Dr. Katherine Virgo discusses the latest evidence-based guideline recommendation updates regarding initial management of metastatic prostate cancer based on the new clinical trial results comparing triplet therapies (the addition of darolutamide, abiraterone, or enzalutamide to docetaxel plus androgen deprivation therapy) to standard of care. Dr. Virgo also discusses cost of treatment options and ongoing research questions in this field. Read the full guideline, “‘Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update” at www.asco.org/genitourinary-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/genitourinary-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.00155.  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I am interviewing Dr. Katherine Virgo from Emory University, lead author on the ‘Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update’.   Thank you for being here, Dr. Virgo.  Dr. Katherine Virgo: Thank you.  Brittany Harvey: Before we discuss this guideline, I'd just like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Virgo, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes.    So then, getting into the content of this update first, Dr. Virgo, what prompted this update to the initial management of noncastrate advanced, recurrent or metastatic prostate cancer guideline?  Dr. Katherine Virgo: The update is primarily driven by new clinical trial results comparing triplet therapies to standard of care. Triplet therapy here refers to the addition of darolutamide, abiraterone, or enzalutamide to docetaxel plus androgen deprivation therapy for patients with de novo metastatic noncastrate prostate cancer.  Brittany Harvey: Great. And then, based on this, what are the new and updated recommendations from the guideline panel?   Dr. Katherine Virgo: The first updated recommendation adds darolutamide to the list of treatment options as follows: docetaxel, abiraterone, enzalutamide, apalutamide or darolutamide, each when administered with androgen deprivation therapy, represent five separate standards of care for noncastrate metastatic prostate cancer, with the exception of the triplet therapies of docetaxel plus abiraterone plus ADT and docetaxel plus darolutamide plus ADT. The use of any of these agents in any other particular combination or in any particular series cannot yet be recommended.   The second updated recommendation states: for patients with metastatic noncastrate prostate cancer with high volume disease as defined per CHAARTED, who are candidates for treatment with chemotherapy but are unwilling or unable to receive triplet therapy, for example, due to insurance constraints, docetaxel plus ADT should be offered. We add some practical information here. Patients should be made aware that doublet therapy, docetaxel plus ADT, has inferior overall survival compared to triplet therapy, such as abiraterone and prednisone plus docetaxel plus ADT.   Then, I have a few recommendations here with respect to triplet therapy, and these are new. For patients with de novo metastatic noncastrate prostate cancer with high volume disease as defin