Research Letter
Abstract
Authors
Fumihiko Urano, Bess A. Marshall, Stacy Hurst, Amy Robichaux-Viehoever, Saumel Ahmadi, Tamara Hershey, Gregory Van Stavern, Paulina Cruz Bravo, Jennifer Powers Carson, John Pesko, Kelly Fox, Nathalie Erpelding, Camille L. Bedrosian
Abstract
Authors
Ryan A. Moon, Rafael Sobrano Fais, Minwoo Kim, Neal T. Vogel, Jenna B. Mendelson, Lynn M. Hartweck, John P. Carney, Melissa K. Gardner, Sally E. Prins, Sasha Z. Prisco, Tim Lahm, Kurt W. Prins
Abstract
Authors
Lawrence W. Rasmussen, Deepali Luthra, Diego Moncada-Giraldo, Crystal Lewis, Yixel M. Soto-Vazquez, Zhuo Li, Buqu Hu, Brian S. Dobosh, Delores A. Stacks, Jonathan L. Koff, Amit Gaggar, Rabindra Tirouvanziam, Camilla Margaroli
Abstract
BACKGROUND Proliferation is a key biological feature of cancer and in prostate cancer is modulated by androgen receptor (AR) signalling. Cohort studies have suggested that highly proliferative tumors respond poorly to androgen receptor pathway inhibitors (ARPIs). To clarify whether tumor proliferation interacts with treatment benefit from adding abiraterone to androgen deprivation therapy (ADT), we assessed the Ki-67 proliferation index in prostate core biopsies from participants enrolled in the STAMPEDE platform protocol. METHODS Proliferation was assessed by Ki67 immunohistochemistry on tumors from patients randomized in two sequential but non-overlapping (ie no shared controls) phase 3 trials of abiraterone or abiraterone and enzalutamide conducted in STAMPEDE (NCT00268476), with 14-year survival outcomes. A standardised unweighted global assessment method was used. Survival analyses used Cox proportional hazards models adjusted for established prognostic factors. Ki-67 was examined both continuously and dichotomised at the median. Sensitivity analyses excluded samples exposed to ADT. RESULTS Ki-67 was successfully scored on cancers from 1,605 patients. Higher Ki-67 was strongly prognostic for shorter overall survival across disease states. However, in metastatic patients treated with ADT plus abiraterone, the adverse prognostic impact of high Ki-67 was substantially attenuated (aHR=1.06 per 10-percentage-point increase), with a statistically-significant treatment-biomarker interaction (p<0.001) confirming highly proliferative tumors derived greater treatment benefit. No interaction was observed in non-metastatic disease. CONCLUSION Ki-67 is an independent prognostic biomarker in advanced prostate cancer. In metastatic disease, higher proliferation predicts greater sensitivity to abiraterone added to ADT, suggesting a potential biological vulnerability of rapidly cycling tumors to intensified AR pathway blockade. TRIAL REGISTRATION: NCT00268476
Authors
Larissa Mendes, Peter F. Dutey-Magni, Emily Grist, Ashwin Sachdeva, Sara Santos Vidal, Sharanpreet Lall, Marina A. Parry, Claire L. Amos, Nafisah B. Atako, Anna Wingate, Daniel Wetterskog, Matthew R. Sydes, Chris C. Parker, Noel Clarke, Christopher J. Sweeney, Mahesh KB Parmar, Louise C. Brown, Nicholas D. James, Daniel M. Berney, Gerhardt Attard
Abstract
Authors
Fadil M. Hannan, Mark Stevenson, Taha Elajnaf, Hussam Rostom, Kate E. Lines, Michelle Stewart, Sara Wells, Lee Moir, Thomas J. Gardella, Rajesh V. Thakker
Abstract
Authors
Jana Blazkova, Brooke D. Kennedy, Jesse S. Justement, Victoria Shi, Adeline Sewack, Maegan R. Manning, Sonali S. Dasari, Kathleen Gittens, Susan Moir, Mark Connors, Stephen A. Migueles, Tae-Wook Chun
Abstract
Authors
Bingyu Yan, Jinwoo Lee, Suhas Srinivasan, Pedro Ambriz, Quanming Shi, Diana R. Dou, Srijana Davuluri, Swarna Nandyala, Adrianne Woods, Gwendolyn Leatherman, Yanding Zhao, Roman E. Reggiardo, Manasi Sawant, Hawa Racine Thiam, Ami A. Shah, David F. Fiorentino, Lorinda S. Chung, Howard Y. Chang
Abstract
Authors
Xinyu Wang, Yung-An Huang, Anshika Sethi, Christopher Yue, Sydney Brack, Aiswarya Chattuparambil Binoy, Lauren Crowther, Carol H. Yan, Adam Deconde, Anton Kushnaryov, Andrew M. Vahabzadeh-Hagh, Jacob Husseman, Maia Little, Allyssa Strohm, Lily Jih, Jonathan J. Lyons, David H. Broide, Taylor A. Doherty
Abstract
Authors
Maiko Sezaki, Tian Li, Mingzhe Pan, Zhihong Wang, Jie Bai, Justin G. Horowitz, Julia Z. Xu, Gang Huang
Abstract
Authors
Johnathan R. Kent, Keene L. Abbott, Rachel Nordgren, Amy Deik, Nupur K. Das, Millenia Waite, Tenzin Kunchok, Anna Shevzov-Zebrun, Nathaniel Christiansen, Amir Sadek, Darren S. Bryan, Mark K. Ferguson, Jessica S. Donington, Alexander Muir, Yatrik M. Shah, Clary B. Clish, Matthew G. Vander Heiden, Maria Lucia L. Madariaga, Peggy P. Hsu
No posts were found with this tag.
Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)