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EMBARK: Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)

Curated by Clinicians: Educational Forum with Videos, Abstracts and Conference Information
Videos
PSA Control After Treatment Suspension: EMBARK Data at 36 Months - Neal Shore
EMBARK Trial Reports Overall Survival Benefit for Enzalutamide with ADT in High-Risk Non-Metastatic Prostate Cancer - Stephen Freedland
EMBARK Analysis: Testosterone Recovery Post-ADT in High-Risk Prostate Cancer Patients - Stephen Freedland
EMBARK Trial: Treatment Options for High-Risk Biochemical Recurrence - Neal Shore
Comparing EMBARK vs EAU High-Risk Biochemical Recurrence Criteria in Prostate Cancer - Ugo Falagario
EMBARK Trial Subanalysis for High-Risk Biochemical Recurrent Prostate Cancer - Stephen Freedland
EMBARK Trial: Age-Stratified Analysis of Enzalutamide in High-Risk Biochemically Recurrent Prostate Cancer - Neal Shore
Discussion Between Expert Clinicians and Patients on the EMBARK Trial, A Journal Club for Patients with Prostate Cancer - Matthew Cooperberg
EMBARK Trial: Enzalutamide Monotherapy & Combination Therapy for High-Risk Prostate Cancer - Stephen Freedland, Neal Shore & Rana McKay
EMBARK Trial: Enzalutamide Monotherapy and Combination Therapy for High-Risk Biochemical Recurrence - Neal Shore
The Impact of the EMBARK Trial on Treatment Decisions in High-Risk Biochemical Recurrent Prostate Cancer - Neal Shore
Advancing Prostate Cancer Care: The EMBARK Study and Implications for Clinical Practice - Stephen Freedland
Novel Hormone Therapy and Coordination of Care in High-Risk Biochemically Recurrent Prostate Cancer - Beyond the Abstract
Guideline Revisions Seek to Optimize Detection and Management of Recurrent Prostate Cancer Without Evident Metastasis, Journal Club - Rashid Sayyid & Zachary Klaassen
Parsing the Evidence from the EMBARK Trial on a Promising New Drug Regimen in High-Risk Non-Metastatic Hormone-Sensitive Prostate Cancer - Matthew Cooperberg
PSMA PET's Influence on Prostate Cancer Studies - Jeremie Calais
Interpreting EMBARK Trial Results: Intensified Treatment and Hormone Therapy in High-Risk Patients - Christian Gratzke
EMBARK Trial Shows Promising Results for High-Risk Prostate Cancer Treatment, Enzalutamide's Impact on Metastasis-Free Survival - Neal Shore
The EMBARK Study: A Phase 3 Randomized Study of Enzalutamide Plus Leuprolide and Enzalutamide Monotherapy in High-Risk Nonmetastatic Hormone-Sensitive Prostate Cancer with Rising PSA After Local Therapy - Stephen Freedland
Conference Coverage
Conference Highlights Written by Physician Scientists
Presented by Stephen J. Freedland, MD
The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting, held in Chicago, IL, hosted a poster session on Prostate, Testicular, and Penile Cancer. Dr. Stephen J. Freedland presented Abstract 5088: EMBARK: Testosterone recovery to >250 ng/dL following treatment suspension.
Presented by Neal D. Shore, MD, FACS
The 2026 American Urological Association (AUA) Annual Meeting featured a podium presentation by Dr. Neal D. Shore reporting a post hoc exploratory analysis from the phase 3 EMBARK trial evaluating the duration of treatment suspension among all randomized patients with high-risk biochemically recurrent prostate cancer.
Presented by Alessandro Viti, MD
The 2026 American Urologic Association (AUA) Annual Meeting was host to an advanced prostate cancer poster session. Dr. Alessandro Viti presented an analysis of the impact of PSMA-PET re-staging on disease classification and management for redefining EMBARK-like patients in the PSMA era.
Presented by Nadine Adriana Friedrich, MD
The American Urological Association's 2026 Annual Meeting, in Washington D.C., was host to the Interactive Poster IP38: Prostate Cancer: Advanced I Session. Dr. Nadine Adriana Friedrich presented interactive poster IP38-04: Comparison of EMBARK and EAU Criteria to Identify High-Risk Patients with Biochemical Recurrence After Radical Prostatectomy.
Presented by Fred Saad, CQ, MD, FRCS, FCAHS
