Prostate
Testosterone recovery post-ADT discontinuation (podcast review)
TL;DRReview of two datasets: 25% of real-world pts recovered T within 12mo; 54% relugolix vs 3% leuprolide at 90d in HERO.
HERO
For short-course ADT with RT, the recovery question is now quantified: only 25% of real-world pts on injectable ADT had documented T >280 ng/dl within 12mo of stopping, and testing happened in only about 40% at all. The authors position relugolix for short-term or intermittent regimens, not continuous long-term ADT.
In men finishing a defined course of ADT, especially short-term ADT with RT or an intermittent strategy, these data support checking testosterone after discontinuation rather than assuming recovery; they do not inform men on continuous long-term ADT.
Short-course ADT with definitive or salvage RT is exactly the setting the authors name as where recovery matters, and the real-world number is sobering: 25% recovery to >280 ng/dl within 12mo, in a cohort where only about 40% were tested at all. That argues for scheduling a post-ADT testosterone check rather than assuming recovery.
The choice between an oral GnRH antagonist and a depot agonist carries a recovery consequence in this post hoc read: 54% vs 3% at 90 days, median 86 vs 112 days. Relevant when planning intermittent or defined-duration ADT, not continuous therapy.
10 details 4 trials watching
Sponsored podcast article (Pfizer with Sumitomo Pharma), reviewing two published papers: a retrospective real-world Optum EHR/oncology cohort (2020-2021 data) and a post hoc subgroup of the phase 3 HERO trial. No new analysis is presented here.
Real-world cohort: 3875 men who initiated and discontinued injectable ADT, of whom 1553 (about 40%) had at least one testosterone test within 12 months of stopping. HERO subgroup: 184 men who completed 48 weeks of ADT, 137 relugolix and 47 leuprolide.
Relugolix 360 mg loading dose then 120 mg orally once daily; leuprolide IM every 12 weeks. The real-world cohort predates relugolix availability, so it covers injectable formulations only.
Recovery thresholds differ between the two sources. Real-world: testosterone >280 ng/dl on any test within 12 months. HERO subgroup: >280 ng/dl or >80% of baseline, assessed to 90 days post discontinuation.
Real-world recovery was 25% (390/1553) at 12 months, with lower adjusted risk of new-onset diabetes (HR 0.47, 0.27-0.79). HERO 90-day cumulative incidence was 54% relugolix vs 3% leuprolide (nominal p=.002), median time to recovery 86 vs 112 days.
| Outcome | HR | 95% CI |
|---|---|---|
| New-onset diabetes | 0.47 | 0.27-0.79 |
| New-onset depression | 0.58 | 0.33-1.02 |
| Treatment for sexual dysfunction | 1.33 | 0.99-1.78 |
| Subgroup | Relugolix | Leuprolide |
|---|---|---|
| Overall cumulative incidence | 54% | 3% |
| Baseline T at/above pretreatment median | 71% | 6% |
| Age ≤65 | 78% | 13% |
| Age >65 | 47% | 0% |
| Biochemical recurrence | 57% | 0% |
In the HERO post-discontinuation window, any AE and grade 3+ AE were 96% and 15% in both groups over 30 days; serious AEs 12% relugolix vs 11% leuprolide. Day-90 PSA rose slightly more with relugolix (0.39 vs 0.06 ng/ml), with no correlation between rising testosterone and rising PSA.
The two sources are not comparable on their own terms: different recovery definitions, different windows (12 months vs 90 days), and no relugolix in the real-world arm, so the cross-source read is descriptive only. The 86 vs 112 day medians come from a window that ends at 90 days, so the leuprolide median sits beyond the observation period.
The clinically usable claim is the testing-behaviour one: recovery is rarely documented because testosterone is rarely measured after ADT stops. Whether faster biochemical recovery translates into the bone, metabolic and mood outcomes cited as the motivation is untested here.
- Does faster testosterone recovery improve bone, metabolic or cardiovascular outcomes n=110 · primary completion 2027-07 · relugolix vs leuprolide: cholesterol, glucose, QoLrecruiting REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial Phase 3n=72 · primary completion 2029-07 · phase 3 cardiac endpoints, relugolix vs leuprolide + AA
- Recovery rates beyond 90 days with relugolix not yet Relugolix in Combination With Radiation Therapy for Treating Patients With High Risk Prostate Cancer Phase 2n=90 · primary completion 2025-10 · relugolix duration comparison with DXA + RT
- Recovery after longer ADT durations than 48 weeks active Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED) Phase 2n=33 · primary completion 2028-11 · T recovery rate after 2y relugolix + darolutamide