Multi-institutional Analysis of Metastasis-directed Therapy with or Without Androgen Deprivation Therapy in Oligometastatic Castration-sensitive Prostate Cancer

Matthew P Deek; Philip Sutera; Yuezhou Jing; Robert Gao; Emily Rothman; Heather Day; David Chang; Piet Dirix; Andrew J Armstrong; Bethany Campbell; Fernando Lopez Campos; Miguel Berenguer; Matthew Ramotar; Antonio Conde-Moreno; Alejandro Berlin; Davide Giovanni Bosetti; Niall Corcoran; Bridget Koontz; Carole Mercier; Shankar Siva; David Pryor; Piet Ost; Mai Anh Huynh; Stephanie Kroeze; Bradley Stish; Ana Kiess; Bruce Trock; Phuoc T Tran; Silke Gillessen; Christopher Sweeney

doi:10.1016/j.euo.2024.03.010

Multi-institutional Analysis of Metastasis-directed Therapy with or Without Androgen Deprivation Therapy in Oligometastatic Castration-sensitive Prostate Cancer

Eur Urol Oncol. 2024 Apr 2:S2588-9311(24)00086-5. doi: 10.1016/j.euo.2024.03.010. Online ahead of print.

Authors

Matthew P Deek¹, Philip Sutera², Yuezhou Jing³, Robert Gao⁴, Emily Rothman⁵, Heather Day⁶, David Chang⁷, Piet Dirix⁸, Andrew J Armstrong⁹, Bethany Campbell¹⁰, Fernando Lopez Campos¹¹, Miguel Berenguer¹², Matthew Ramotar¹³, Antonio Conde-Moreno¹², Alejandro Berlin¹², Davide Giovanni Bosetti¹⁴, Niall Corcoran¹⁰, Bridget Koontz¹⁵, Carole Mercier⁸, Shankar Siva⁷, David Pryor⁶, Piet Ost¹⁶, Mai Anh Huynh⁵, Stephanie Kroeze¹⁷, Bradley Stish⁴, Ana Kiess², Bruce Trock³, Phuoc T Tran¹⁸, Silke Gillessen¹⁴, Christopher Sweeney¹⁹

Affiliations

¹ Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
² Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ The James Buchanan Brady Urological Institute of Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Radiation Oncology, The Mayo Clinic, Rochester, MN, USA.
⁵ Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
⁶ Department of Radiation Oncology, Australian Prostate Cancer Research Center, Queensland, Australia.
⁷ Department of Radiation Oncology, Peter MacCallum Cancer Centre, Victoria, Australia.
⁸ Department of Radiation-Oncology, GasthuisZusters Antwerp (GZA) 'Sisters of the Hospital', Antwerp, Belgium.
⁹ Department of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University Medical Center, Durham, NC, USA.
¹⁰ Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia.
¹¹ Department of Radiation Oncology, Hospital Ramón y Cajal, Madrid, Spain.
¹² Radiation Oncology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
¹³ Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
¹⁴ Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland.
¹⁵ GenesisCare US, Fort Myers, FL, USA.
¹⁶ Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
¹⁷ Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.
¹⁸ Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁹ South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia. Electronic address: christopher.sweeney@adelaide.edu.au.

PMID: 38570239
DOI: 10.1016/j.euo.2024.03.010

Abstract

Background: Metastasis-directed therapy (MDT) is increasingly being used in oligometastatic castration-sensitive prostate cancer (omCSPC). However, it is currently unclear how to optimally integrate MDT with the standard of care of systemic hormonal therapy.

Objective: To report long-term outcomes of MDT alone versus MDT and a defined course of androgen deprivation therapy (ADT) in omCSPC.

Design, setting, and participants: Here, a multicenter, international retrospective cohort of omCSPC as defined by conventional imaging was reported.

Outcome measurements and statistical analysis: Biochemical progression-free survival (bPFS), distant progression-free survival (dPFS), and combined biochemical or distant progression-free survival (cPFS) were evaluated with Kaplan-Meier and multivariable Cox proportional hazard regression models.

Results and limitations: A total of 263 patients were included, 105 with MDT + ADT and 158 with MDT alone. The majority of patients had metachronous disease (90.5%). Five-year bPFS, dPFS, and cPFS were, respectively, 24%, 41%, and 19% in patients treated with MDT + ADT and 11% (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.36-0.64), 29% (HR 0.56, 95% CI 0.40-0.78), and 9% (HR 0.50, 95% CI 0.38-0.67) in patients treated with MDT alone. On a multivariable analysis adjusting for pretreatment variables, the use of ADT was associated with improved bPFS (HR 0.43, p < 0.001), dPFS (HR 0.45, p = 0.002), and cPFS (HR 0.44, p < 0.001).

Conclusions: In this large multi-institutional report, the addition of concurrent ADT to MDT appears to improve time to prostate-specific antigen progression and distant recurrence, noting that about 10% patients had durable control with MDT alone. Ongoing phase 3 studies will help further define treatment options for omCSPC.

Patient summary: Here, we report a large retrospective review evaluating the outcomes of metastasis-directed therapy with or without a limited course of androgen deprivation for patients with oligometastatic castration-sensitive prostate cancer. This international multi-institutional review demonstrates that the addition of androgen deprivation therapy to metastasis-directed therapy (MDT) improves progression-free survival. While a proportion of patients appear to have long-term disease control with MDT alone, further work in biomarker discovery is required to better identify which patients would be appropriate for de-escalated therapy.

Keywords: Androgen deprivation therapy; Castration-sensitive prostate cancer; Metastasis-directed therapy; Oligometastatic.