The 2026 Advanced Prostate Cancer Consensus Conference (APCCC) meeting featured a management and prevention of frequent side effects and modifying the metabolism session, and a presentation by Dr. Fred Saad discussing what to expect from androgen receptor antagonist monotherapy in terms of side effects and health-related quality of life.
Presented by Derya Tilki, MD
Derya Tilki, MD, discussed the overall survival (OS) results from EMBARK, a randomized phase III trial of enzalutamide or placebo plus leuprolide acetate and enzalutamide monotherapy in high-risk biochemically recurrent prostate cancer, and the final results from PRESTO, a phase III trial of combined androgen blockade in patients with high-risk biochemically relapsed prostate cancer.
Presented by Neal Shore, MD, FACS
Neal Shore, MD, FACS, discussing a post hoc analysis of EMBARK assessing baseline features and metastasis-free survival by prior definitive treatment in patients with high‑risk biochemically recurrent prostate cancer. The phase 3 EMBARK trial showed significant improvements in metastasis-free survival with enzalutamide + leuprolide and enzalutamide monotherapy versus leuprolide alone in patients with high‑risk biochemical recurrence.
Presented by Stephen J. Freedland, MD
 The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL, was host to the Poster Session: Genitourinary Cancer - Prostate, Testicular, and Penile Cancer. Dr. Stephen J. Freedland presented Poster 5103: Secondary outcomes by prior definitive treatment (tx) in patients (pts) with high-risk biochemically recurrent prostate cancer (hrBCR) treated with enzalutamide (enza) monotherapy (mono): EMBARK post hoc analysis.
Presented by Stephen J. Freedland, MD
The AUA 2025 Annual Meeting was host to an advanced prostate cancer podium session. Dr. Stephen Freedland presented the results of an EMBARK post-hoc analysis evaluating testosterone recovery following treatment suspension of enzalutamide + leuprolide or leuprolide alone in patients with high-risk biochemically recurrent prostate cancer.
Presented by Paul R. Sieber, MD
The 2025 SESAUA annual meeting featured a prostate cancer session and a presentation by Dr. Paul Sieber discussing outcomes of men with high-risk biochemically recurrent prostate cancer who suspended enzalutamide monotherapy treatment in the phase 3 EMBARK study. Biochemical recurrence occurs in 20-50% of patients with prostate cancer within 10 years of definitive therapy, which increases the risk of prostate cancer specific mortality.
Presented by Paul R. Sieber, MD
The 2025 SESAUA annual meeting featured a prostate cancer session and a presentation by Dr. Paul Sieber discussing a post hoc analysis from the phase 3 EMBARK study assessing PSA dynamics. FDA approval of enzalutamide for treatment of non-metastatic CSPC with biochemical recurrence at high risk for metastasis, was based on data from the EMBARK trial.
Presented by Stephen J. Freedland, MD
The 2025 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Stephen Freedland discussing a post hoc analysis of EMBARK assessing secondary outcomes by prior definitive treatment in patients with high-risk biochemically recurrent prostate cancer treated with enzalutamide monotherapy. 
Presented by Neal D. Shore, MD, FACS
The 2024 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Neal Shore discussing a post hoc analysis from EMBARK focusing on age.
Presented by Stephen J. Freedland, MD
The 2024 ASCO annual meeting featured a session on prostate cancer, and a presentation by Dr. Stephen Freedland discussing a post hoc analysis of EMBARK assessing sexual activity patient-reported outcomes in patients who were sexually active or interested in sex at baseline.
Presented by Stephen J. Freedland, MD
The 2024 ASCO annual meeting featured a session on prostate cancer, and a presentation by Dr. Stephen Freedland discussing a post hoc analysis of EMBARK assessing the impact of treatment suspension on health-related quality of life.
Presented by Stephen Freedland, MD
The 2024 American Urological Association (AUA) Annual Meeting held in San Antonio, TX between May 3rd and 6th, 2024 was host to an advanced prostate cancer podium session. Dr. Stephen Freedland presented the results of a post hoc analysis of EMBARK evaluating PSA dynamics.
