Phase 2 ADT + ARPI androgen-receptor signaling inhibition with risk-adapted de-escalation in mHSPC

Georgetown University and the MedStar Health network are running this prospective, interventional, non-randomized Phase 2 pragmatic study (up to 108 patients) to test whether a risk-adapted intensification strategy followed by planned treatment de-escalation can preserve disease control while reducing long-term hormonal side effects in metastatic hormone-sensitive prostate cancer. Core systemic therapy uses androgen deprivation therapy (ADT; suppresses gonadal androgen production) plus an androgen receptor pathway inhibitor (ARPI; blocks androgen receptor signaling), with high-risk patients also receiving docetaxel (a microtubule/tubulin inhibitor chemotherapy) unless contraindicated. Local therapy (prostate radiation and, in some patients, brachytherapy and/or radiation to metastatic sites) is incorporated, then patients who sustain deep PSA response (≤0.2 ng/mL at 36 months) can elect surveillance off ARPI with protocol-defined restart triggers. The key scientific/commercial angle is pragmatic “real-world” de-intensification (intermittent-style therapy) in an era where many patients receive lifelong ADT + ARPI ± docetaxel; today’s care for mHSPC is continuous ADT combined with an ARPI (often plus docetaxel in fit, higher-risk patients) with radiation sometimes used for select low-volume disease, and this study asks whether some responders can safely stop therapy to improve quality-of-life and sexual function.