International journal of clinical oncology · 2025
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.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Kato Masashi, Sato Hiroyuki, Naito Yushi, Yamamoto Akiyuki, Kawanishi Hideji, Nakano Yojiro, Nishikimi Toshinori, Kobayashi Masataka, Kondo Atsuya, Hirabayashi Hiroki, Katsuno Satoshi, Sakamoto Fumitoshi, Kimura Tohru, Yamamoto Shigeki, Araki Hidemori, Tochigi Kosuke, Ito Fumihiro, Hatsuse Hatsuro, Sassa Naoto, Hirakawa Akihiro, Akamatsu Shusuke, Tsuzuki Toyonori
Аннотация
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.
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.