Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular kallikrein 2 in clinically localized prostate cancer before and after radical prostatectomy

Purpose: We studied plasma concentrations and elimination rates of prostate specific antigen (PSA) complexed to alpha 1-antichymotrypsin and alpha 2-m acroglobulin, free PSA, total PSA (free PSA plus PSA al-antichymotrypsin) a nd human glandular kallikrein 2 before, during and after radical retropubic prostatectomy for clinically localized prostate cancer. Materials and Methods: Plasma was collected and frozen within 10 minutes af ter sampling from 18 patients undergoing radical retropubic prostatectomy f or prostate cancer. One sample was drawn preoperatively. Subsequent samplin g intervals were 5 to 20 minutes perioperatively, 2 to 4 hours during the f irst 12 postoperative hours and 24 to 48 hours until postoperative day 14. Free PSA, PSA alpha 1-antichymotrypsin total PSA, PSA alpha 2-macroglobulin and human glandular kallikrein 2 were measured with time resolved immunofl uorometric assays. Results: Preoperatively PSA alpha 2-macroglobulin was undetectable (less th an 2 ng./ml.) in 17 of 18 patients. Human glandular kallikrein 2, free PSA and total PSA but not PSA arl-antichymotrypsin were significantly higher in patients with extraprostatic cancer (pT3a-pT4a, pN1) compared to those wit h organ confined cancer (pT2a/b). Surgical manipulation of the prostate cau sed no detectable elevation of human glandular kallikrein 2, PSA alpha 1-an tichymotrypsin or PSA alpha 2-macroglobulin. In contrast, a mean 9.6-fold i ncrease (range 3.4 to 22) in free PSA was noted 5 minutes after prostatecto my. Free PSA was eliminated from plasma in a biphasic exponential pattern w ith an early plasma half-life of 55 minutes and a late plasma half-life of 18 hours. PSA alpha 1-antichymotrypsin decreased slowly, whereas human glan dular kallikrein 2 was detectable only 12 hours after prostatectomy. PSA al pha 2-macroglobulin remained at insignificant, nondetectable concentrations during the entire perioperative and postoperative period. Conclusions: Release of free PSA contributes to the elevation of plasma tot al PSA after prostatectomy. Free PSA is enzymatically inactive as the relea se does not result in subsequent elevation of PSA al-antichymotrypsin or PS A alpha 2-macroglobulin. Biphasic exponential elimination of free PSA may b e explained by rapid extracellular redistribution (early half-life) and glo merular filtration in the kidneys (late half-life). Our data suggest rapid metabolism of human glandular kallikrein 2 but do not support suggestions o f the significance in vivo of complex formations with alpha 2-macroglobulin as a major means to eliminate PSA from plasma in patients with clinically localized prostate cancer.