The Rapidly Evolving Treatment Landscape of Metastatic Hormone-Sensitive Prostate Cancer

Front-line treatment of metastatic castration-sensitive prostate cancer (mCSPC) has become more individualized and nuanced in the last decade starting with the approval of doublet regimens based on the CHAARTED, LATITUDE, TITAN, and ARCHES trials. Triplet therapy regimens have become the mainstay in select mCSPC patients in the United States and developed countries since the results of the ARASENS and PEACE-1 trials were reported in 2022.

The ARASENS and PEACE-1 trials have clearly demonstrated that treatment intensification in the first-line setting substantially delays the development of castration resistance and improves the life expectancy of certain patients with mCSPC. Now, more than ever, it is important to consider disease volume, whether presentation with mCSPC is de novo, presence of comorbid conditions, and eligibility for docetaxel chemotherapy treatment. Currently, we are looking to further define the role of treatments currently approved for use in metastatic castration-resistant prostate cancer (mCRPC) earlier on in the disease course. We may expect radioligand therapy and PARP inhibitors to move to earlier lines of therapy in the future. However, incorporation of these treatments into existing first-line regimens may be limited by short and long-term treatment toxicities. As the first-line space continues to expand and patients live longer with mCSPC, concerns regarding the optimal sequencing of treatments will remain due to the inevitability of castration resistance and disease progression. In the future, we anticipate the development of new and effective targeted therapies that overcome the pathways of hormone resistance with the ultimate goal of helping our patients live longer and maintain a good quality of life by minimizing treatment toxicity.

Written by: Eun-mi Yu, MD & Jeanny B. Aragon-Ching, MD, GU Oncology, Inova Schar Cancer Institute, Fairfax, VA

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