Genomic Predictors of Response to Metastasis-directed Therapy With or Without Androgen Deprivation Therapy

Philip Sutera¹, Kim Van der Eecken², Yang Song³, Amol C Shetty³, Elai Davicioni⁴, James A Proudfoot⁴, Alexander Hakansson⁴, Keara English¹, Jarey Wang¹, Ozan Cem Guler⁵, Soha Bazyar⁶, Sofie Verbeke⁷, Jo Van Dorpe², Valérie Fonteyne⁸, Bram De Laere⁸, Lara Hathout⁹, Ronald Ennis⁹, Salma K Jabbour⁹, Biren Saraiya¹⁰, Ryan Stephenson¹⁰, Tina Mayer¹⁰, Mark Mishra⁶, Zaker Rana⁶, Jason Molitoris⁶, Ana Kiess¹, Daniel Y Song¹, Theodore DeWeese¹, Kenneth J Pienta¹¹, Phuoc T Tran⁶, Alejandro Berlin¹², Cem Onal⁵, Piet Ost⁸, Matthew P Deek¹³

Affiliations

¹ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Departments of Pathology and Human Structure and Repair, Ghent University, Ghent, Belgium.
³ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Veracyte, San Diego, CA, USA.
⁵ Department of Radiation Oncology, Baskent University, Ankara, Turkey.
⁶ Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁷ Department of Pathology and Cancer Research Institute, Ghent University Hospital, Ghent, Belgium.
⁸ Department of Radiation Oncology, Ghent University Hospital, Belgium.
⁹ Department of Radiation Oncology, Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, USA.
¹⁰ Division of Medical Oncology, Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, USA.
¹¹ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹² Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
¹³ Department of Radiation Oncology, Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, USA. Electronic address: matthewdeek@gmail.com.

PMID: 40976747
DOI: 10.1016/j.euo.2025.07.007

Free article

Genomic Predictors of Response to Metastasis-directed Therapy With or Without Androgen Deprivation Therapy

Philip Sutera et al. Eur Urol Oncol. 2025.

Free article

. 2025 Sep 20:S2588-9311(25)00199-3.

doi: 10.1016/j.euo.2025.07.007. Online ahead of print.

Authors

Affiliations

¹ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Departments of Pathology and Human Structure and Repair, Ghent University, Ghent, Belgium.
³ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Veracyte, San Diego, CA, USA.
⁵ Department of Radiation Oncology, Baskent University, Ankara, Turkey.
⁶ Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁷ Department of Pathology and Cancer Research Institute, Ghent University Hospital, Ghent, Belgium.
⁸ Department of Radiation Oncology, Ghent University Hospital, Belgium.
⁹ Department of Radiation Oncology, Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, USA.
¹⁰ Division of Medical Oncology, Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, USA.
¹¹ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹² Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
¹³ Department of Radiation Oncology, Rutgers Cancer Institute, Rutgers University, New Brunswick, NJ, USA. Electronic address: matthewdeek@gmail.com.

PMID: 40976747
DOI: 10.1016/j.euo.2025.07.007

Abstract

Metastasis-directed therapy (MDT) is an emerging treatment option for metachronous oligometastatic castration-sensitive prostate cancer (omCSPC) and can delay time to progression and the need to initiate androgen deprivation therapy (ADT). However, optimal ways to synergize MDT and ADT are not known, and better personalization of MDT is needed. We examined the role of combined ADT and MDT and the ability of genomic alterations to provide prognostic and predictive information regarding response to MDT. We found that high-risk (HiRi) mutations in TP53, BRCA1/2, ATM, and Rb1 are poor prognostic markers in omCSPC. In addition, patients harboring HiRi mutations experienced greater benefit from addition of ADT to MDT, indicating that these alterations are predictive biomarkers for treatment intensification. Our results suggest that genetic biomarkers might aid in treatment personalization for patients with omCSPC.

Keywords: Castration-sensitive prostate cancer; Genomics; Metastasis-directed therapy; Oligometastasis; Personalized medicine.

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Genomic Predictors of Response to Metastasis-directed Therapy With or Without Androgen Deprivation Therapy

Affiliations

Genomic Predictors of Response to Metastasis-directed Therapy With or Without Androgen Deprivation Therapy

Authors

Affiliations

Abstract

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous