What are the next steps for a 67-year-old man on Testosterone Replacement Therapy (TRT) for hypogonadism with a family history of prostate cancer and rising Prostate-Specific Antigen (PSA) levels from 2.0 to 3.18 to 3.89?

Management of Rising PSA in a 67-Year-Old Man on TRT with Family History of Prostate Cancer

This patient should be referred for a prostate biopsy based on his rising PSA levels while on testosterone replacement therapy (TRT) and family history of prostate cancer.

Assessment of Current Situation

• The patient's PSA has risen from 2.0 to 3.89, showing a concerning upward trend while on TRT 1
• The patient has two significant risk factors:
  • Age (67 years old) 2
  • Family history of prostate cancer (brother) 1
• While his current PSA is below the traditional 4.0 ng/ml threshold, the pattern of increase is concerning 1

Recommended Management Algorithm

Immediate Actions

• Refer for prostate biopsy based on:
  • PSA increase of approximately 1.89 ng/ml over the monitoring period 1
  • This exceeds the threshold of 1.0 ng/ml increase that warrants biopsy according to multiple guidelines 1
  • Family history increases his baseline risk 1

Monitoring and Follow-up

• If biopsy is negative:

  • Continue TRT with close monitoring 3
  • Perform PSA testing every 3-6 months 1
  • Conduct digital rectal examination at each follow-up 1
  • Consider repeat biopsy if PSA continues to rise by more than 0.4 ng/ml/year 1

• If biopsy reveals prostate cancer:

  • Discontinue TRT immediately 4
  • Proceed with appropriate prostate cancer treatment based on stage and grade 2

Evidence-Based Rationale

The New England Journal of Medicine guidelines specifically recommend prostate biopsy for men on TRT who experience:

• A yearly PSA increase of 1.0 ng/ml or more 1
• PSA increases of 0.7-0.9 ng/ml warrant repeat PSA measurement in 3-6 months and biopsy if any further increase occurs 1

This patient's PSA has increased by 1.89 ng/ml, which exceeds these thresholds and justifies immediate biopsy 1.

Important Considerations

• While TRT itself does not appear to cause prostate cancer, it may unmask previously occult cancer 1, 3
• Men with family history of prostate cancer should have a lower threshold for biopsy while on TRT 1, 2
• PSA levels are typically lower in hypogonadal men and may increase with TRT even without cancer, but increases of this magnitude warrant investigation 5
• The mean numerical increase in PSA with TRT is typically only 0.30-0.43 ng/ml; this patient's increase is substantially higher 1, 3

Pitfalls to Avoid

• Don't dismiss rising PSA as merely due to TRT - While TRT can cause modest PSA increases, this patient's rise exceeds typical expectations 1
• Don't delay biopsy based on PSA still being under 4.0 ng/ml - The rate of change is more concerning than the absolute value 1
• Don't discontinue TRT before biopsy - This may mask cancer; diagnosis should be made while on current therapy 1, 5
• Don't ignore family history - Brother with prostate cancer significantly increases this patient's risk 1, 2