SESAUA 2023: Clinical Outcomes of Patients With mHSPC With PSA Decline to Undetectable Levels on Enzalutamide: Post Hoc Analysis of ARCHES Trail

( The 2023 SESAUA annual meeting included a prostate cancer session, featuring a presentation by Dr. Russell Szmulewitz discussing a post-hoc analysis of the ARCHES trial assessing clinical outcomes of patients with metastatic hormone sensitive prostate cancer (mHSPC) with PSA decline to undetectable levels on enzalutamide.1

In the previously reported ARCHES trial (NCT02677896), enzalutamide + ADT vs placebo + ADT improved overall survival and clinical outcomes in men with mHSPC. This post hoc analysis assessed clinical endpoints in men with mHSPC who reached undetectable PSA levels on enzalutamide + ADT or placebo +ADT and investigated predictors of such a PSA decline.

Men with mHSPC were randomized 1:1 to enzalutamide (160 mg/day) + ADT or placebo +ADT, stratified by disease volume and prior docetaxel. Post hoc analyses were based on reaching undetectable (<0.2 ng/mL) or detectable (≥0.2 ng/mL) PSA levels during study treatment and included men with both detectable baseline PSA (≥0.2 ng/mL) and post-baseline PSA measurements (enzalutamide + ADT, n=507; placebo + ADT, n=504). Stepwise multivariable analysis was conducted on variables from a univariable logistic regression model to identify clinical factors that significantly correlated with PSA decline to undetectable levels.

This analysis found that PSA undetectable groups had fewer men with high-volume disease, Gleason scores ≥8, and de novo mHSPC. Of note, both enzalutamide + ADT groups had more men with these clinical factors. Men who reached undetectable PSA levels had improved clinical outcomes, including delayed radiographic progression and improved overall survival:


Key secondary endpoints from this analysis were as follows:

subgroup table.jpg

Men on enzalutamide + ADT (n=348, 68.6%) were almost four times more likely to reach undetectable PSA than men on placebo + ADT (n=89, 17.7%). Predictors of reaching undetectable PSA on enzalutamide + ADT were the absence of de novo disease (M0 vs M1: OR 4.3; 95% CI 1.8 to 10.6; p = 0.001) and baseline PSA levels (below median vs above median: OR 3.3, 95% CI 2.1 to 5.2; p < 0.0001):

multivariate table.jpg

Men who reached undetectable PSA on enzalutamide +ADT had more treatment-emergent adverse events but fewer serious and grade 3–4 treatment-emergent adverse events vs those with detectable PSA levels. Finally, safety across treatment arms was similar to prior findings.

Dr. Szmulewitz concluded his presentation discussing a post-hoc analysis of the ARCHES trial assessing clinical outcomes of patients with mHSPC with PSA decline to undetectable levels on enzalutamide with the following take-home messages:

  • Men with mHSPC in ARCHES who reached undetectable PSA levels had improved clinical outcomes and less severe adverse events
  • Men were more likely to reach undetectable PSA on enzalutamide + ADT vs placebo + ADT
  • The absence of de novo disease and baseline PSA may help identify men who reach undetectable PSA on enzalutamide + ADT

Presented by: Russell Z. Szmulewitz, MD, Department of Medicine, The University of Chicago, Chicago, IL

Co-Authors: Neal D. Shore1, Arnauld Villers2, Taro Iguchi3, Francisco Gomez-Veiga4, Antonio Alcaraz5, Arnulf Stenzl6, Boris Alekseev7, Arun A. Azad8, Daniel P. Petrylak10, Jeffrey Holzbeierlein11, Brad Rosbrook12, Fabian Zohren12, Gabriel P. Haas13, Georgia Gourgioti14, Nader N. El-Chaar13, Andrew J. Armstrong15

Affiliations: 1Department of Urology, Carolina Urologic Research Center, Myrtle Beach, SC, USA, 2Department of Urology, University Hospital Centre, Lille University, Lille, France, 3Department of Urology, Kanazawa Medical University, Ishikawa, Japan, 4Department of Urology, Salamanca University Hospital, Salamanca, Spain, 5Department of Urology, Hospital Clinic de Barcelona, Barcelona, Spain, 6Department of Urology, University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany, 7Department of Oncology, Hertzen Moscow Cancer Research Institute, Moscow, Russia, 8Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia,  10Department of Medical Oncology, Yale Cancer Center, New Haven, CT, USA, 11Department of Urologic Oncology, The University of Kansas Medical Center, Kansas City, KS, USA, 12Department of Global Biometrics and Data Management, Pfizer Inc., San Diego, CA, USA, 13Global Medical Affairs, Astellas Pharma Inc., Northbrook, IL, USA, 14Department of Biostatistics, Oncology, Astellas Pharma Inc., London, UK, 15Divisions of Medical Oncology and Urology, Cancer Institute Center for Prostate & Urologic Cancers, Durham, NC, USA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Southeastern Section of the American Urological Association (SESAUA) Annual Meeting, Amelia Island, FL, Wed, Mar 15 – Sat, Mar 18, 2023.


  1. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986.