Reviewer: Ryan Smith, MD
Last Modified: June 23, 2002
Authors: T Pickles, A Agranovich, E Berthelet, et al.
Source: Cancer 2002; 94: 362-7
The use of androgen ablation (AA) has become more common in the treatment of prostate cancer. Androgen ablation has a proven survival benefit in patients with advanced (T3-4, or lymph node positive) disease and in those with high Gleason Score (8-10) disease, via the data of large EORTC and RTOG studies. Furthermore, the use of prolonged hormonal ablation (> 2 years) has been shown to be more efficacious than shorter durations of hormones. With the routine use of hormones in these patients, the number of patients receiving androgen ablation therapy is in the thousands per year. There is concern over the risk of permanent gonadal failure in these patients, with subsequent loss of testosterone production and increased late toxicity. This study investigates the recovery of testosterone production following AA.
Hormonal ablation is an essential part of treatment in many patients diagnosed with prostate cancer. However, with more patients being treated with AA, and for longer periods of time, there is concern over the long-term toxicity profiles, mainly dictated by permanent gonadal failure, reflected in testosterone levels. If permanent gonadal failure results, patients would be impotent and at significantly higher risk for osteoporosis, among other things. This study shows that, in the majority of cases this is not a concern, as gonadal function returns within 3 years. In fact, this may simply reflect those patients who would have naturally lost their testosterone production, as shown via the control population. However, though it was stated that longer duration of AA was correlated with less testosterone recovery, there was no data that directly addressing this issue. In fact, only 9 of their patients were treated with over 2 years of AA. As more patients are being treated with 2 to 3 years of AA, this is an important question that needs to be answered. Also, there is no data on symptom recovery (hot flashes, impotence, etc.) as testosterone levels increased after cessation of AA. In addition, patients were scored as recovered if their testosterone rose to normal just once during the analysis period. There is no revision or correction of the data if those patients again dropped below normal. Overall, this study reports encouraging data of testosterone recovery after AA. As long term LHRH agonist therapy has become the standard of care in AA, a prospective study needs to be done to directly address gonadal recovery in these patients.
Mar 23, 2010 - The progression of androgen-dependent prostate cancer to castration-resistant prostate cancer despite androgen ablation therapy is the result of an inflammatory response that enhances tumor cell survival, according to a letter in the March 11 issue of Nature.
Aug 2, 2010
May 26, 2011