Membership in the Japan Society of Clinical Oncology is not a prerequisite for submission to the journal. Papers are received on the understanding that: their contents have not been published in whole or in part elsewhere; that they are subject to peer review by at least two referees and the Editors, and to editorial revision of the language and contents; and that the Editors are responsible for their acceptance, rejection, and order of publication.