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Contemporary Management of nmCRPC

Curated by clinicians: educational forums with videos, abstracts and conference information
Zachary Klaassen, MD, MSc

Zachary Klaassen, MD, MSc

Dr. Klaassen is a Urologic Oncologist, Associate Professor of Urology, Residency Program Director and the Ronald W. Lewis, MD Endowed Chair for Urologic Education at Wellstar MCG Health; Georgia Cancer Center in Augusta, GA. He was born in rural Canada and grew up in Vancouver, British Columbia. Following an undergraduate degree in Molecular Biology and Biochemistry at Simon Fraser University, he attended medical school at St. George's University in Grenada, followed by clinical rotations and a research fellowship in the metro New York area. After completing his Urology residency in Augusta, he spent two years in Toronto as a Society of Urologic Oncology fellow, obtaining a Masters of Science degree from the University of Toronto in Clinical Epidemiology. He specializes in Urology, Urologic Oncology, Robotic Surgery, Minimally Invasive Surgery, and Cancer Surgery. Dr. Klaassen is interested in treating patients with urologic malignancies, including prostate, bladder, kidney, testis, and penile cancer, using both open and minimally invasive surgical techniques. His research interests include mental health and cancer survivorship, clinical epidemiology of urologic malignancies, clinical trials, and translational research on biomarkers for early cancer detection and treatment response predictors. He believes in taking the cancer journey together with his patients and their families, focusing on treating not only the cancer but also the physical and emotional side effects of diagnosis and treatment.

