Testosterone Replacement After Prostatectomy for Prostate Cancer
Testosterone replacement therapy can be considered in elderly men after radical prostatectomy for prostate cancer, but only in carefully selected patients with favorable pathology (negative margins, negative seminal vesicles, negative lymph nodes) and undetectable PSA postoperatively. 1
Patient Selection Criteria
The decision to initiate testosterone therapy requires strict adherence to specific pathological and biochemical criteria:
- Favorable surgical pathology is mandatory: negative surgical margins, negative seminal vesicles, and negative lymph nodes 1
- Undetectable PSA postoperatively must be documented and maintained 1
- Low to intermediate risk disease (Gleason score ≤7 with 3+4 pattern, stage pT2, N0, M0) represents the safest population for consideration 2, 3
- Avoid in high-risk or locally advanced disease: men with high-risk features should ideally only receive testosterone under research protocols 1
Evidence Quality and Limitations
The 2018 AUA Guideline explicitly acknowledges that currently available studies are underpowered and of too short duration to detect any effects attributable to testosterone therapy 1. This represents a critical caveat—while limited data show no significant increases in prostate cancer recurrence compared to controls, the evidence base remains insufficient to quantify the true risk-benefit ratio 1, 3.
Recent research supports relative safety in select populations. A 2016 study of 82 hypogonadal men with prostate cancer treated with testosterone (including 22 post-prostatectomy patients) found no biochemical recurrence in the radical prostatectomy group over median 41-month follow-up 4. A 2013 retrospective review of 103 men post-prostatectomy showed only 4 recurrences with testosterone therapy versus 8 in untreated controls, though PSA did increase significantly 3.
Informed Consent Requirements
Patients must be explicitly informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy after prostate cancer treatment 1. The AUA states this as Expert Opinion, reflecting the uncertainty in this clinical scenario. Key discussion points include:
- No evidence links testosterone therapy to the development of prostate cancer in the general population 1
- Theoretical concern exists that testosterone may accelerate growth of occult residual cancer cells 1
- PSA will likely increase during therapy, which may complicate surveillance but does not necessarily indicate recurrence 4, 3
- Long-term safety data beyond 36 months are lacking 1, 3
Monitoring Protocol
Rigorous PSA surveillance is non-negotiable when initiating testosterone therapy in this population:
- Baseline PSA must be undetectable (ideally <0.01 ng/mL) before starting therapy 1
- Monitor PSA on the same schedule as men without testosterone deficiency, though clinicians may increase testing frequency 1
- Consider more aggressive biopsy thresholds: PSA increase >1.0 ng/mL in the first 6 months or >0.4 ng/mL per year thereafter warrants urologic evaluation 1
- For PSA increases of 0.7-0.9 ng/mL, repeat testing in 3-6 months and perform biopsy if further elevation occurs 1
- Monitor hematocrit: testosterone therapy can cause erythrocytosis, with intervention warranted at hematocrit >54% 1, 5
Contraindications
Absolute contraindications per FDA labeling include known or suspected prostate cancer 5. However, the AUA guideline creates nuance for this population by stating therapy "can be considered" post-prostatectomy with favorable features 1. This apparent contradiction reflects evolving understanding but mandates extreme caution.
Do not initiate testosterone in men with:
- Metastatic or locally advanced disease (should only occur in research settings) 1
- Detectable PSA after prostatectomy 1
- High-risk pathology (positive margins, seminal vesicle invasion, lymph node involvement) 1
- Biochemical recurrence 1
Clinical Pitfalls to Avoid
The most common error is failing to appreciate that PSA increases during testosterone therapy do not automatically indicate cancer recurrence 4, 3. PSA velocity in treated patients averages 0.001-0.12 μg/L per year in post-prostatectomy patients on testosterone, which differs from untreated recurrence patterns 4.
Do not confuse the saturation model of androgen sensitivity with blanket safety: while prostate cancer may become androgen-indifferent at higher testosterone concentrations, this does not eliminate risk in men with residual microscopic disease 6. The theoretical framework supporting testosterone safety remains incompletely validated in clinical practice.
Avoid testosterone therapy as routine practice: the AUA recommends proceeding "with caution" (Moderate Recommendation, Evidence Level Grade C), reflecting genuine uncertainty about long-term oncologic outcomes 1.
Quality of Life Considerations
Testosterone deficiency significantly impairs quality of life in prostate cancer survivors, affecting sexual function, energy, muscle mass, and cognitive performance 2, 7. The potential benefits of testosterone replacement—improved erectile function, libido, energy, and body composition—must be weighed against uncertain oncologic risks 7, 3. This represents a genuine clinical dilemma where patient values and preferences should guide decision-making after thorough informed consent 1.