Testosterone Treatment in Prostate Cancer Survivors (Bhasin RCT) NCT03716739
ForHypogonadal men post-RP, pT2 Gleason 3+3/3+4, undetectable PSA ≥2 yr
TL;DRSexual activity +0.91 daily events vs placebo (95% CI 0.56-1.26, P<.001), zero biochemical recurrences, 12wk TRT in hypogonadal men post-RP for Gleason 3+3/3+4.
Men treated with RT or ADT were excluded, so the zero-BCR signal does not transfer to post-RT survivors, the hypogonadal population a radiation oncologist actually follows. Post-RT pts retain prostate tissue, and this trial offers no data on TRT against that background.
In hypogonadal men with undetectable PSA ≥2 years after RP for pT2 Gleason 3+3 or 3+4 disease, this supports short-term TRT as an evidence-backed option for sexual symptoms; it does not extend to post-RT, post-ADT, or higher-grade survivors.
For the urologist following hypogonadal men after RP for pT2 Gleason 3+3/3+4 disease, this provides the first randomized efficacy data for TRT, with an effect above the stated MCID. It does not settle oncologic safety: 0 vs 0 BCR over 12 wk plus 3 mo in a near-zero-risk cohort cannot rule out harm.
10 details 1 trial watching
Randomized, placebo-controlled, double-blind, parallel-group phase 2 (SPIRIT), 2 academic centers, 1:1, N=136. Enrollment May 2019 to last visit May 2025; target revised from 142 to 134 with DSMB concurrence.
Men ≥40 post-RP for organ-confined pT2N0M0, Gleason 3+3 or 3+4, preop PSA <10, undetectable PSA ≥2 yr. Hypogonadal (T <275 ng/dL and/or free T ≤70 pg/mL) plus low libido, ED, or fatigue. Mean age 68.6; 38% Gleason 6, 62% Gleason 7.
Testosterone cypionate 100 mg IM weekly × 12 wk vs placebo. Total T rose 349 ng/dL (95% CI 283-415) more than placebo; adherence 95% vs 94%.
Primary efficacy: change in sexual activity (PDQ question 4). Primary safety: biochemical recurrence (≥2 consecutive PSA ≥0.2 ng/mL). Secondary: desire, erectile function, affect, body composition, VO2 peak, stair-climb power.
No biochemical recurrence in either arm. Erythrocytosis in 3 TRT pts; SAEs 1 vs 3; no MACE or VTE. One TRT pt had detectable PSA 0.1 to <0.2 ng/mL during treatment.
Described by the authors as the first randomized placebo-controlled trial of TRT in prostate cancer survivors; prior support for TRT after RP rested on observational series. Many guidelines still list prostate cancer history as a TRT contraindication.
Baseline recurrence risk in this cohort is so low that 0 vs 0 BCR carries little information about harm. Erectile function did not move despite EPIC-26 gains, and no P value adjustment was made across secondaries.
The efficacy case for TRT in this population is now randomized and exceeds the MCID. The safety case remains a short-horizon absence of events, which justifies a larger long-term trial rather than settling the contraindication.
| Endpoint | Treatment effect (95% CI) | P |
|---|---|---|
| Sexual activity (PDQ-4), 1° EP | 0.91 (0.56 to 1.26) | <.001 |
| Sexual desire (DISF-SD) | 2.96 (1.46 to 4.45) | <.001 |
| EPIC-26 sexual domain | 5.35 (1.63 to 9.07) | .005 |
| Erectile function (IIEF) | 0.93 (−0.43 to 2.29) | .18 |
| Energy | 1.43 (−0.53 to 3.40) | .15 |
| PANAS positive affect | 0.60 (−0.85 to 2.04) | .42 |
| PANAS negative affect | −1.39 (−2.53 to −0.25) | .02 |
| Event | Placebo | Testosterone |
|---|---|---|
| Biochemical recurrence | 0 | 0 |
| ≥1 AE, pts (events) | 47 (138) | 49 (160) |
| SAEs, pts (events) | 1 (1) | 3 (3) |
| Erythrocytosis (Hb >18 g/dL) | 0 | 3 (3) |
| MACE | 0 | 0 |
| VTE | 0 | 0 |
| Bone fractures | 3 (3) | 0 |
CONSORT flow
Efficacy primary met in a clean double-blind RCT, but the question that gates practice (oncologic safety) is untestable at N=136 and 12 wk; authors frame it as proof-of-concept.
- Long-term oncologic safety of TRT after RP recruiting Impact of Peri-operative tEstosterone Levels on oNcological and Functional Outcomes in RadiCal prostatEctomy Phase 3n=140 · primary completion 2027-12 · phase 3 TRT gel vs placebo post-RP, oncologic outcomes
- TRT safety in post-RT or higher-grade survivors
- Durability of benefit beyond 12 weeks
📚 Sources · 📄 1 paper
Abstract
The longer read
The trial answers the question it could answer and is candid about the one it could not. On efficacy, the result is clean: a double-blind, placebo-controlled design with concealed randomization, an adjusted between-group difference in sexual activity of 0.91 daily events against a prespecified minimal clinically important difference of 0.5, and consistent movement in desire, the EPIC-26 sexual domain, negative affect, and lean mass. None of that is surprising; testosterone does these things in hypogonadal men generally. What is new is that it has now been shown under randomization in men with a prostate cancer history, which removes one argument guidelines have leaned on, namely that no randomized evidence exists.
The safety readout needs a more careful reading. Zero biochemical recurrences in both arms sounds reassuring, but the eligibility criteria selected men whose baseline recurrence risk over a six-month window was already close to nil: pT2N0M0, Gleason 3+3 or 3+4, preoperative PSA under 10, and PSA undetectable for at least two years. In that population one would expect no events whether testosterone promotes regrowth or not. The absence of recurrence here is compatible with safety but cannot discriminate it from modest harm. The PSA kinetics are marginally more informative: one TRT participant drifted to the 0.1 to under 0.2 ng/mL band, which is the kind of signal a longer trial would need to track, not dismiss.
The erectile function null is worth noting. EPIC-26 sexual domain improved while IIEF erectile function did not differ between arms, which fits a post-prostatectomy population in which erections are limited by nerve and vascular injury rather than androgen deficiency. Testosterone appears to act on desire and activity, not on the mechanical deficit, and clinicians should set expectations accordingly.
Blinding deserves some skepticism. Testosterone produces perceptible physiologic effects, and erythrocytosis occurred only in the treated arm; participants may have inferred allocation, and every sexual and affective outcome here is patient-reported. Secondary endpoints were not adjusted for multiplicity. Neither concern threatens the primary result much given its magnitude and the objective lean mass changes, but they temper confidence in the softer secondaries.
For radiation oncologists the boundary is the finding. Men treated with RT or ADT were excluded, so the trial says nothing about the irradiated prostate, where residual glandular tissue, benign PSA production, and bounce complicate surveillance on androgen replacement. Extrapolating the zero-recurrence result to post-RT survivors would import reassurance from a population with no prostate and near-zero risk into one with both. The same limit applies to higher-grade disease. What the trial does establish is a design template and an effect size that make a larger, longer safety trial feasible, which the authors state was its purpose.