Videos
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Clinical Conversations by Experts
Theranostics in nmCRPC: From PSMA PET Imaging to Lutetium-177 Therapy - Sherief Gamie
ARAMIS Trial: PSA Responses with Darolutamide Linked to Minimal Radiographic Progression - Alicia Morgans
Navigating Non-Metastatic Castration-Resistant Prostate Cancer Treatment in the PSMA PET Era - Neal Shore
Non-Metastatic Castration-Resistant Prostate Cancer in the Era of PSMA PET Imaging - Aaron Berger
The Impact of Advanced Imaging on Detection and Treatment in Nonmetastatic CRPC - Vahan Kassabian
Navigating the Nuances: Exploring Imaging Options and Impact to Treatment Strategies in nmCRPC - Ryan Malone
Trends in Prostate Cancer Diagnosis in Transgender Women - Farnoosh Nik-Ahd
223Ra Use Before 177Lu-PSMA for Patients with Bone-predominant mCRPC, The RAdium LUtetium (RALU) Study, Journal Club - Zachary Klaassen
Depression, Bone Health and Exercise in Prostate Cancer - Fred Saad, Tomasz Beer & Charles Ryan
Mental Health and Impact on Patients with GU Malignancies - Zachary Klaassen
Time Course Profile of Adverse Events With Darolutamide in the ARAMIS Trial – Christian Gratzke
Delayed Deterioration in Patient Quality of Life, the Impact of Darolutamide on Local Symptoms in the ARAMIS Trial – Neal Shore
STAMPEDE Analysis of Abiraterone With or Without Enzalutamide Added to Androgen Deprivation Therapy Compared to ADT Alone In High-Risk Non-Metastatic Prostate Cancer Patients– Gerhardt Attard
Biological Signatures of Patients with Long-Term Responses to Apalutamide and Placebo in Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)- Felix Feng
Overall Survival Data from the Global, Phase 3 ARAMIS Trial in Men with Non Metastatic Castration-Resistant Prostate Cancer (nmCRPC) - Karim Fizazi
Pembrolizumab in mCRPC Patients with Microsatellite Instability High (MSI-H) Detected by Circulating Tumor DNA - Pedro Barata
Predictors of Survival, Healthcare Resource Utilization, and Healthcare Costs in Veterans with Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC) - Stephen Freedland
Significantly Longer Metastasis-Free Survival and Overall Survival in the ARAMIS Trial, Nonmetastatic Castration-Resistant Prostate Cancer - Christopher Wallis & Zachary Klaassen
Final Overall Survival Analysis of the PROSPER Trial in Nonmetastatic Castration-Resistant Prostate Cancer - Karim Fizazi
ARAMIS Trial Demonstrates Significant Improvement in Overall Survival in nmCRPC - Neal Shore
Overall Survival Results of Phase III ARAMIS Study of Darolutamide Added to ADT for Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) - Karim Fizazi
ARAMIS Trial: Darolutamide Demonstrates Improved Overall Survival in Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) - Fred Saad
Treatment Advances in Non-Metastatic Castration-Resistant Prostate Cancer - Evan Yu
Prolonging Overall Survival in Men with Non-metastatic Castration Resistant Prostate Cancer ARAMIS Trial - Neal Shore
Optimal Treatment of Newly Diagnosed Metastatic Prostate Cancer Presentation - Noel Clarke
The Definition and Overview of Treatment Options in nmCRPC Presentation - Howard Scher
The Treatment of Non-Metastatic Castration-Resistant Prostate Cancer: "Pros" Presentation - Maha Hussain
The "Cons" of Treating nmCRPC - Important Considerations to Take into Account Presentation - Celestia Higano
Darolutamide Treated Patients Maintained Quality of Life in ARAMIS Trial - Fred Saad
Benefits of Early AR Targeting in Metastatic Hormone Sensitive Disease and nmCRPC - Karim Fizazi
Darolutamide Demonstrates Efficacy and Safety in Men with nmCRPC - Neeraj Agarwal
ARAMIS - Efficacy and Safety of Darolutamide in nmCRPC - Karim Fizazi
Racial Disparities in Prostate Cancer Treatment and Outcomes - Susan Halabi
Abiraterone Acetate for nmCRPC, The Forgotten Dance Partner? - Zach Klaassen and Chris Wallis
Comparison Between Surgery and Radiotherapy in the Treatment of Non-Metastatic Prostate Cancer- Christopher Wallis
Phase III ARAMIS Trial Darolutamide in Patients with Non-metastatic Castration-resistant Prostate Cancer Meets Primary Endpoint - Tom Keane
nmCRPC Patient Population - Discussion with Charles Ryan and Alicia Morgans
The PROSPER Trial: Chemotherapy-Related Endpoints in Patients with nmCRPC - Neal Shore
Updates on Health-Related Quality-of-Life (HRQoL) analyses in GU Oncology - Cora Sternberg
AUA Castration-Resistant Prostate Cancer Guidelines - Interview with Michael Cookson
The Incredible Shrinking nmCRPC - Phillip Koo
nmCRPC Outcomes in the Use of New Androgen Receptor Targeted Therapies - A Conversation with Charles Ryan and Alicia Morgans
nmCRPC - Early Treatment Leading to Favorable Outcomes - Fred Saad.
Meeting an Unmet Need in the Nonmetastatic Castration Resistant Prostate Cancer Patient Population - Maha Hussain
Physician-Scientist Review Articles
State of the Evidence Review Articles
Written by Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
December 13, 2022
External beam radiotherapy, along with radical prostatectomy, has been a mainstay treatment option for prostate cancer for decades and is currently recommended by numerous guidelines for the treatment of intermediate- and high-risk disease.1-3 While it is clear that radiotherapy should include the tumor, the prostate, and seminal vesicles, the role of prophylactic pelvic nodal irradiation for patients without overt evidence of regional pelvic nodal involvement has long been debated. 
Written by Zachary Klaassen, MD, MSc
September 17, 2020
While there have been dramatic changes in treatment options for patients with advanced prostate cancer over the past 5 years, perhaps the greatest change has been for patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Prior to February 14, 2018, there were no agents approved by the United States Food and Drug Administration (FDA) for men with nmCRPC.
Written by Zachary Klaassen, MD, MSc
