ASCO has published an updated guideline on systemic therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), representing ASCO’s first Living Guideline in the area of prostate cancer and the first in any genitourinary (GU) cancer.1
“Guidelines will become less useful if they’re not updated continually. That one word—‘living’—is really the key to having an up-to-date, contemporary, thoughtful guideline that key opinion leaders have studied and edited every month,” said Expert Panel Co-chair Mary-Ellen Taplin, MD, FASCO, of Dana-Farber Cancer Institute and Harvard Medical School.
Innovating the Guideline Process
ASCO Living Guidelines are a new medium reserved for guidelines whose evidence is changing so rapidly that they warrant more frequent and continuous revisions than a traditional guideline process would allow.
“Living Guidelines are also more patient-centric in the sense that we are able to provide patients with the best possible care based on the most recent recommendations as compared to waiting 6 months or a year for an update to come out,” said Expert Panel Co-chair Rahul A. Parikh, MD, PhD, of the University of Kansas Medical Center.
Dr. Taplin and Dr. Parikh credited Guideline Co-author Irbaz Bin Riaz, MBBS, PhD, MS, of Mayo Clinic, in Phoenix, with helping ASCO launch the Living Guideline initiative. Dr. Riaz and his team developed a large language model that can rapidly scour the literature and report new published studies based on input criteria such as cancer type, stage, and trial design.
An Evolving Therapeutic Landscape
The ability to more quickly identify new trials and innovations in the treatment of mCRPC is critically important, given how fast the therapeutic landscape for this condition is evolving.2
For instance, in May 2025, ASCO published an update to its original guideline from 2014 on the systemic treatment of mCRPC.3 However, within a few months after that update was released, new data emerged from several phase III trials that prompted the Expert Panel to revise those recommendations. These trials included the European Organisation for Research and Treatment of Cancer 1333/PEACE-3 trial, which found that a combination of radium-223 with enzalutamide resulted in better progression-free survival and overall survival than enzalutamide alone.4 Based on this trial, the Living Guideline recommends radium-223 for select individuals with prostate-specific membrane antigen (PSMA)-negative disease or chemotherapy using cabazitaxel. Other trials that informed changes in the Living Guideline include CONTACT-02, KEYNOTE-641, and KEYNOTE-921.5-7
Mary-Ellen Taplin, MD, FASCO
Rahul A. Parikh, MD, PhD
Irbaz Bin Riaz, MBBS, PhD, MS
The Panel also re-reviewed the PSMAfore clinical trial following a recently expanded indication from the U.S. Food and Drug Administration (FDA) for the radioligand lutetium-177-PSMA-617.8,9 Consequently, the Panel recommends lutetium-177-PSMA-617 early in the treatment regimen for select patients with PSMA-positive disease.
“Within a very short period of time from our last set of guidelines, we had all of these new studies being presented—so, the purpose of this Living Guideline is to inform patients and also clinical practitioners of some of these updates that came out,” Dr. Parikh said.
He added that the Living Guideline also offers input on combination therapies to help oncologists choose appropriate treatments based on genetic markers, clinical presentation, and patient profiles.
Maximizing Utility
Although the availability of new therapies means greater hope for the more than 1.5 million men around the globe diagnosed with prostate cancer each year, it also means treatment decision-making has become “very complicated,” Dr. Taplin said.10
To ensure that the Living Guideline is maximally useful to clinicians, the authors more plainly address treatment decision-making in the context of a patient’s unique treatment history than was done in the 2014 guideline.11 Specifically, the Living Guideline lays out treatment options for patients based on whether they previously had hormone therapy, chemotherapy, an androgen receptor pathway inhibitor, or some combination of these.
“It’s somewhat of a new way to look at prostate cancer within a guideline in that it’s not just a list of choices,” Dr. Taplin said. “It’s very practical and, if used wisely, should really help practicing physicians better understand the options in front of a patient based on therapies they had before.”
Another practical aspect of the Living Guideline is its potential utility in helping oncologists sort out tough questions about treatment sequencing.
“Currently, we do not have a lot of randomized data on how to sequence some of the treatments for mCRPC. I know there are clinical trials designed to answer some of those questions, so hopefully we will soon have data to know which agents to use up front as compared to later on,” Dr. Parikh added.
‘Gray Areas,’ Diversity, and Real-World Applications
The Living Guideline also now includes information to help oncologists understand “gray areas” where the Panel lacked definitive data and thus could not give formal guidance.
For example, although not an official recommendation, the Living Guideline suggests that oncologists may want to offer cabazitaxel rather than docetaxel to certain patients, such as those with peripheral neuropathy.
Finally, the Panel included a diverse range of clinicians from various geographic regions and practice settings, as well as two patient advocates, which speaks to the Living Guideline’s representativeness.
Dr. Taplin noted that this combination of being both practical and reflective of the real world substantially adds to the value of the Living Guideline and underscores its importance for patient care.
“Metastatic prostate cancer is a terminal, life-threatening disease, and a large proportion of patients are not getting life-prolonging therapies. There are various reasons for that, but we don’t want physicians not having up-to-date information to be one of those reasons,” she said.
REFERENCES
1. Taplin M-E, Riaz IB, Rumble RB, et al: Systemic therapy in patients with metastatic castration-resistant prostate cancer: ASCO Living Guideline, Version 2026.1. J Clin Oncol January 20, 2026 (early release online).
2. Gebrael G, Ostrowski M, Agarwal N: Metastatic prostate cancer: Clinical trials to watch. Med 6(11):100927, 2025.
3. Garje R, Riaz IB, Naqvi SAA, et al: Systemic therapy in patients with metastatic castration-resistant prostate cancer: ASCO guideline update. J Clin Oncol 43:2311-2334, 2025.
4. Tombal B, Choudhury A, Saad F, et al: Results of the EORTC 1333/PEACE-3 trial. Ann Oncol. 36:1058-1067, 2025.
5. Agarwal N, Azad AA, Carles J, et al: Final analyses from a phase 3, open-label, randomised trial. Lancet Oncol 26:860-876, 2025.
6. Graff JN, Burotto M, Fong PC, et al: The randomized, double-blind, phase III KEYNOTE-641 study. Ann Oncol 36:976-987, 2025.
7. Petrylak DP, Ratta R, Matsubara N, et al: The randomized, double-blind, phase III KEYNOTE-921 trial. J Clin Oncol 43:1638-1649. 2025.
8. Morris MJ, Castellano D, Herrmann K, et al: A phase 3, randomised, controlled trial. Lancet 404:1227-1239, 2024.
9. U.S. Food and Drug Administration. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA.gov. March 28, 2025. Accessed January 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
10. McDowell S: Cancer in men: Prostate cancer is #1 for 118 countries globally. American Cancer Society. September 27, 2024. Accessed December 22, 2025. https://www.cancer.org/research/acs-research-news/prostate-cancer-is-number-1-for-118-countries-worldwide.html
11. Basch E, Loblaw DA, Oliver TK, et al: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol 32:3436-3448, 2014.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 20, 2026. All rights reserved.
