Updates on the ARANOTE Trial: PSA Response with Darolutamide Plus ADT in Patients with mHSPC

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E. David Crawford, MD, Editor of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, introduces Maha H. Hussain, MD, FACP, FASCO, Professor of Medicine and Deputy Director, Northwestern University - The Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Evanston, Illinois. In this 11-minute discussion, Dr. Crawford and Dr. Hussain discuss the evolving role of PSA nadir in treatment response and therapeutic decision-making for advanced prostate cancer, particularly in the context of the recently reported ARANOTE trial.

The ARANOTE trial evaluates the efficacy of darolutamide plus ADT compared to ADT plus placebo in over 600 patients. It reveals a stark difference in PSA nadir response rates, a robust biomarker response that correlates with delays in radiographic progression and underlines the prognostic value of PSA nadir.

While acknowledging PSA’s utility, Dr. Hussain cautions against sole reliance on it due to potential discordance with radiographic or clinical progression. She emphasizes the need for multimodal monitoring, including imaging. The discussion also touches on the rationale for intermittent androgen deprivation therapy, evolving toward the concept of treatment holidays in appropriately selected patients with excellent PSA response.

The conversation addresses how patients failing to reach a PSA nadir may benefit from therapy intensification, such as adding chemotherapy or considering targeted radiation in cases of low-volume disease. Dr. Hussain underscores a personalized, adaptive approach to treatment sequencing and combination strategies, reflecting a paradigm shift toward earlier, biomarker-informed interventions in prostate cancer treatment.
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Oncology
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