The management of metastatic (CRPC) has rapidly accelerated in the past decade, giving oncologists a wider range of tools to work with and patients new opportunities for improving survival and maintaining quality of life. These significant advancements have prompted ASCO to release a guideline update on the systemic treatment of metastatic CRPC.1
“Use of these [updated] guidelines can lead to improved patient outcomes, better survival, and more efficient use of health-care resources,” said Expert Panel Co-Chair Rohan Garje, MD, of Miami Cancer Institute, Baptist Health South Florida.
Rohan Garje, MD
The updated guideline, titled “Systemic Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update,” was published in the Journal of Clinical Oncology.1 This guideline used a living systematic review on systemic treatment options for metastatic CRPC as the evidence base on which the recommendations were made.2
Keeping Pace With Progress in the Field
Prostate cancer accounts for more than 33,000 deaths per year in the United States, making it the second deadliest cancer among U.S. males.3 In particular, metastatic CRPC remains a challenging diagnosis, because most patients will develop resistance to androgen-deprivation therapy and often experience relapse on systemic treatment.4
Although curative treatment of advanced disease does not exist, the past decade has seen significant improvement in the understanding of genomics and biological mechanisms undergirding metastatic CRPC.4 As a result, treatments and approaches to disease management are expanding. This includes new treatment options (eg, PARP inhibitors, chemotherapy with cabazitaxel, and immunotherapy) as well as more intensified treatments that use doublet or triplet combinations.
“There is a lot of heterogeneity in how patients are treated for castration-sensitive prostate cancer, and that affects how we treat and evaluate patients for castrate-resistant prostate cancer,” said Expert Panel Co-Chair Rahul A. Parikh, MBBS, PhD, of the University of Kansas Medical Center.
Rahul A. Parikh, MBBS, PhD
To ensure oncologists have a better understanding of the evolving treatment landscape, ASCO convened an Expert Panel to assess the literature. This represented the first full update of the guideline since its original publication in 2014.5 An Expert Panel conducted two rapid updates in 2022 and 2023, but they were largely focused on new data concerning the radioligand therapy lutetium-177–labeled PSMA-617 (LuPSMA).6,7 Furthermore, unlike the original guideline and its previous focused updates, this broad update offers recommendations based on a patient’s previous treatment.
“The systematic review informing the guideline was conducted using the ‘living’ interactive evidence synthesis framework,” Dr. Garje said. “This framework will enable us to regularly update the guidelines with timely revisions as new practice-changing data become available.”
The panel reviewed findings from 22 new clinical trials covering androgen receptor pathway inhibitors (eg, abiraterone), PARP inhibitors, chemotherapy (eg, docetaxel), and the cell-based immunotherapy sipuleucel-T. Compared with its predecessors, the update better contextualizes for oncologists which treatment options to prioritize based on a patient’s front-line therapy.
It also incorporates knowledge from emerging areas of metastatic CRPC treatment that did not exist or were underdeveloped for prostate cancer populations in 2014. This includes the need to adopt somatic genetic testing (eg, for BRCA1/2 alterations) and the advent of radiopharmaceuticals or radioligand therapies.
“In addition to providing specific recommendations, the guideline also provides clinically meaningful information on how to improve patient-physician communication, health disparities, and the cost of medication,” Dr. Parikh added.
Given that much of this patient population is older and has multiple comorbidities and chronic conditions, the Expert Panel thought the guideline should encourage oncologists to take these and other patient factors (eg, treatment cost, quality-of-life burdens associated with treatment) into account in their decision-making.
Dr. Parikh noted that the panel also discussed the importance of incorporating palliative care, radiation oncology, and other specialists earlier in the decision-making process, because “we truly need a multidisciplinary approach to tackle this disease.”
Looking to the Future
Although the guideline update now better reflects the full range of established treatment options and approaches, other topics were too premature to include but nonetheless could prove important for treatment decision-making in the future. For example, a subset of patients may develop an aggressive variant called small cell neuroendocrine prostate cancer, which usually responds well to hormone treatment in combination with platinum-based chemotherapy, Dr. Parikh noted. However, there remains a lack of consensus about second- and third-line treatments of patients who experience disease progression on therapy. Dr. Garje added that the panel was unable to address this subpopulation further because there are no prospective trials for small cell neuroendocrine prostate cancer, and much of the existing guidance is extrapolated from small cell lung cancer.
The Expert Panel also avoided making recommendations about optimal treatment sequencing, given the variability in the eligibility criteria of the clinical trials examined.
Finally, immune-based therapies for advanced disease, such as antibody-targeted treatments (eg, monoclonal antibodies) and chimeric antigen receptor T-cell therapy, are emerging.8 However, these therapies, too, are largely absent from the guideline update, pending high-quality data about how best to use them and which patients would benefit from them.
In the meantime, the panel sought to ensure their recommendations provide clinicians with a more comprehensive, evidence-based framework that addresses common clinical scenarios encountered in daily practice. “By following these guidelines, clinicians can make more informed decisions when selecting therapies, ensuring that treatments are tailored to the unique genomic, clinical, and therapeutic context of each patient,” Dr. Garje said.
REFERENCES
1. Garje R, Riaz IB, Naqvi SAA, et al: Systemic therapy in patients with metastatic castration-resistant prostate cancer: ASCO guideline update. J Clin Oncol. May 2, 2025 (early release online).
2. Naqvi SAA, Anjum MU, Bibi A, et al: Systemic treatment options for metastatic castration resistant prostate cancer: A living systematic review. medRxiv. April 16, 2025 (early release online).
3. Elmehrath AO, Afifi AM, Al-Husseini MJ, et al: Causes of death among patients with metastatic prostate cancer in the US from 2000 to 2016. JAMA Netw Open 4:e2119568, 2021.
4. Kulasegaran T, Oliveira N: Metastatic castration-resistant prostate cancer: Advances in treatment and symptom management. Curr Treat Options Oncol 25:914-931, 2024.
5. Basch E, Loblaw DA, Oliver TK, et al: Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol 32:3436-3448, 2014.
6. Garje R, Rumble RB, Parikh RA: Systemic therapy update on 177lutetium-PSMA-617 for metastatic castration-resistant prostate cancer: ASCO rapid recommendation. J Clin Oncol 40:3664-3666, 2022.
7. Garje R, Hope TA, Rumble RB, et al: Systemic therapy update on 177lutetium-PSMA-617 for metastatic castration-resistant prostate cancer: ASCO guideline rapid recommendation Q and A. JCO Oncol Pract 19:132-135, 2023.
8. Wang I, Song L, Wang BY, et al: Prostate cancer immunotherapy: A review of recent advancements with novel treatment methods and efficacy. Am J Clin Exp Urol 10:210-233, 2022.
Originally published in ASCO Daily News © American Society of Clinical Oncology. ASCO Daily News, May 2, 2025. All rights reserved.
