Rapid elimination kinetics of free PSA and hK2 following initiation of GnRH-antagonist treatment of aggressive Prostate Cancer.
Ulmert D., Serio A., Scher HI., Seandel M., Frankel D., Vickers A., Kold Olesen T., Lilja H.
5171 Background: Presently the sum (tPSA) of complex (cPSA) and free PSA (fPSA) is used when evaluating the effect of prostate cancer treatment. PSA-forms display large discrepancies in metabolic pathways and elimination rates from blood due to significant differences in size, character and treatment. Prior studies of serial blood samples taken subsequent to radical prostatectomy (RP) showed that cPSA decrease is very slow as opposed to fPSA that is rapidly eliminated in exponential fashion. Previous studies of GNRH-agonist treated patients showed that all prostate kallikrein forms decrease in a similarly slow exponential manner. Access to serial samples taken after treatment with a novel GnRH-antagonist (Degarelix) allowed us to investigate the elimination profile of prostate kallikrein-forms after the rapid castration induced by this drug. MATERIAL AND METHODS: Serial bloods (1, 3, 7, 14, 21 and 28 days after treatment initiation) were from 24 prostate cancer patients following the initiation of treatment with the GnRH-antagonist. 2/24 had localized disease, 15/24 locally advanced, 6/24 generalized and 1/24 was non-classified. PSA-forms were measured with a commercial assay and hK2 with a research prototype assay. RESULTS: Geometric mean levels (ng/mL) of tPSA, cPSA, fPSA and hK2 at baseline were 42.6 (SD 48.0), 36.5 (SD 36.5), 6.10 (SD 7.99) and 1.30 (SD 2.84), respectively. 22/24 patients had castrate levels (<0.5 ng/ml) after 24 hours, and 24/24 after 72 hours. All kallikrein-forms declined in an exponential fashion after degarelix administration, a much faster elimination rate could be observed for free PSA and hK2 compared to tPSA (or cPSA). At day 3 and day 7, the percent decline in hK2 and fPSA from pre-treatment levels was significantly higher than that of tPSA (or cPSA). CONCLUSION: The fast onset of action of the GnRH-antagonist and the subsequent decline in PSA lead to a profile in the reduction of prostate kallikreins that is similar to the decline seen after RP. The faster decline of free forms reflects the effect of testosterone elimination more accurately and promptly than tPSA. Monitoring with fPSA and hK2 may provide more reliable option to assess response to treatment after rapid onset of castration. [Table: see text].