2026-09-22

Prostate

Prior RT and ADT were excluded, so these results don't carry over to hypogonadism after RT or salvage RT.

Early signal

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.

Why it mattersRadiation oncology

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.

Monday clinic

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. The longer read

10 details 1 trial watching

Design

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.

Population & inclusion

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.

Regimen

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%.

Endpoints

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.

Safety

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.

vs leading data

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.

Applies to

hypogonadal men with low-grade pT2 disease and durably undetectable PSA after RP

Does not represent men treated with RT or ADT, or those with high-grade disease.

Limitations

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.

Discussion

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.

Results

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

Enrolment

CONSORT flow

Randomized136

↓

Testosterone cypionate

allocated 68

Placebo

allocated 68

Rationale

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.

Open questions

Long-term oncologic safety of TRT after RP

recruiting Impact of Peri-operative tEstosterone Levels on oNcological and Functional Outcomes in RadiCal prostatEctomy Phase 3

n=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

Sourced from Bhasin et al.

📚 Sources · 📄 1 paper

📄 PAPER Bhasin; Burnett; Gagliano-Jucá et al. · JAMA internal medicine (2026-07)

Testosterone Treatment in Prostate Cancer Survivors With Hypogonadism: A Randomized Clinical Trial.

PMID 42113507 → doi full text (PMC)

Abstract

IMPORTANCE: A majority of men with prostate cancer have low-grade cancer and an excellent prognosis after radical prostatectomy. Hypogonadism and associated symptoms impair quality of life in prostate cancer survivors. Many guidelines, citing a lack of randomized clinical trials showing safety and efficacy of testosterone replacement therapy (TRT), consider a history of prostate cancer a contraindication for TRT. OBJECTIVE: To evaluate the short-term safety and efficacy of TRT in prostate cancer survivors with symptomatic hypogonadism. DESIGN, SETTING, AND PARTICIPANTS: This randomized, placebo-controlled, double-blind, parallel-group, phase 2 trial was conducted at 2 academic medical centers in men 40 years and older with organ-confined, low-grade prostate cancer (Gleason score of 6 [3 + 3] or 7 [3 + 4]). Participants had undetectable prostate-specific antigen (PSA) for at least 2 years after radical prostatectomy, a mean of 2 testosterone levels less than 275 ng/dL, and low libido, erectile dysfunction, or fatigue. Patients were allocated using concealed, block randomization, with stratification for age (40-60 years or >60 years) and phosphodiesterase-5 inhibitor (PDE5I) use. The first participant was randomized on May 13, 2019, and the last study visit was completed on May 16, 2025. INTERVENTION: Testosterone cypionate, 100 mg, or placebo intramuscularly weekly for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was sexual activity. Secondary outcomes included sexual desire, erectile function, well-being, body composition, aerobic capacity, and physical function. The safety outcome was biochemical recurrence (PSA ≥ 0.2 ng/mL). RESULTS: A total of 136 men were randomized, 68 to receive testosterone cypionate, 100 mg, and 68 to receive placebo, and 125 men completed the study. Groups were similar at baseline (mean [SD] age, 68.6 [6.5] years; 52 [38%] had a Gleason score of 6; and 84 [62%] had a Gleason score of 7). No participant in either group experienced biochemical recurrence. TRT significantly increased sexual activity more than placebo, adjusted for PDE5I use and age (between-group difference, 0.91 daily events [95% CI, 0.56-1.26]; P < .001). TRT increased sexual desire and prostate cancer quality-of-life sexual domain score, and decreased negative affect more than placebo. Erectile function did not change. TRT significantly improved body composition, loaded stair-climbing power, and peak aerobic performance (VO2 peak) compared with placebo. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, TRT for 12 weeks in men treated with radical prostatectomy for low-grade prostate cancer significantly improved sexual activity, sexual desire, well-being, body composition, physical function, and aerobic performance compared to placebo without biochemical recurrence. The trial was neither long enough nor large enough to evaluate clinical recurrence or long-term safety; this proof-of-concept trial was essential for rationalizing a larger, long-term study. These findings do not apply to men with high-grade prostate cancer or those treated with androgen deprivation therapy or radiation therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03716739.

Systemic Supportive Phase 2 trial Early signal

🌰 Prostate

Testosterone Treatment in Prostate Cancer Survivors (Bhasin RCT) NCT03716739

Prostate