(UroToday.com) The 2026 ASCO annual meeting featured a prostate cancer trials in progress session and a presentation by Dr. Fabio Turco discussing EORTC GUCG 2238 DE-ESCALATE, a pragmatic trial to revisit intermittent ADT in metastatic hormone-sensitive prostate cancer (mHSPC) in the era of new androgen receptor pathway inhibitors (ARPIs). The systemic standard of care treatment in patients with mHSPC according to international guidelines is combination therapies with ADT + ARPI +/- docetaxel.
These ADT + ARPI combinations (also called maximum androgen blockade) have been shown in phase 3 randomized clinical trials to reduce the risk of death by 20-40%, delay further treatment, and improve health-related quality of life. Treatment usually continues until biochemical, radiological, or clinical progression, sometimes many years after treatment initiation, exposing patients to chronic side effects affecting their health-related quality of life.
Registration trials included highly selected patients, not representative of the general population, thereby overestimating treatment adherence and effectiveness while underreporting tolerability. Several sub-analyses of the registration trials demonstrated that patients achieving a PSA ≤0.2 ng/ml have prolonged overall survival. In this study presented at ASCO 2026, Dr. Turco and colleagues hypothesized that patients with mHSPC treated with maximum androgen blockade reaching PSA ≤ 0.2 ng/ml 6-12 months may benefit from treatment interruption without compromising overall survival.
The primary goal of this academic-led, open-label, pragmatic, randomized phase III study is to investigate whether intermittent maximum androgen blockade can be safely administered to mHSPC patients who reached a PSA ≤ 0.2 ng/mL at 6 to 12 months after the start of treatment (docetaxel and radiotherapy permitted as part of standard treatment), as compared to continuing maximum androgen blockade. The trial design for DE-ESCALATE is as follows:
The co-primary endpoints are: (i) feasibility, defined as the proportion of patients who do not restart their maximum androgen blockade within one year of interruption, and (ii) efficacy, defined as overall survival assuming the intermittent maximum androgen blockade regimen at three years is non-inferior to continuous treatment. The secondary objectives include toxicity, health-related quality of life, and assessing the impact on treatment resources between intermittent maximum androgen blockade and continuing maximum androgen blockade.
The study will randomize 1,600 patients to exclude a 4% overall survival difference at 3 years, while <30% of patients restarted maximum androgen blockade after one year. The study is currently active in Belgium, Croatia, Denmark, Ireland, France, Spain, and Switzerland. The activation of the other countries (Italy, Romania, Slovenia, and the Czech Republic) is expected soon. As of May 1, 2026, the trial has recruited 211 patients.
Presented by: Fabio Turco, MD, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026