CUA: Testosterone Suppression (2018)

See Original Guideline

Benefit of low testosterone during androgen-deprivation therapy (ADT)

• See Hormonal Therapy Chapter Notes
• ADT is the standard first-line treatment for men with recurrent or metastatic prostate cancer.
• Studies have consistently demonstrated the clinical benefit and importance of greater testosterone suppression during ADT.
  • The largest trial (PR-7) enrolled 626 patients with localized or locally advanced prostate cancer treated with ADT (orchiectomy, or luteinizing hormone-releasing hormone (LHRH) agonist (LHRHa) therapy plus a non-steroidal anti-androgen for at least 4 weeks) and found that time to CRPC and OS were significantly improved in patients with a serum testosterone ≤0.7 nmol/l.
• Achieving a serum testosterone level of ≤0.7 nmol/l is associated with improved survival and is the target level of supression

Frequency of testosterone and PSA testing

• Consider monitoring testosterone every 3–6 months, or as appropriate, during the first year to ensure target levels are achieved
  • Once the target threshold has been reached, lengthening the monitoring frequency as appropriate for a patient’s risk of relapse would be acceptable.
• Regular monitoring of PSA level is also recommended every 3–6 months, or as clinically appropriate.

Accuracy of testing and collaboration with clinical labs

• Immunoassay may not be sufficiently specific, sensitive, accurate, or reproducible in the detection of castrate level serum testosterone unless the method is externally validated against mass spectrometry
• Validated liquid chromatography-mass spectrometry/mass spectrometry methods are the gold standard for castrate level testosterone assays, with adequate specificity, sensitivity, and accuracy at low concentrations (≤0.7 nmol/l)

Management

• Testosterone levels during ADT reflect the efficacy of treatment, while the serum PSA concentrations are a reflection of disease control. Preferably, both testosterone and PSA levels remain low (≤0.7 nmol/l and ≤2 ng/ml, respectively), but if either begins to rise, reassessment and a change in therapeutic strategy may be warranted. There are two general scenarios defined by testosterone level (i.e., inadequate vs. adequate testosterone suppression) that can be used to guide treatment strategy, with further differentiation according to relative PSA levels.
• Inadequately suppressed testosterone
  • See Figure 2 from Original Guideline
  • For those with stable PSA (non-metastatic or metastatic), a testosterone level above 0.7 nmol/l may indicate treatment failure and alternate medical or surgical treatments should be considered
  • For those with rising PSA, inadequate testosterone suppression may also indicate treatment failure. For non-metastatic or metastatic disease, alternate medical or surgical treatments should be considered.
  • In either case, combined androgen blockade with a non-steroidal anti-androgen may provide protection against the effects of failure to suppress serum testosterone below 0.7 nmol/l; however, for those with metastatic disease, testosterone level <1.7 nmol/l and PSA >2 ng/ml, treatment for CRPC should be implemented.

• Adequately suppressed testosterone
  • See Figure 3 from Original Guideline
  • Rising PSA in the context of suppressed testosterone may indicate CRPC.
  • For non-metastatic patients, addition or withdrawal of an anti-androgen may be considered, while treatment for the management of CRPC is recommended for patients with metastatic disease.
  • For patients receiving intermittent ADT, rising PSA levels during the off-treatment interval occur normally, prompting re-initiation of therapy, usually when the PSA reaches a level of 10–20 ng/ml.
  • The described approaches may also apply in the treatment of locally advanced/high-risk disease with or without local therapy.