April 16, 2019
Over the last two or more years, the treatment of men with M0 CRPC has drastically changed, most recently with the approval of darolutamide in this disease space based on data from the ARAMIS trial. The objective of this article is to provide a contemporary review of treatment options for men with non-metastatic CRPC.
Physician-Scientist Commentaries
Peer-reviewed Abstract Supplemental Commentaries
Written by Stephen J. Freedland, MD
In castration-resistant prostate cancer (CRPC), tumor progression occurs despite low, castrate levels of serum testosterone.1 Non-metastatic CRPC (nmCRPC) is characterized by the absence of detectable metastases and prostate-specific antigen (PSA) levels that continue to rise even though patients continue to receive androgen-deprivation therapy.2 Patients with nmCRPC are at risk of progression to metastatic disease and nmCRPC patients with shorter PSA doubling time (PSADT) have increased risk of metastasis and poorer clinical outcomes.3–5
Written by Neal Shore, MD, FACS
The FDA’s approval of the second-generation androgen receptor inhibitors (SGARIs)—apalutamide, enzalutamide, and darolutamide—in 2018‒2019 expanded therapeutic options for patients with non-metastatic castration resistance prostate cancer (nmCRPC)
Written by Jeanny B. Aragon-Ching, M.D., F.A.C.P.
Darolutamide is a novel anti-androgen that is recently approved for men with non-metastatic castration-resistant prostate cancer. Darolutamide is structurally different from the previously discovered androgen receptor (AR) agents enzalutamide, bicalutamide and apalutamide.
Conference Coverage
Conference Highlights Written by Physician Scientists
Presented by Murilo de Almeida Luz, MD
The 2026 American Urological Association (AUA) Annual Meeting featured a poster presentation by Dr. Murilo de Almeida Luz and colleagues reporting post hoc analyses from the international DAROL study evaluating the safety, effectiveness, and health-related quality of life (HRQoL) of darolutamide in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) stratified by comorbidity burden.
Presented by Ursula Vogl, MD
The 2026 EAU annual meeting featured a plenary prostate cancer session and a presentation by Dr. Ursula Vogl discussing the optimal management of oligorecurrent disease, and that systemic therapy should be used for oligorecurrent lesions. Dr. Vogl’s discussion was based on a prior case presentation of a 61-year-old fit man with oligo-recurrent prostate cancer after radical prostatectomy, 
Presented by Murilo De Almeida Luz, MD
The 2026 ASCO GU Annual Symposium was host to a prostate cancer poster session. Dr. Murilo De Almeida Luz presented a post-hoc analysis of DAROL evaluating the real-world safety and efficacy of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC) patients by lipid-modifying agent use.
Presented by Martin Boegemann, MD
The 2025 ESMO annual meeting featured a prostate cancer session and a presentation by Martin Boegemann, MD, discussing estimation of median overall survival to inform the ESMO-MCBS scores in non-metastatic castration-resistant prostate cancer (nmCRPC) using the ARAMIS study.
Presented by Christopher Pieczonka, MD
The 2025 AUA annual meeting featured an advanced prostate cancer session and a presentation by Dr. Christopher Pieczonka discussing data from the prespecified third interim analysis of the darolutamide observational (DAROL) study in North American patients with non metastatic castration resistant prostate cancer (nmCRPC). Darolutamide is a highly potent androgen receptor inhibitor that is structurally distinct by design, with low blood-brain barrier penetration and limited potential for drug-drug interactions.
Presented by Daniel George, MD
The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA was host to a prostate cancer poster session. Dr. Daniel George presented the results of a real-world analysis assessing the use and outcomes of darolutamide (DARO), enzalutamide (ENZA), and apalutamide (APA) for nonmetastatic castration-resistant prostate cancer (nmCRPC), stratified by race subgroup.
Presented by Megan Crumbaker, MBBS (Hons), PhD, FRACP
The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to the Trials in Progress Poster Session A: Prostate Cancer. Dr. Megan Crumbaker presented the trial in progress poster 298: Bipolar androgen therapy (BAT) for nonmetastatic castration-resistant prostate cancer (nmCRPC) progressing on darolutamide: Working Out M0 BAT (WOMBAT; ANZUP 2201).
Presented by Alicia K. Morgans, MD, MPH
 The 2024 ASCO Annual Meeting held in Chicago, IL was host to a prostate, testicular, and penile cancers poster session. Dr. Alicia Morgans presented the results of a follow-up analysis of ARAMIS evaluating the association between PSA level <0.2 ng/ml and risk of radiological progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).
Presented by Alicia Morgans, MD, MPH
The 2023 ESMO annual meeting included a trial in progress session on prostate cancer, featuring a presentation by Dr. Alicia Morgans discussing ARASTEP, a phase 3, randomized, double-blind, placebo-controlled study assessing darolutamide + ADT in patients with high-risk biochemical recurrence of prostate cancer.
Presented by Alicia Morgans, MD, MPH
The 2023 ASCO annual meeting included a prostate cancer session featuring a presentation by Dr. Alicia Morgans discussing DEAR, a comparative real-world evidence study of darolutamide, enzalutamide, and apalutamide for patients with nmCRPC in the United States. Novel androgen receptor inhibitors (ARIs) are recommended for patients with nmCRPC.
Presented by Neal Shore, MD, FACS
At the 2023 AUA annual meeting Dr. Neal Shore presented the results of DEAR, a real-world study on darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC) patients using a United States-based urology network.
Presented by Evan Yu, MD

