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Survival outcomes of real world patients with metastatic hormone-sensitive prostate cancer who do not achieve optimal PSA response with intensified androgen deprivation therapy with docetaxel or androgen receptor pathway inhibitors

Prostate Cancer and Prostatic Diseases (2023)Cite this article

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A Correction to this article was published on 24 August 2023

This article has been updated

Abstract

Introduction

In patients with metastatic hormone-sensitive prostate cancer (mHSPC) undergoing intensified androgen deprivation therapy (ADT), not achieving an optimal PSA response, defined as PSA nadir >0.2 ng/ml (PSAsubOR) has been associated with worse survival outcomes in clinical trials (1)(10)(11). Here, we externally evaluate, the impact of optimal PSA response on survival outcomes in these patients and provide absolute PFS and OS measures in those with PSAsubOR in the context of ADT intensification in real world setting.

Methods

In this retrospective study, all consecutive patients with mHSPC who underwent intensified ADT treated at our institution, and whose outcomes data were available, were included. We classified patients based on their PSA nadir on treatment: those with a on treatment PSAOR (PSA nadir ≤0.2 ng/ml) versus PSAsubOR.

Results

A total of 205 patients were eligible: 136 (66.3%) patients achieved PSAOR versus 69 (33.7%) patients had PSAsubOR. Patients who experienced a PSAOR had significantly improved PFS and OS from the start of intensified ADT versus who did not: PFS was not reached (NR) versus 11 months (hazard ratio (HR) 0.20, P < 0.001) and OS was NR versus 38.9 months (HR 0.21, P < 0.001). Survival outcomes were poor with PSAsubOR regardless of intensification with docetaxel or an ARPI (absolute PFS and OS measures for each group are provided in the text).

Conclusion

Our study is the first to explore the negative impact of PSAsubOR in patients with mHSPC undergoing intensified ADT in the real-world setting, and is the first to provide absolute PFS and OS in patients with PSAsubOR receiving ADT intensification with ARPIs or docetaxel outside of clinical trial setting. These data will aid with prognostication, patient counseling, and for designing future clinical trials for patients with PSAsubOR.

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Fig. 1: Survival Analysis.

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Data availability

The data generated in this study are not publicly available as they could compromise patient privacy but are available upon reasonable request from the corresponding author.

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Author notes

  1. These authors contributed equally: Georges Gebrael, Nicolas Sayegh, Vinay Mathew Thomas.

Authors and Affiliations

  1. Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Georges Gebrael, Nicolas Sayegh, Vinay Mathew Thomas, Beverly Chigarira, Nishita Tripathi, Yeon Jung Jo, Haoran Li, Kamal Kant Sahu, Ayana Srivastava, Taylor McFarland, Benjamin L. Maughan, Umang Swami & Neeraj Agarwal

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  1. Georges Gebrael
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Contributions

Study concept and design: GG, NS, VMT, BLM, US, NA. Acquisition of data: GG, NS, VMT, NT, HL, KKS, AS2, TM, BLM, US, NA. Analysis and interpretation of data: GG, NS, VMT, BC, YJ, US, NA. Drafting of the manuscript: GG, NS, VMT. Critical revision of the manuscript for important intellectual content: GG, NS, VMT, NT, BLM, US, NA. Supervision: US, NA.

Corresponding author

Correspondence to Neeraj Agarwal.

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Competing interests

Neeraj Agarwal, MD: NA does not report any personal COI since April 15, 2021. However, the following are his lifetime personal COIs: Consultancy to Astellas, Astra Zeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics. Research funding to Neeraj Agarwal’s institution: Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Umang Swami, MD: has been paid for a consulting or advisory role by Seattle Genetics, Astellas Pharma, Exelixis, Imvax, and AstraZeneca, currently or during the past 2 years. Dr. Swami’s institution has received research funding from Janssen, Seattle Genetics/Astellas, and Exelixis, currently or within the past 2 years. Benjamin L. Maughan, MD: is a paid consultant/advisor to Abbvie, Pfizer, AVEO oncology, Janssen, Astellas, Bristol-Myers Squibb, Clovis, Tempus, Merck, Exelixis, Bayer Oncology and Peloton Therapeutics; Huntsman Cancer Institute has received research funding from Exelixis (Inst), Bavarian-Nordic (Inst), Clovis (Inst), Genentech (Inst) and Bristol-Myers Squibb (Inst) on his behalf.

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Gebrael, G., Sayegh, N., Thomas, V.M. et al. Survival outcomes of real world patients with metastatic hormone-sensitive prostate cancer who do not achieve optimal PSA response with intensified androgen deprivation therapy with docetaxel or androgen receptor pathway inhibitors. Prostate Cancer Prostatic Dis (2023). https://doi.org/10.1038/s41391-023-00696-w

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