Zeynep B Zengin, Nicholas C Henderson, Joseph J Park, Alicia Ali, Charles Nguyen, Clara Hwang, Pedro C Barata, Mehmet A Bilen, Laura Graham, George Mo, Deepak Kilari, Abhishek Tripathi, Matthew Labriola, Shoshana Rothstein, Rohan Garje, Vadim S Koshkin, Vaibhav G Patel, Michael T Schweizer, Andrew J Armstrong, Rana R McKay, Ajjai Alva, Tanya Dorff
{"title":"晚期前列腺癌中 AR 改变的临床意义：多机构合作。","authors":"Zeynep B Zengin, Nicholas C Henderson, Joseph J Park, Alicia Ali, Charles Nguyen, Clara Hwang, Pedro C Barata, Mehmet A Bilen, Laura Graham, George Mo, Deepak Kilari, Abhishek Tripathi, Matthew Labriola, Shoshana Rothstein, Rohan Garje, Vadim S Koshkin, Vaibhav G Patel, Michael T Schweizer, Andrew J Armstrong, Rana R McKay, Ajjai Alva, Tanya Dorff","doi":"10.1038/s41391-024-00805-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear.</p><p><strong>Methods: </strong>Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types.</p><p><strong>Results: </strong>In total, 540 CRPC patients who received ARTA and had tissue-based (n = 321) and/or blood-based (n = 244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p = 0.03). In the post-ARTA group (n = 406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%).</p><p><strong>Conclusion: </strong>In this real-world clinicogenomics database-driven study we explored the development of AR alterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":" ","pages":"378-384"},"PeriodicalIF":5.1000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106060/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration.\",\"authors\":\"Zeynep B Zengin, Nicholas C Henderson, Joseph J Park, Alicia Ali, Charles Nguyen, Clara Hwang, Pedro C Barata, Mehmet A Bilen, Laura Graham, George Mo, Deepak Kilari, Abhishek Tripathi, Matthew Labriola, Shoshana Rothstein, Rohan Garje, Vadim S Koshkin, Vaibhav G Patel, Michael T Schweizer, Andrew J Armstrong, Rana R McKay, Ajjai Alva, Tanya Dorff\",\"doi\":\"10.1038/s41391-024-00805-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear.</p><p><strong>Methods: </strong>Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types.</p><p><strong>Results: </strong>In total, 540 CRPC patients who received ARTA and had tissue-based (n = 321) and/or blood-based (n = 244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p = 0.03). In the post-ARTA group (n = 406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%).</p><p><strong>Conclusion: </strong>In this real-world clinicogenomics database-driven study we explored the development of AR alterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.</p>\",\"PeriodicalId\":20727,\"journal\":{\"name\":\"Prostate Cancer and Prostatic Diseases\",\"volume\":\" \",\"pages\":\"378-384\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106060/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostate Cancer and Prostatic Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41391-024-00805-3\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostate Cancer and Prostatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41391-024-00805-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration.
Background: AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear.
Methods: Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types.
Results: In total, 540 CRPC patients who received ARTA and had tissue-based (n = 321) and/or blood-based (n = 244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p = 0.03). In the post-ARTA group (n = 406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%).
Conclusion: In this real-world clinicogenomics database-driven study we explored the development of AR alterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.
期刊介绍：
Prostate Cancer and Prostatic Diseases covers all aspects of prostatic diseases, in particular prostate cancer, the subject of intensive basic and clinical research world-wide. The journal also reports on exciting new developments being made in diagnosis, surgery, radiotherapy, drug discovery and medical management.
Prostate Cancer and Prostatic Diseases is of interest to surgeons, oncologists and clinicians treating patients and to those involved in research into diseases of the prostate. The journal covers the three main areas - prostate cancer, male LUTS and prostatitis.
Prostate Cancer and Prostatic Diseases publishes original research articles, reviews, topical comment and critical appraisals of scientific meetings and the latest books. The journal also contains a calendar of forthcoming scientific meetings. The Editors and a distinguished Editorial Board ensure that submitted articles receive fast and efficient attention and are refereed to the highest possible scientific standard. A fast track system is available for topical articles of particular significance.
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