TRT in Prostate Cancer Survivors (Bhasin RCT) NCT03716739
ForLow-grade (GG1-2) PCa post-RP, PSA undetectable ≥2y, symptomatic hypogonadism
0.91 daily events
95% CI 0.56-1.26, P<.001
TL;DRSexual activity +0.91 daily events vs placebo (95% CI 0.56-1.26, P<.001) with 12wk testosterone; zero biochemical recurrences in low-grade post-RP hypogonadal men.
RT-treated men were excluded by design, and the authors state the findings do not apply to them; this trial gives no safety data for TRT after definitive RT or ADT. For the post-RT survivor asking about testosterone, the evidence gap is unchanged, and the zero-BCR result in undetectable-PSA post-RP men does not transfer.
In a Gleason 3+3 or 3+4 post-prostatectomy man with PSA undetectable for ≥2 years and symptomatic low testosterone, this supports discussing short-term TRT; it does not extend to high-grade disease or men treated with RT or ADT.
Randomized, blinded data now counter the blanket contraindication for low-grade post-RP survivors, with zero BCR over 12 weeks. That window cannot assess slower androgen-driven recurrence, and the authors exclude ADT-treated and high-grade disease, so any survivorship TRT discussion stays limited to that narrow group.
The enrolled population is the urologic post-prostatectomy follow-up clinic: Gleason ≤3+4, organ-confined, PSA undetectable ≥2y. Libido, energy and body composition improved over 12 weeks, but erectile function did not, so post-RP erectile complaints still need their own pathway.
9 details
Randomized, placebo-controlled, double-blind phase 2 at 2 academic centers; concealed block randomization stratified by age (40-60 vs >60y) and PDE5I use. Enrollment May 2019 to last visit May 2025.
Men ≥40y with organ-confined Gleason 6 or 7 (3+4) PCa, undetectable PSA ≥2y after RP, mean testosterone <275 ng/dL, plus low libido, ED, or fatigue. Mean age 68.6; 38% Gleason 6, 62% Gleason 7.
Testosterone cypionate 100 mg IM weekly for 12 weeks vs placebo.
Primary: sexual activity. Secondary: sexual desire, erectile function, well-being, body composition, aerobic capacity, physical function. Safety: biochemical recurrence (PSA ≥0.2 ng/mL).
Sexual activity rose by 0.91 daily events (95% CI 0.56-1.26, P<.001). Desire, QoL sexual domain, negative affect, body composition, stair-climb power and VO2 peak improved; erectile function did not change.
No biochemical recurrence in either arm over 12 weeks; 125 of 136 completed.
Guidelines treat prior PCa as a TRT contraindication, citing absence of randomized safety and efficacy data; this is randomized, blinded evidence in that population, though only for short-term exposure.
Erectile function, often the complaint driving the TRT request, did not move. Single dose and 2 academic sites; generalizability to other formulations and community practice untested.
Efficacy is established for the short term; the open question is oncologic safety, which zero BCR events in 12 weeks cannot settle. The authors position this as the rationale for a larger long-term trial.
CONSORT flow
Clean randomized double-blind design hits efficacy EP, but 12wk exposure and N=136 leave the oncologic safety question (BCR) unpowered; authors call it proof-of-concept.
- Long-term clinical recurrence risk with prolonged TRT
- Safety of TRT after definitive RT or ADT
- Applicability to high-grade prostate cancer survivors
📚 Sources · 📄 1 paper
Abstract
The longer read
The contribution here is not the efficacy signal, which few would have doubted, but that the question was tested at all in a randomized, blinded frame. Guideline positions labelling prior prostate cancer a contraindication to testosterone rest, by the source's own account, on the absence of randomized data rather than on randomized evidence of harm. This trial removes the first half of that justification for a narrow population and leaves the second half, long-term oncologic safety, essentially where it was.
The population selection is doing most of the work on safety. Enrolled men had organ-confined Gleason 6 or 3+4 disease, radical prostatectomy, and PSA undetectable for at least two years. That is a group whose baseline recurrence risk over any 12-week window is very low, so the absence of biochemical recurrence in either arm is the expected result under the null as well as under the hypothesis that testosterone is safe. With 68 men per arm and three months of exposure, the trial could only detect a large, fast-acting stimulatory effect on residual disease. Its failure to see one is reassuring against that specific scenario and silent on the slower biology that actually concerns clinicians: late recurrence years after exposure to eugonadal androgen levels.
On efficacy, the design is clean. Concealed randomization, double blinding, stratification for PDE5 inhibitor use and age, and a prespecified primary endpoint give the 0.91 daily-event difference (95% CI 0.56-1.26) real credibility. The pattern of secondaries is coherent with androgen physiology: desire, mood, body composition and aerobic performance improved, while erectile function did not. That last finding matters in clinic, because post-prostatectomy sexual complaints are frequently erectile and neurovascular in origin, and TRT will not address them. Counselling should separate libido and energy, where this trial shows benefit, from erections, where it does not.
The boundary conditions the authors draw are unusually explicit and should be respected. Men treated with radiation or ADT were excluded, as was high-grade disease. For a radiation oncologist this means the trial offers nothing for the post-RT survivor, where the prostate remains in situ, PSA is not expected to be undetectable, and biochemical recurrence definitions differ. Extrapolating the zero-event result into that setting would be a population error, not a reasonable inference.
What would make the result misleading is a delayed effect: androgen exposure that does not raise PSA within 12 weeks but shortens time to recurrence over years. Only the larger, longer trial the authors call for can address that. Until then, this is permission to discuss short-term TRT with a carefully selected post-prostatectomy man, framed as symptom benefit with an unresolved long-term risk.