Is a detectable PSA level and altered testosterone level normal in a patient with a history of Gleason 9 prostate cancer treated with ADT, HDR brachytherapy, and IMRT?

PSA and Testosterone Levels Post-Treatment for Gleason 9 Prostate Cancer

Yes, a detectable PSA and suppressed testosterone are expected findings in your clinical scenario—patients treated with radiation therapy (RT) rarely achieve undetectable PSA due to residual benign prostatic tissue, and testosterone recovery after ADT cessation is frequently incomplete or delayed. 1

Understanding Your PSA Status

Why Detectable PSA is Normal After Radiation

• Patients treated with RT (including HDR brachytherapy and IMRT) are unlikely to have undetectable PSA due to residual prostatic tissue, unlike surgical patients who typically achieve undetectable levels. 1 This represents benign prostate tissue, malignant tissue, or a combination of both.

• The key metric is not whether PSA is detectable, but rather:

  • What is your PSA nadir (lowest value achieved)? This becomes your baseline reference point. 1
  • Is PSA rising above nadir + 2 ng/mL? The Phoenix definition (ASTRO 2006) defines biochemical failure as a rise of 2 ng/mL or more above the nadir PSA. 1
  • What is your PSA doubling time (PSADT)? This requires at least 3 PSA values over 3 months with minimum 4-week intervals between measurements. 1

Critical Monitoring Requirements

• All PSA values must be obtained using the same assay at the same laboratory to avoid variability from different testing methods. 1

• Testosterone concentration should be relatively stable (ideally ≤10% variation) when calculating PSADT, as PSA levels are directly influenced by testosterone levels. 1 PSADT should not be calculated when testosterone is rebounding post-ADT. 1

• For post-brachytherapy patients specifically, several factors can transiently elevate individual PSA measurements: physical or sexual activity, prostatitis, radiation proctopathy, recent kidney stone passage, or instrumentation. PSA bounces from infection or inflammation can take 6-8 weeks to resolve. 1

Understanding Your Testosterone Status

Expected Testosterone Recovery Patterns

• After 6 months of GnRH agonist therapy, testosterone does not return to normal for a median of 16.6 weeks. 1 This is the expected recovery timeline for short-term ADT.

• For patients who received long-term ADT (2-3 years as recommended for Gleason 9 disease), testosterone recovery is significantly impaired. 1 Recent data shows that at 5 years after ADT cessation, only 50% of men who received long-term LHRH agonist/antagonist therapy recovered to mean baseline testosterone levels, and most failed to recover to eugonadal levels. 2

• Suppressed testosterone levels are therefore expected and common in your situation, particularly given the high-risk nature of Gleason 9 disease requiring long-term ADT (2-3 years). 1

Clinical Implications of Persistent Testosterone Suppression

• Testosterone deficiency is associated with metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and hypogonadal symptoms. 2 Your testosterone levels should be monitored regularly even after ADT cessation.

• If testosterone remains in the castrate range, this may actually be therapeutically beneficial for cancer control, though it comes with quality-of-life trade-offs. 1

What You Should Monitor Going Forward

PSA Surveillance Protocol

• Obtain PSA measurements at 4-week intervals over at least 3 months to establish a reliable trend before making clinical decisions. 1

• Calculate PSADT only after obtaining at least 3-4 values over 3+ months, ensuring testosterone levels are stable during this period. 3

• If PSA rises 2 ng/mL above your nadir, this constitutes biochemical failure and warrants restaging with PSMA PET/CT if available (for PSA >0.2 ng/mL). 1

Testosterone Monitoring

• Check testosterone levels concurrently with PSA measurements to ensure stability when interpreting PSA trends. 1

• A testosterone measurement within the castrate range at any point during continuous ADT therapy should suffice for documentation, though measurement at diagnosis and at first recurrence may be clinically useful. 1

Common Pitfalls to Avoid

• Do not compare PSA values from different laboratories or assays, as they are not interchangeable and introduce significant variability. 3

• Do not obtain PSA within 2 weeks of ejaculation, prostate manipulation, or vigorous physical activity, as these can transiently elevate PSA. 3

• Do not calculate PSADT during testosterone rebound periods post-ADT, as this will yield inaccurate results. 1

• For radiation-treated patients, consider nadir subtraction when calculating PSADT to normalize values comparable to surgical patients, though this is not universally required. 1