Distinct Response to Platinum-Based Chemotherapy among Patients with Metastatic Castration-Resistant Prostate Cancer Harboring Alterations in Genes Involved in Homologous Recombination

No AccessJournal of UrologyAdult Urology1 Sep 2021Distinct Response to Platinum-Based Chemotherapy among Patients with Metastatic Castration-Resistant Prostate Cancer Harboring Alterations in Genes Involved in Homologous Recombination Liancheng Fan, Xiaochen Fei, Yinjie Zhu, Chenfei Chi, Jiahua Pan, Jianjun Sha, Zhixiang Xin, Yiming Gong, Xinxing Du, Yanqing Wang, Baijun Dong, and Wei Xue Liancheng FanLiancheng Fan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author , Xiaochen FeiXiaochen Fei Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author , Yinjie ZhuYinjie Zhu Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author , Chenfei ChiChenfei Chi Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author , Jiahua PanJiahua Pan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Jianjun ShaJianjun Sha Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Zhixiang XinZhixiang Xin Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Yiming GongYiming Gong Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Xinxing DuXinxing Du Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Yanqing WangYanqing Wang Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Baijun DongBaijun Dong †Correspondence: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China telephone: +86 21 68383757; E-mail Address: [email protected]; E-mail Address: [email protected] Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , and Wei XueWei Xue †Correspondence: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China telephone: +86 21 68383757; E-mail Address: [email protected]; E-mail Address: [email protected] Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001819AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We aimed to explore the association between genomic status and clinical outcome of platinum-based chemotherapy among patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: We conducted a retrospective study of 55 patients with mCRPC who received platinum-based chemotherapy after the progression to docetaxel chemotherapy and underwent genomic profiling of 14 homologous recombination (HR) pathway genes. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Results: Of 55 patients, 23 harbored genomic defects in HR pathway genes. Median prostate specific antigen (PSA)-PFS for the HR defect group was 6.7 months compared with 2.6 months for the no HR defect group (p=0.001). The patients harboring somatic HR defect displayed shorter PSA-PFS than those harboring germline HR defect (4.5 months vs not available; p=0.066). The PSA50 (patients who survived for 12 weeks and had a PSA decline over 50% from baseline) response rate displayed higher in patients harboring BRCA2 or ATM defect (6/8, 75.0%) than in those harboring CDK12 defect (2/9, 22.2%; p=0.06). Patients harboring BRCA2 or ATM defect displayed prolonged PSA-PFS, compared with those harboring CDK12 defect and those harboring other HR defect (p=0.038). In multivariate Cox regression analysis, HR defect and BRCA2 or ATM defect were independent significant factors associated with superior PAS-PFS to platinum-based chemotherapy. Conclusions: The patients with mCRPC harboring alterations in different HR genes displayed distinct response to platinum-based chemotherapy. Patients with mCRPC harboring genomic defects in crucial HR genes either in the germline or somatic, especially BRCA2 and ATM, might experience superior outcomes to platinum-based chemotherapy, compared with those harboring CDK12 defect. References 1. : Prostate cancer, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2019; 17: 479. 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Google Scholar Supported by the National Institutes of Health, National Natural Science Foundation of China (81572536, 81672850, 81772742, 81702840, 81702542, 81972578, 81902863, 82002710), Science and Technology Commission of Shanghai Municipality (19411967400, 19ZR1431000, 19XD1402300, 19YF1428400), Shanghai Municipal Health Commission (201640247, 2019LJ11), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20152215, 20191906), Shanghai Jiao Tong University (YG2016ZD08, YG2017MS47, YG2017MS52); Innovation Fund for Translational Research of Shanghai Jiao Tong University School of Medicine (TM201907), Shanghai Sailing Program (20YF1425300) and Incubating Program for Clinical Research and Innovation of Renji Hospital Shanghai Jiao Tong University School of Medicine (PYZY 16-008, PYXJS16-015, RJZZ19-17). © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue 3September 2021Page: 630-637Supplementary Materials Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Keywordsprostatic neoplasms, castration-resistantdrug therapyhomologous recombinationDNA damageAcknowledgmentsWe thank Tingting Zhao, Fangqin Wang, Yiqun Zhang and Yining Yang, who gave strong support to the present study.MetricsAuthor Information Liancheng Fan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Xiaochen Fei Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Yinjie Zhu Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Chenfei Chi Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Jiahua Pan Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Jianjun Sha Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Zhixiang Xin Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Yiming Gong Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Xinxing Du Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Yanqing Wang Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Baijun Dong Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China †Correspondence: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China telephone: +86 21 68383757; E-mail Address: [email protected]; E-mail Address: [email protected] More articles by this author Wei Xue Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China †Correspondence: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China telephone: +86 21 68383757; E-mail Address: [email protected]; E-mail Address: [email protected] More articles by this author Expand All Supported by the National Institutes of Health, National Natural Science Foundation of China (81572536, 81672850, 81772742, 81702840, 81702542, 81972578, 81902863, 82002710), Science and Technology Commission of Shanghai Municipality (19411967400, 19ZR1431000, 19XD1402300, 19YF1428400), Shanghai Municipal Health Commission (201640247, 2019LJ11), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20152215, 20191906), Shanghai Jiao Tong University (YG2016ZD08, YG2017MS47, YG2017MS52); Innovation Fund for Translational Research of Shanghai Jiao Tong University School of Medicine (TM201907), Shanghai Sailing Program (20YF1425300) and Incubating Program for Clinical Research and Innovation of Renji Hospital Shanghai Jiao Tong University School of Medicine (PYZY 16-008, PYXJS16-015, RJZZ19-17). 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