Similar rates of exponential decrease in serum concentrations of free prostate-specific antigen (PSA), PSA complexed to alpha-1-antichymotrypsin, and human glandular kallikrein 2 (hK2) in prostate cancer patients treated with GnRH-analogues.
BACKGROUND
Our recently reported finding of rapid bi-exponential elimination of free prostate-specific antigen (PSA) after radical retropubic prostatectomy in patients with moderately elevated PSA levels, which contrasted a very slow, linear elimination of PSA complexed to alpha-1-antichymotrypsin (ACT), prompted us to study whether these elimination rates were applicable for patients selected for castration treatment with very high pretreatment concentrations of PSA in serum. In addition, serum concentrations of hK2, the activator of proPSA, were measured.


METHODS
Pretreatment serum was obtained from 21 previously untreated prostate cancer patients due for hormonal treatment with a GnRH-analog. Samples were also collected during treatment up to a minimum of 24 weeks at 2-week intervals and analyzed with immunofluorometric assays for free PSA (PSA-F), PSA complexed to alpha-1-antichymotrypsin (PSA-ACT), total PSA (PSA-T), and human kallikrein 2 (hK2). For pharmaco-kinetic analysis the serum concentrations of hK2 and PSA forms for each patient were plotted against time both before and after logarithmic transformation and the half-lives were calculated as ln2/k.


RESULTS
Median pretreatment serum concentrations were 322 ng/ml (range, 1.9-2210) for PSA-T, 27.8 ng/ml (range, 1.14-259) for PSA-F, and 207 ng/ml (range, 0.8-2080) for PSA-ACT. All patients had castrate levels of serum testosterone (< 2.5 nmol/l) in less than 21 days after initiation of GnRH-analog treatment. It was possible to evaluate data from 19/21 patients which showed an exponential decrease of all PSA concentrations in serum, with mean half-lives of 12.9 days (range, 7.3-30) for PSA-T, 15.5 days (range, 7.7-37.5) for PSA-F, and 12.3 days (range, 6.6-30) for PSA-ACT. Median pretreatment percent free PSA (PSA-F/PSA-T) was 12% compared to 18% at nadir. The median pretreatment level of hK2 was 3.5 ng/ml (range, 0.29-30.3). There was an exponential decrease in hK2 concentrations in serum after initiation of hormonal treatment with a mean half-life of 18.7 days (range, 7.5-37.5).


CONCLUSIONS
For the majority of patients with hormonally treated prostate cancer the serum concentrations of PSA-T, PSA-F, PSA-ACT, and hK2 decreased slowly in parallel and mono-exponentially after initiation of treatment. Mean half-lives were between 12 and 19 days.
Björk
T
T
Department of Urology, Malmö and Lund University Hospitals, Lund University, Malmö, Sweden. thomas.bjork@kir.mas.lu.se
Schalken
J
J
Wittjes
W
W
Ljungberg
B
B
Lilja
H
H
D000368:Aged; D000369:Aged, 80 and over; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000601:surgery; D020840:Tissue Kallikreins / Q000097:blood*; D000514:alpha 1-Antichymotrypsin / Q000097:blood*
D000514:alpha 1-Antichymotrypsin; D007987:Gonadotropin-Releasing Hormone; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen