What is the probability of prostate cancer recurrence if restarting Testosterone Replacement Therapy (TRT)?

Probability of Prostate Cancer Recurrence When Restarting TRT

The probability of prostate cancer recurrence when restarting testosterone replacement therapy (TRT) cannot be precisely quantified due to inadequate evidence, but limited data suggest that carefully selected patients with favorable pathology after definitive treatment may restart TRT with relatively low risk of recurrence.1

Patient Selection for TRT After Prostate Cancer Treatment

Post-Radical Prostatectomy Patients

• TRT can be considered in men with:
  • Favorable pathology (negative margins, negative seminal vesicles, negative lymph nodes)
  • Undetectable PSA postoperatively
  • Limited data shows no significant increases in prostate cancer recurrence in these patients1
  • Caution: PSA increases have been observed in high-risk groups receiving testosterone

Post-Radiation Therapy Patients

• Available studies suggest patients treated with RT (with or without prior androgen deprivation therapy) generally:
  • Do not experience recurrence or progression of prostate cancer
  • Show either steady decline in PSA values to <0.1 ng/mL or non-significant PSA changes1

Active Surveillance Patients

• Limited data available
• Patients with and without high-grade prostatic intraepithelial neoplasias on TRT did not show:
  • Significant increases in PSA
  • Subsequent cancer diagnosis compared to men not receiving testosterone1

Monitoring Protocol for TRT After Prostate Cancer

PSA Monitoring

• PSA levels should be monitored on the same schedule as men without testosterone deficiency
• Consider increasing frequency of testing1
• PSA recurrence should be evaluated in the same fashion as untreated men
• Be prepared to stop TRT if concerning PSA changes occur

Risk Stratification

• Higher risk of recurrence in patients with:
  • High-risk pathology (Gleason score ≥8)
  • Positive surgical margins
  • Extracapsular extension
  • Seminal vesicle invasion
  • Lymph node involvement

Evidence Quality and Limitations

• Current studies are underpowered and of too short duration to detect long-term effects1
• Most research involves retrospective analyses with small sample sizes2, 3
• The AUA guidelines note "inadequate evidence to quantify the risk-benefit ratio of testosterone therapy" in men with history of prostate cancer1
• Longer follow-up periods and larger prospective studies are needed

Clinical Approach to Decision-Making

1. Assess patient's prostate cancer risk profile:

   • Low/favorable risk: Consider TRT with close monitoring
   • High risk: Avoid TRT or use extreme caution

2. Evaluate time since definitive treatment:

   • Longer disease-free interval suggests lower recurrence risk

3. Consider severity of hypogonadal symptoms:

   • Balance quality of life benefits against potential cancer risks

4. Implement vigilant monitoring:

   • Regular PSA testing
   • Digital rectal examination
   • Prompt investigation of concerning changes

Important Caveats

• The decision to commence TRT in men with history of prostate cancer should be made with caution1
• Patients must be informed that there is inadequate evidence to quantify the risk-benefit ratio1
• TRT in men with locally advanced or metastatic disease remains poorly understood and should ideally be performed under research settings1
• Case reports exist of synchronous metastatic prostate cancer and male breast cancer following TRT4

Conclusion

While limited evidence suggests TRT may be reasonably safe in carefully selected patients after definitive prostate cancer treatment, the exact probability of recurrence cannot be precisely quantified. The decision requires careful risk assessment, thorough patient counseling, and vigilant monitoring.