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Incomplete testosterone suppression with luteinizing hormone-releasing hormone agonists: does it happen and does it
Tom Pickles1, Jeremy Hamm, W James Morris
1Radiation Programme, BC Cancer Agency, and Department of Radiotherapy and Developmental Radiotherapeutics, University of British Columbia, Vancouver, Canada. tpickles@bccancer.bc.ca
BJU International
|May 9, 2012
Summary
Luteinizing hormone-releasing hormone (LHRH) agonist therapy for prostate cancer can lead to testosterone suppression breakthroughs, particularly in younger men. Monitoring testosterone levels during treatment is advised due to potential adverse effects on cancer control.
Area of Science:
- Urology
- Oncology
- Endocrinology
Background:
- Incomplete testosterone suppression, defined as levels >1.1 or 1.7 nmol/L, has been reported with LHRH agonists in small patient groups.
- Predisposing factors may include drug type, patient age, pretreatment testosterone, and weight.
- Previous studies suggest incomplete suppression is linked to increased PSA failure rates and worse survival in metastatic disease.
Purpose of the Study:
- To determine breakthrough rates of testosterone suppression above castrate levels in men receiving adjuvant LHRH agonist therapy with curative radiation.
- To investigate factors predisposing to these breakthroughs and their impact on oncological outcomes.
Main Methods:
- A population-based series of 2196 men treated for prostate cancer with curative radiation and LHRH therapy between 1998 and 2007 in British Columbia, Canada.
- Serial testosterone measurements were analyzed during continuous LHRH therapy.
- Breakthrough rates (>1.1 and >1.7 nmol/L) were calculated per injection and per patient course; predisposing factors and early oncological outcomes were assessed.
Main Results:
- Breakthrough rates per patient course were 6.6% (>1.1 nmol/L) and 3.4% (>1.7 nmol/L).
- Younger age was significantly associated with breakthrough risk (P < 0.001); increasing BMI had a minor effect.
- Repeated breakthroughs occurred in 16% of patients. Early PSA kinetic surrogates of cancer control were inferior in those with breakthroughs, and 5-year biochemical non-evidence of disease (bNED) was worse in a subgroup with breakthroughs between 1.1-1.7 nmol/L.
Conclusions:
- Testosterone suppression breakthroughs occur with LHRH agonists, impacting early outcome measures.
- Monitoring testosterone levels during LHRH agonist therapy is recommended.
- While overall survival and bNED were not compromised, specific breakthrough levels may affect long-term outcomes.
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