How to manage a patient on TRT with fluctuating PSA levels and a negative prostate MRI?

Management of PSA Fluctuations in a Patient on TRT with Negative Prostate MRI

For a 51-year-old man on testosterone replacement therapy (TRT) with fluctuating PSA levels (3.6,1.8,2.2, and 2.4) and a negative prostate MRI, continued TRT is appropriate with close PSA monitoring every 3-6 months.

Assessment of Current Clinical Picture

The patient presents with:

• 51 years of age
• On testosterone replacement therapy (TRT)
• PSA values showing fluctuation: 3.6,1.8,2.2, and 2.4 ng/mL
• Negative prostate MRI

Interpretation of PSA Values

• The fluctuating PSA values do not show a consistent rising pattern
• The most recent values (2.2.4) show relative stability
• All values remain below the traditional threshold of 4.0 ng/mL
• The initial value of 3.6 ng/mL followed by lower values suggests a possible temporary elevation rather than progressive disease

Management Recommendations

Continue Monitoring with Regular PSA Testing

• Continue PSA monitoring every 3-6 months while on TRT 1
• Ensure consistent laboratory testing (same assay and laboratory) to minimize variability 2
• Schedule testing at approximately the same time of day to reduce circadian variations 2

PSA Velocity Calculation and Monitoring

• Calculate PSA velocity using at least 3 measurements over a minimum of 3 months 2
• Be alert for:
  • PSA velocity >0.4 ng/mL per year while on TRT 1
  • Any increase of >1.0 ng/mL during the first six months of treatment 1

Testosterone Level Monitoring

• Monitor testosterone levels concurrently with PSA 2
• Ensure testosterone levels remain relatively stable (ideally ≤10% variation) 2
• Maintain testosterone levels within physiologic range (typically 350-1000 ng/dL)

Indications for Urological Referral

Refer to urology if any of the following occur:

• PSA increases to >4.0 ng/mL
• PSA velocity exceeds 0.75 ng/mL per year 1
• Any single PSA increase of >1.0 ng/mL 1
• Development of abnormal findings on digital rectal examination

Interpretation of Negative MRI

• A negative prostate MRI is reassuring but does not completely rule out prostate cancer
• MRI has high soft tissue contrast and characterization but may miss small lesions 2
• The negative MRI in this case supports continued monitoring rather than immediate biopsy

Special Considerations for TRT

• TRT can cause modest PSA elevations in hypogonadal men (average increase of 0.47 ng/mL over 12 months) 3
• Approximately 5% of men on TRT may experience PSA increases ≥1.7 ng/mL 3
• PSA levels are inappropriately low in hypogonadal men and may increase with normalization of testosterone 4

Algorithm for Future Management

1. Continue TRT with current regimen

2. Monitor PSA every 3-6 months

3. If PSA remains stable or fluctuates without consistent rise:

   • Continue current management
   • Consider extending PSA monitoring to every 6 months after 1 year of stability

4. If PSA shows concerning changes:

   • PSA >4.0 ng/mL
   • PSA velocity >0.75 ng/mL/year
   • Single increase >1.0 ng/mL
   • Then:
     • Temporarily hold TRT
     • Refer to urology for evaluation
     • Consider repeat prostate MRI and possible biopsy

5. After urological clearance (if needed):

   • Resume TRT at potentially lower dose
   • Return to more frequent PSA monitoring (every 3 months)

Pitfalls and Caveats

• Laboratory variability in PSA testing can be 20-25%; confirm significant elevations with repeat testing 1
• Avoid PSA testing within 48 hours of ejaculation or vigorous physical activity 1
• PSA fluctuations may occur without indicating cancer progression
• A single PSA measurement should not be relied upon for clinical decisions 1
• TRT should be temporarily discontinued if significant PSA elevation occurs until urological clearance 1