Umang Swami1, Pedro Isaacsson Velho2, Roberto Nussenzveig1, Jonathan Chipman3, Victor Sacristan Santos4, Stephanie Erickson5, Divya Dharmaraj6, Ajjai Shivaram Alva5, Ulka N Vaishampayan6, John Esther1, Andrew W Hahn7, Benjamin Louis Maughan1, Emmanuel S Antonarakis8, Neeraj Agarwal9. 1. Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. 2. Sidney Kimmel Comprehensive Cancer Center, John Hopkins University, Baltimore, MD, USA. 3. Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA; Cancer Biostatistics Shared Resource, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. 4. Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain. 5. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. 6. Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. 7. Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA. 8. Sidney Kimmel Comprehensive Cancer Center, John Hopkins University, Baltimore, MD, USA. Electronic address: eantona1@jhmi.edu. 9. Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Electronic address: neeraj.agarwal@hci.utah.edu.
Abstract
Recently, mutations in speckle-type pox virus and zinc finger protein (SPOP) gene (mutant SPOP [mtSPOP]) have been associated with improved outcomes to abiraterone in the castration-resistant setting. We hypothesized that mtSPOP would be associated with improved outcomes to systemic therapy in men with de novo metastatic castration-sensitive prostate cancer (d-mCSPC). Retrospective data of newly diagnosed d-mCSPC patients were collected from four institutions. Eligibility criteria included standard androgen deprivation therapy without intensification, and SPOP mutational status (mtSPOP or wild-type SPOP [wtSPOP]) determination by targeted next-generation sequencing from tumor biopsies. A total of 121 men (25 mtSPOP [21%] and 96 wtSPOP [79%]) were included. After adjusting for covariates, mtSPOP was significantly associated with better median progression-free survival (35 vs 13 mo; adjusted hazard ratio [HR] 0.47; p = 0.016) and overall survival (97 vs 69 mo; adjusted HR 0.32; p = 0.027), with similar HR and p value on the univariate analysis. These findings, upon external validation, may assist with counseling and prognostication in the clinic, and inform the design of future clinical trials in this setting. PATIENT SUMMARY: : Presence of tumor mutation in speckle-type pox virus and zinc finger protein (SPOP) gene was associated with improved survival outcomes in men with de novo metastatic castration-sensitive prostate cancer receiving standard androgen deprivation therapy.
Recently, mutations in speckle-type pox virus and zinc finger protein (SPOP) gene (mutant SPOP [mtSPOP]) have been associated with improved outcomes to abiraterone in the castration-resistant setting. We hypothesized that mtSPOP would be associated with improved outcomes to systemic therapy in men with de novo metastatic castration-sensitive prostate cancer (d-mCSPC). Retrospective data of newly diagnosed d-mCSPC patients were collected from four institutions. Eligibility criteria included standard androgen deprivation therapy without intensification, and SPOP mutational status (mtSPOP or wild-type SPOP [wtSPOP]) determination by targeted next-generation sequencing from tumor biopsies. A total of 121 men (25 mtSPOP [21%] and 96 wtSPOP [79%]) were included. After adjusting for covariates, mtSPOP was significantly associated with better median progression-free survival (35 vs 13 mo; adjusted hazard ratio [HR] 0.47; p = 0.016) and overall survival (97 vs 69 mo; adjusted HR 0.32; p = 0.027), with similar HR and p value on the univariate analysis. These findings, upon external validation, may assist with counseling and prognostication in the clinic, and inform the design of future clinical trials in this setting. PATIENT SUMMARY: : Presence of tumor mutation in speckle-type pox virus and zinc finger protein (SPOP) gene was associated with improved survival outcomes in men with de novo metastatic castration-sensitive prostate cancer receiving standard androgen deprivation therapy.
