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Review
. 2023 Jul 10;41(20):3584-3590.
doi: 10.1200/JCO.23.00723. Epub 2023 Jun 2.

Early Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer

Affiliations
Review

Early Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer

Jeremiah Wala et al. J Clin Oncol. .

Abstract

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.For generations, oncologists and urologists have used androgen deprivation therapy (ADT) to manage metastatic hormone-sensitive prostate cancer (mHSPC). Until recently, ADT monotherapy was standard. Within the past decade, a series of trials have clearly demonstrated improved outcomes with a more aggressive up-front approach. Doublet intensification therapy, involving either ADT plus docetaxel or ADT plus any of several second-generation oral androgen-receptor pathway inhibitors (ARPIs), provide considerable survival advantages compared with ADT alone. In 2022, two trials, PEACE-1 and ARASENS, demonstrated the potential of triplet therapy, adding an ARPI to an ADT-docetaxel doublet. In the Original Report that accompanies this article, the authors provide a post hoc analysis of ARASENS (ADT plus docetaxel, with or without darolutamide), identifying the subpopulations of patients with mHSPC who might benefit most from a triplet regimen. They segment the ARASENS cohort by disease volume and disease risk profile, finding that triplet therapy is associated with improved outcomes regardless of category (although with limited power in the low-volume cohort). Meanwhile, trials are ongoing examining the role of radiotherapy (RT) in mHSPC, a modality previously reserved for localized disease or isolated, symptomatic metastases. Here, we present a mHSPC case and discuss our approach to mHSPC considering recent studies. We recommend triplet therapy for patients who are suitable candidates for chemotherapy, especially for patients with high-volume disease. We also favor aggressive use of RT, when feasible, for patients with low-volume mHSPC.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Mark Pomerantz

Honoraria: Bayer

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Proposed algorithm for determining treatment intensification regimen for mHSPC. ADT, androgen deprivation therapy; mHSPC, metastatic hormone-sensitive prostate cancer; PSA, prostate-specific antigen; RT, radiotherapy.

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