Redefining Clinically Significant Castration Levels in Patients with Prostate Cancer Receiving Continuous Androgen Deprivation Therapy

BERKELEY, CA ( - Many men on androgen deprivation therapy (ADT) for prostate cancer (CaP) may not be achieving adequate levels of castration according to a report in the October, 2007 issue of the Journal of Urology.

Researches in Barcelona, Spain determined testosterone castration levels in men on continuous ADT and correlated this with disease outcomes.

LHRH agonist is historically considered adequate in CaP patients with the testosterone level is <50ng/dl. However, a level <20ng/dl as seen in men undergoing surgical castration may be more appropriate. In this study, the rate of breakthrough increase in serum testosterone in patients receiving 3 months of depot LHRH agonist according to the proposed level of 20ng/dl and the classic LHRH agonist level of 50ng/dl was assessed. The authors’ primary objective was to determine the lowest level of serum testosterone castration level with clinical relevance – the endpoint being survival free of androgen independent CaP (AICaP). In those men with breakthrough increases in serum testosterone, the benefit of adding bicalutamide was analyzed.

A cohort of 77 men with nonmetastatic CaP on ADT had PSA and testosterone routinely checked. ADT was given either as primary treatment (in 68.5%) or as adjuvant or salvage therapy in 31.5%. Bicalutamide was continued as combination therapy in 28 men. Mean follow-up after initiation of ADT was 54 months. An increase in serum testosterone >20ng/ml was considered a breakthrough. The patients were classified in 3 groups: group 1 was all testosterone determinations <20ng/dl, group 2 was patients with breakthrough increases of testosterone between 20 and 50 ng/dl, and group 3 was defined as patients with breakthrough increases >50ng/ml.

Based upon testosterone levels, 33 patients were in group 1, 23 patients were in group 2, 18 men were in group 3, and 3 men had all testosterone levels >50ng/dl. Multivariate analysis demonstrated that a breakthrough of testosterone >50ng/dl was the only predictive factor of worse survival free of AICaP. Groups 1, 2, and 3 had mean survival free of AICaP of 106 months, 90 months, and 72 months, respectively. The lowest serum testosterone level that was able to significantly distinguish groups related with the survival free of AICaP was 32ng/dl. If all testosterone levels checked were <32ng/dl, the survival free of AICaP was 137 months compared to 88 months for patients with any breakthrough increase >32ng/dl. Patients on bicalutamide as maximal androgen blockade had similar testosterone breakthroughs >50ng/dl, but significantly longer survival free of AICaP (115 months v. 32 months).

Morote J, Orsola A, Planas J, Trilla E, Raventós CX, Cecchini L, Catalán R

J Urol. ePub: August 15, 2007