At the 2022 ASCO Annual Meeting, the poster session focused on Prostate, Testicular, and Penile cancers included a presentation from Dr. Evan Yu examining real-world outcomes for patients treated with darolutamide in advanced prostate cancer.

 

Presented by Amanda E. Hird, MD,
In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Hird presented results of a population-based analysis of the prevalence and natural history of non-metastatic castration-resistant prostate cancer (nmCRPC).
Presented by Pierre Blanchard, MD
The 2022 APCCC Hybrid Meeting included a session on the management of non-metastatic castrate-resistant prostate cancer (nmCRPC), and a presentation by Dr. Pierre Blanchard discussing treatment of the primary or local relapse in this disease space.
Presented by Karim Fizazi, MD, PhD
Darolutamide (DARO) is a structurally distinct androgen receptor inhibitor (ARI) that has been demonstrated to significantly prolong metastasis-free survival and overall survival in the ARAMIS trial.1
Presented by Susan Feyerabend
Darolutamide significantly prolonged metastasis-free survival (MFS) and overall survival (OS) vs placebo (PBO) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in ARAMIS.
Presented by Karim Fizazi, MD, PhD
Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) need therapy that prolongs survival with little added toxicity, thus preserving quality of life.
Presented by Neal D. Shore, MD, FAC
In plenary abstract presentation in the Poster Highlights Session: Prostate Cancer - Localized Disease session at the 2021 ASCO GU meeting, Dr. Shore and colleagues presented an analysis examining the effect of crossover on the overall survival benefit seen in ARAMIS.
Presented by Maha H. A. Hussain, MD, FACP, FASCO
To provide guidance on expected outcomes and explore the influence of PSA dynamics further, in a plenary abstract presentation in the Poster Highlights Session: Prostate Cancer session at the 2021 ASCO GU Cancers Symposium, Dr. Hussain and colleagues presented an analysis of overall survival and metastasis-free survival among patients in the PROSPER trial according to the depth of PSA response.
Presented by Matthew R. Smith, MD, Ph.D
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in nmCRPC
Presented by Alicia Morgans, MD, MPH 
In a stand-alone session at this year’s Society of Urologic Oncology (SUO) virtual annual meeting, titled Understanding the Evolving Treatment Landscape in Prostate Cancer: How to Leverage the Latest Advances and Strategies to Optimize Patient Outcomes,
Presented by Karim Fizazi, MD, Ph.D.
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer, at GU ASCO in February 2018, there were no specifically approved treatment options for these patients.
Presented by Karim Fizazi, MD, PhD
There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer, at GU ASCO in February 2018, there were no specifically approved treatment options for these patients.
Presented by Karim Fizazi, MD, Ph.D.
Darolutamide is a unique androgen receptor inhibitor, FDA approved in July 2019 for the treatment of non-metastatic castration-resistant prostate cancer. This approval was based on ARAMIS,1 a large multicenter double-blind, placebo-controlled study that randomized 1500 patients to 600 milligrams of darolutamide twice a day or placebo.
Presented by Boris Hadaschik, MD
Athens, Greece (UroToday.com) Dr. Boris Hadaschik presented on the disease entity of non-metastatic castrate-resistant prostate cancer (nmCRPC).
Presented by Matthew R. Smith, MD, PhD
Barcelona, Spain (UroToday.com) The randomized, phase 3 SPARTAN trial showed that apalutamide offered a metastasis-free survival (MFS) benefit over placebo for patients with non-metastatic
Presented by Christopher Parker, MD
Barcelona, Spain (UroToday.com) The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. Supporters of adjuvant radiotherapy suggest that earlier treatment may be more effective,
Presented by Matthew R. Smith, MD, PhD
Barcelona, Spain (UroToday.com) In the phase III placebo-controlled SPARTAN study, apalutamide with ongoing androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS) (HR 0.28, 95% CI, 0.23-0.35),
Presented by Teuvo Tammela, MD, PhD
Barcelona, Spain (UroToday.com)  Dr. Teuvo Tammela presented results of the recently published ARAMIS trial. Non-metastatic (M0) CRPC (nmCRPC) is defined as a rising PSA in the setting of non-metastatic disease in the castrate state.
Presented by Karim Fizazi, MD, PhD
San Francisco, CA (UroToday.com) The use of androgen-axis targeted agents, specifically enzalutamide and abiraterone, have drastically changed the landscape of advanced prostate cancer management. Just last year, at GU ASCO 2018,
Presented by Neil Fleshner, MD, MPH, FRCSC
Toronto, Ontario (UroToday.com) Dr. Neil Fleshner presented the question in debate of whether we should be treating non-metastatic castrate-resistant prostate cancer (nmCRPC) patients or wait until they have developed metastases.
Presented by Maha Hussain, MD, FACP, FASCO
San Francisco, CA (UroToday.com) Dr. Maha Hussain provided the first presentation of the phase III randomized double-blind controlled trial, the following men were eligible for inclusion
Publications
Articles and Abstracts

Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide.

The EAU guidelines and the latest recommendations from the US Prostate Cancer Conference suggest a castration threshold of 20 ng/dl. However, the current NCCN and AUA guidelines still recommend a castration standard of 50 ng/dl.

The recent evidences provided in metastatic hormone sensitive prostate cancer (nmHSPC) and in nonmetastatic castration resistant (nmCRPC) introduced the possibility to adopt Androgen Receptor Signaling inhibitor (ARSi) alone (both settings) or with chemotherapy (in mHSPC).