Presented by Bertrand Tombal, MD, PhD
The 2024 APCCC meeting featured a session on the treatment for biochemical recurrence/PSA persistence, and a presentation by Dr. Bertrand Tombal discussing patients with high-risk first biochemical recurrence after radical prostatectomy who are candidates for systemic therapy alone without local salvage radiotherapy.
Presented by Stephen Freedland, MD
(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to a prostate cancer poster session. Dr. Stephen Freedland presented an EMBARK post hoc analysis of sexual activity-related patient reported outcome measures.
Presented by Stephen Freedland, MD
(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a prostate cancer poster session. Dr. Stephen Freedland presented the results of an EMBARK post-hoc analysis evaluating enzalutamide combination treatment suspension in men with high-risk biochemically recurrent prostate cancer.
Presented by Boris A. Hadaschik, MD
(UroToday.com) At the 2023 ESMO annual meeting, Dr. Boris Hadaschik presented on prostate cancer, discussing three abstracts from the EMBARK study by Dr. Stephen Freedland, the STAMPEDE trials by Dr. Charles Parker, and fracture-related hospitalizations by Dr. Craig Jones.
Presented by Stephen J. Freedland, MD
(UroToday.com) The 2023 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Stephen Freedland discussing health-related quality of life in nonmetastatic hormone-sensitive prostate cancer patients with high-risk biochemical recurrence from the EMBARK study. Enzalutamide + leuprolide acetate and enzalutamide alone delayed metastasis-free survival (MFS) vs placebo + leuprolide acetate in high-risk BCR nonmetastatic hormone-sensitive prostate cancer in the phase 3 EMBARK trial:1
Presented by Stephen Freedland, MD
(UroToday.com) The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a prostate cancer abstracts poster session. Dr. Stephen Freedland presented results of the secondary analysis of EMBARK, specifically those pertaining to enzalutamide in combination with leuprolide acetate for the treatment of prostate cancer patients with high-risk biochemical recurrence.
Presented by Ugo F. De Giorgi, MD, PhD
(UroToday.com) The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a prostate cancer abstracts poster session. Dr. Ugo De Giorgi presented results of the secondary analysis of EMBARK, specifically those pertaining to enzalutamide monotherapy for the treatment of prostate cancer patients with high-risk biochemical recurrence.
Presented by Dr. Anne Rajkumar, MD
Dr. Rajkumar began by presenting a case of a 56-year-old male with Gleason score 4+5=9 disease, PSA 5.1 ng/ml, and with evidence of extraprostatic extension on imaging. His PSMA-PET was negative for regional and distant disease. He declined surgery in favor of radiation therapy. Given his NCCN high-risk classification, what are considerations for his hormone therapy?
Presented by Wesley R. Armstrong
(UroToday.com) The 2023 ASCO annual meeting included a prostate cancer session featuring a presentation by Wesley Armstrong discussing PSMA PET findings in an “EMBARK-like” cohort of patients with high-risk non-metastatic hormone-sensitive prostate cancer. Non-metastatic hormone-sensitive prostate cancer is defined by rising PSA levels while naïve or responsive to ADT and without evidence of metastasis on conventional imaging. 
Presented by Neal Shore, MD, FACS
(UroToday.com) Dr. Neal Shore continued the morning plenary session with an excellent presentation on the late breaking abstract regarding the EMBARK clinical trial for high risk biochemically recurrent prostate cancer. The trial started recruitment in January 2015 and accrued the final patients in August 2018.
Presented by Neal Shore, MD, FACS
(UroToday.com) The 2023 American Urological Association (AUA) annual meeting held in Chicago, IL, was host to a plenary session with Dr. Neal Shore presenting the long-awaited results of EMBARK, a phase 3 randomized study of enzalutamide or placebo plus leuprolide acetate and enzalutamide monotherapy in high-risk biochemically recurrent prostate cancer.
Publications
Peer-Reviewed Journal Abstracts

