EORTC GUCG 2238: “Deescalate,” a pragmatic trial to revisit intermittent androgen deprivation therapy in metastatic hormone-sensitive prostate cancer in the era of new androgen receptor pathway inhibitors.

TPS5150 Background: The systemic standard of care treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC) according to international guidelines is combination therapies with androgen deprivation therapy (ADT) + androgen receptor pathway inhibitor (ARPI) +/- docetaxel. These ADT + ARPI combinations (also called maximum androgen blockade, MAB) 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 (HRQoL). Treatment usually continues until biochemical, radiological, or clinical progression, sometimes many years after treatment initiation, exposing patients to chronic side effects affecting their HRQoL. 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 (OS). In this study, we hypothesized that patients with mHSPC treated with MAB reaching PSA ≤ 0.2 ng/ml may benefit from treatment interruption without compromising OS. Methods: The primary goal of this academic-led, open-label, pragmatic, randomized phase III study is to investigate whether intermittent MAB (iMAB) 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 MAB (cMAB). Co-primary endpoints are: 1) Feasibility: proportion of patients who do not restart their MAB within one year of interruption. 2) Efficacy: OS assuming the iMAB regimen at three years is non-inferior to continuous treatment. Secondary objectives include toxicity, HRQoL and assessing the impact on treatment resources between iMAB and cMAB. The study will randomize 1600 patients to exclude a 4% OS difference at 3 years while <30% of patients restarted MAB after one year. The study is currently active in Belgium, Croatia, Denmark, Ireland, France and Spain. The activation of the other countries (Portugal, Italy, Romania, Slovenia, Switzerland and Czech Republic) is expected by spring 2026. The study has currently recruited 109 patients (Updated January 26, 2026). Clinical trial information: NCT05974774 .