Another group who convened a similar roundtable of experts concluded that “assessment of patients receiving LHRH agonists should be based on PSA levels rather than serum testosterone levels, although levels of serum testosterone similar to those obtained after orchiectomy still need to be achieved.”37 Several other authors have suggested that the castrate testosterone level needs to be redefined based on modern testosterone Inhibitors,research,lifescience,medical assay techniques.14,36,38,39

Based on the most contemporary literature, the current castrate level is defined as lower than 50 ng/dL. The older assay technique for the determination of serum testosterone was known as the double isotope derivative dilution method. This traditional assay was prone to error with lower testosterone levels. Current techniques use the chemoluminescent assay that is reported to be more robust at lower testosterone levels.40 Using chemiluminescent techniques, testosterone values of 16 ng/dL (0.55 nmol/L) and 15 ng/dL (0.5 nmol/L) were reported after bilateral orchiectomy.14,41 Inhibitors,research,lifescience,medical A general consensus now exists that testosterone levels achieved and maintained with LHRH agonist therapy should be equivalent to surgical castration.25,36 Inhibitors,research,lifescience,medical Currently unknown is the absolute minimal level of testosterone necessary to effectively prevent prostate cancer growth and progression. The issue of optimum testosterone

levels and androgen suppression escape has been recently evaluated by Morote.39 He and his colleagues performed a study of 73 men with nonmetastatic prostate cancer with serial PSA and testosterone measurements treated with LHRH androgen suppression. They were stratified into tertiles (testosterone < 20, 20–50, and > 50 ng/dL). The best outcomes in preventing androgen- these independent Inhibitors,research,lifescience,medical prostate Inhibitors,research,lifescience,medical cancer progression occurred at a breakpoint of 32 ng/dL. Breakthrough increases greater than this threshold predicted a lower survival free of androgen-independent progression. There was a 137-month versus an 88-month

difference in progression to androgenindependent prostate cancer favoring the lower mean testosterone level. Men who maintained a serum PSA level of lower than 20 ng/dL had a mean PSA progression-free survival of 106 months versus 90 months for those with levels between 20 and 50 ng/mL and only 72 months if the mean serum PSA level was higher Carfilzomib than 50 ng/mL. This study also suggested that maximal androgen blockade might benefit medically castrated cases of prostate cancer with breakthrough testosterone increases of higher than 50 ng/dL. A similar concept has been reported by Perachino and associates.42 In a series of 162 men with metastatic prostate cancer, a multivariate approach defined the best prognostic model for survival based on 6-month testosterone levels of men treated with goserelin. Using the lower than 50 ng/dL medical castration threshold, 119 patients (73.