In the phase 3 EMBARK trial, enzalutamide plus leuprolide and enzalutamide monotherapy were associated with longer metastasis-free survival than leuprolide alone among patients with biochemically recurrent prostate cancer.

The game-changing EMBARK trial1 extended the indication for intensified systemic treatment to biochemical-only recurrent prostate cancer with high-risk features, such as an absolute PSA level ≥ 1ng/ml (after initial radical prostatectomy) and a PSA doubling time of less than 9 months. However, this trial relied on conventional imaging, and many of these patients would have had positive PSMA-PET findings.2

Serum tumor markers can be a blessing and a curse. After definitive local therapy for prostate cancer, prostate-specific antigen (PSA) is quite sensitive and specific, and can detect micrometastatic disease well before any radiographic or symptomatic evidence of disease. When biochemical recurrence (BCR) occurs, early detection can guide curative-intent salvage therapies such as salvage radiation.

Purpose/Objective(s): The primary analysis of EMBARK demonstrated that after a median follow-up of 60.7 months metastasis-free survival (MFS) for enzalutamide (enza) + leuprolide acetate (LA; hazard ratio [HR] 0.42; 95% confidence interval [CI], 0.30–0.61; p<0.0001) and enza monotherapy (mono; HR 0.63; 95% CI, 0.46–0.87; p=0.0049) was clinically meaningful and statistically superior to placebo + LA. Here, we present a subgroup analysis of MFS by prior radiotherapy (RT).
Biochemical recurrence (BCR) has been defined as rising prostate-specific antigen (PSA) levels after definitive therapy (e.g., radical prostatectomy or radiotherapy) without evidence of metastasis by conventional imaging (i.e., bone scan and computed tomography).1

Enzalutamide and Quality of Life in Prostate CancerFreedland et al. present the health-related quality of life outcomes for patients with biochemically recurrent prostate cancer who were randomly assigned to enzalutamide plus leuprolide, enzalutamide monotherapy, or leuprolide alone (EMBARK trial).

XTANDI becomes the first and only androgen receptor signaling inhibitor approved for use with or without a GnRH analog therapy* in nonmetastatic castration-sensitive prostate cancer

Reno, Nevada (UroToday.com) -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) and Pfizer Inc. (NYSE: PFE) announced that the companies received an approval by the U.S. Food and Drug Administration (FDA) of a supplemental New Drug Application for XTANDI® (enzalutamide),
If approved, XTANDI would become the first and only novel hormone therapy approved in this earlier type of prostate cancer


Reno, Nevada (UroToday.com) --Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for the companies' supplemental New Drug Application (sNDA) for XTANDI® (enzalutamide)

Volume 209, Supplement 4, Page e1190: The abstract text is as given below. This erratum also includes the additional disclosure, conflict of interest, and acknowledgments that were not included in the original publication.

  • Data from Phase 3 EMBARK trial to be presented as a plenary session during the 2023 American Urological Association Annual Meeting
  • Results show the potential for XTANDI to add to the standard of care in prostate cancer, if approved
Reno, Nevada (UroToday.com) -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) and Pfizer Inc. (NYSE: PFE) announced that XTANDI® (enzalutamide) plus leuprolide significantly reduced the risk of metastasis or death by 58%
Pfizer and Astellas announce positive topline results from Phase 3 EMBARK trial

Reno, Nevada (UroToday.com) -- Pfizer Inc. and Astellas Pharma Inc. announced positive topline results from the Phase 3 EMBARK trial evaluating XTANDI® (enzalutamide) in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR).

Limited data from controlled clinical trials are available for men who experience biochemical recurrence after definitive therapy for prostate cancer. In the absence of overt metastases, patients with non-metastatic castration-sensitive prostate cancer (nmCSPC) often receive androgen deprivation therapy (ADT).