Early Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer

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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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