Authors: Christopher E Barbieri; Sylvan C Baca; Michael S Lawrence; Francesca Demichelis; Mirjam Blattner; Jean-Philippe Theurillat; Thomas A White; Petar Stojanov; Eliezer Van Allen; Nicolas Stransky; Elizabeth Nickerson; Sung-Suk Chae; Gunther Boysen; Daniel Auclair; Robert C Onofrio; Kyung Park; Naoki Kitabayashi; Theresa Y MacDonald; Karen Sheikh; Terry Vuong; Candace Guiducci; Kristian Cibulskis; Andrey Sivachenko; Scott L Carter; Gordon Saksena; Douglas Voet; Wasay M Hussain; Alex H Ramos; Wendy Winckler; Michelle C Redman; Kristin Ardlie; Ashutosh K Tewari; Juan Miguel Mosquera; Niels Rupp; Peter J Wild; Holger Moch; Colm Morrissey; Peter S Nelson; Philip W Kantoff; Stacey B Gabriel; Todd R Golub; Matthew Meyerson; Eric S Lander; Gad Getz; Mark A Rubin; Levi A Garraway Journal: Nat Genet Date: 2012-05-20 Impact factor: 38.330
Authors: Chuandong Geng; Kimal Rajapakshe; Shrijal S Shah; John Shou; Vijay Kumar Eedunuri; Christopher Foley; Warren Fiskus; Mahitha Rajendran; Sue Anne Chew; Martin Zimmermann; Richard Bond; Bin He; Cristian Coarfa; Nicholas Mitsiades Journal: Cancer Res Date: 2014-10-01 Impact factor: 12.701
Authors: Chuandong Geng; Bin He; Limei Xu; Christopher E Barbieri; Vijay Kumar Eedunuri; Sue Anne Chew; Martin Zimmermann; Richard Bond; John Shou; Chao Li; Mirjam Blattner; David M Lonard; Francesca Demichelis; Cristian Coarfa; Mark A Rubin; Pengbo Zhou; Bert W O'Malley; Nicholas Mitsiades Journal: Proc Natl Acad Sci U S A Date: 2013-04-04 Impact factor: 11.205
Authors: Dan Robinson; Eliezer M Van Allen; Yi-Mi Wu; Nikolaus Schultz; Robert J Lonigro; Juan-Miguel Mosquera; Bruce Montgomery; Mary-Ellen Taplin; Colin C Pritchard; Gerhardt Attard; Himisha Beltran; Wassim Abida; Robert K Bradley; Jake Vinson; Xuhong Cao; Pankaj Vats; Lakshmi P Kunju; Maha Hussain; Felix Y Feng; Scott A Tomlins; Kathleen A Cooney; David C Smith; Christine Brennan; Javed Siddiqui; Rohit Mehra; Yu Chen; Dana E Rathkopf; Michael J Morris; Stephen B Solomon; Jeremy C Durack; Victor E Reuter; Anuradha Gopalan; Jianjiong Gao; Massimo Loda; Rosina T Lis; Michaela Bowden; Stephen P Balk; Glenn Gaviola; Carrie Sougnez; Manaswi Gupta; Evan Y Yu; Elahe A Mostaghel; Heather H Cheng; Hyojeong Mulcahy; Lawrence D True; Stephen R Plymate; Heidi Dvinge; Roberta Ferraldeschi; Penny Flohr; Susana Miranda; Zafeiris Zafeiriou; Nina Tunariu; Joaquin Mateo; Raquel Perez-Lopez; Francesca Demichelis; Brian D Robinson; Marc Schiffman; David M Nanus; Scott T Tagawa; Alexandros Sigaras; Kenneth W Eng; Olivier Elemento; Andrea Sboner; Elisabeth I Heath; Howard I Scher; Kenneth J Pienta; Philip Kantoff; Johann S de Bono; Mark A Rubin; Peter S Nelson; Levi A Garraway; Charles L Sawyers; Arul M Chinnaiyan Journal: Cell Date: 2015-05-21 Impact factor: 41.582
Authors: Wassim Abida; Joanna Cyrta; Glenn Heller; Davide Prandi; Joshua Armenia; Ilsa Coleman; Marcin Cieslik; Matteo Benelli; Dan Robinson; Eliezer M Van Allen; Andrea Sboner; Tarcisio Fedrizzi; Juan Miguel Mosquera; Brian D Robinson; Navonil De Sarkar; Lakshmi P Kunju; Scott Tomlins; Yi Mi Wu; Daniel Nava Rodrigues; Massimo Loda; Anuradha Gopalan; Victor E Reuter; Colin C Pritchard; Joaquin Mateo; Diletta Bianchini; Susana Miranda; Suzanne Carreira; Pasquale Rescigno; Julie Filipenko; Jacob Vinson; Robert B Montgomery; Himisha Beltran; Elisabeth I Heath; Howard I Scher; Philip W Kantoff; Mary-Ellen Taplin; Nikolaus Schultz; Johann S deBono; Francesca Demichelis; Peter S Nelson; Mark A Rubin; Arul M Chinnaiyan; Charles L Sawyers Journal: Proc Natl Acad Sci U S A Date: 2019-05-06 Impact factor: 11.205
Authors: Mari Nakazawa; Mike Fang; Catherine H Marshall; Tamara L Lotan; Pedro Isaacsson Velho; Emmanuel S Antonarakis Journal: Prostate Date: 2021-11-15 Impact factor: 4.104
Authors: Philip Sutera; Matthew P Deek; Kim Van der Eecken; Alexander W Wyatt; Amar U Kishan; Jason K Molitoris; Matthew J Ferris; M Minhaj Siddiqui; Zaker Rana; Mark V Mishra; Young Kwok; Elai Davicioni; Daniel E Spratt; Piet Ost; Felix Y Feng; Phuoc T Tran Journal: Prostate Date: 2022-08 Impact factor: 4.012
Authors: Fadi Taza; Albert E Holler; Wei Fu; Hao Wang; Nabil Adra; Costantine Albany; Ryan Ashkar; Heather H Cheng; Alexandra O Sokolova; Neeraj Agarwal; Adam Kessel; Alan Bryce; Nellie Nafissi; Pedro Barata; A Oliver Sartor; Diogo Bastos; Oren Smaletz; Jacob E Berchuck; Mary-Ellen Taplin; Rahul Aggarwal; Cora N Sternberg; Panagiotis J Vlachostergios; Ajjai S Alva; Christopher Su; Catherine H Marshall; Emmanuel S Antonarakis Journal: JCO Precis Oncol Date: 2021-07-22