In men with high-risk BCR (PSADT ≤ 9 months) after definitive local therapy, the phase III EMBARK trial randomized patients 1:1:1 to enzalutamide plus leuprolide, enzalutamide monotherapy, or leuprolide plus placebo within a protocol incorporating planned intermittent therapy (“drug holiday”). In these high-risk patients, enzalutamide plus leuprolide or enzalutamide alone may be offered after radical prostatectomy with a PSA ≥ 1.0 ng/mL or PSA ≥ 2.0 ng/mL above nadir after radiotherapy.  In the EMBARK study, eligibility was based on conventional imaging.Treatment could be suspended if PSA declined below a prespecified nadir threshold (e.g., <0.2 ng/mL at week 36), with reinitiation triggered by protocol-defined PSA rises. The primary endpoint, metastasis-free survival (MFS), was significantly improved with enzalutamide plus leuprolide versus leuprolide alone (5-year MFS approximately 87.3% versus 71.4%; HR ~0.42), and enzalutamide monotherapy also improved MFS (HR ~0.63). Updated results demonstrated a significant OS benefit for the combination arm versus ADT alone (approximately 78.9% versus 69.5% 8-year OS; HR ~0.60), confirming durable benefit with early intensified androgen receptor inhibition within a PSA nadir-guided intermittent framework. The PRESTO (AFT-19) trial71enrolled men with high-risk BCR after prostatectomy and adjuvant or salvage radiotherapy and a short PSADT (≤9 months), randomizing patients to a finite 52-week course of ADT alone, ADT plus apalutamide, or ADT plus apalutamide plus abiraterone/prednisone, followed by structured observation. This design intentionally incorporated treatment cessation after completion of therapy, with PSA nadir and subsequent PSA rises defining progression endpoints. Both intensified regimens significantly prolonged PSA-PFS compared with ADT alone (median PSA-PFS approximately 24.9–26.0 months versus 20.0–20.3 months; HRs ~0.48–0.52), without significant delays in testosterone recovery. Mature metastasis-free and OS outcomes are pending, but these data support finite intensified androgen blockade guided by PSA kinetics in high-risk BCR. In addition, data from historical studies using ADT monotherapy further support the role of intermittent therapy. One RCT demonstrated the safety of an intermittent approach. An open-label trial by Crook et al. (n=1,386) compared intermittent versus continuous ADT in patients with a PSA rise to >3ng/mL more than 1 year following primary or salvage radiotherapy for localized prostate cancer.72 An important limitation of this study to note is the lack of any stratifying criteria or initial risk factors. Intermittent therapy consisted of an eight-month treatment cycle. At the end of the 8-month cycle, treatment was discontinued if there was no evidence of clinical disease progression, the PSA level was <4ng/mL and did not increase more than 1ng/mL. It is further noted that the PSA threshold to reinitiate the next cycle of ADT was a level of 10ng/mL. At a median follow-up of 6.9 years, there was no difference in survival between intermittent versus continuous ADT (median 8.8 versus 9.1 years, (HR=1.02; 95% CI: 0.86 to 1.21), meeting the predefined non-inferiority threshold. There was also no difference in prostate cancer-specific survival (HR=1.18; 95% CI: 0.90 to 1.55). Intermittent therapy was associated with better scores for hot flashes (p<0.001), desire for sexual activity (p<0.001), and urinary symptoms (p=0.006) compared with continuous therapy. Another open-label EC507 trial (n=109) study compared intermittent versus continuous ADT in patients with a PSA increase to ≥1ng/mL following an initial decrease to <0.5ng/mL within 3 months of radical prostatectomy.73 All patients underwent induction with leuprorelin acetate, and patients who achieved a PSA level <0.5ng/mL during induction were randomized to intermittent versus continuous ADT. In the intermittent therapy arm, ADT was resumed if PSA levels increased to ≥3ng/mL. The primary outcome of the trial was testosterone recovery, which was achieved in 79.3% of patients in the first intermittent ADT cycle and 64.9% during the second intermittent ADT cycle. There was no difference between intermittent versus continuous ADT in time to castration resistance (mean 976 versus 986 days, p=0.85); OS and PFS were not reported.