Human glandular kallikrein 2 levels in serum for discrimination of pathologically organ-confined from locally-advanced prostate cancer in total PSA-levels below 10 ng/ml

Background. We measured serum levels of human glandular kallikrein 2 (hK2) in patients treated with radical retropubic prostatectomy (rrP) for clinica lly localized prostate cancer (PCa) with a total PSA (tPSA)-level below 10 ng/ml to investigate whether hK2 can be applied to preoperatively distingui sh organ-confined (pT2a/b) from nonorgan-confined (greater than or equal to pT3a)-PCa more accurately than total PSA. Further, we evaluated hK2, free- and tPSA-concentrations in all pathologic stages of PCa. Methods. 161 serum samples from men scheduled for rrP were collected 1 day before surgery prior to any prostatic manipulation. Pathologic work-up reve aled greater than or equal to pT3a-PCa in 48 and pT2a/b-PCa in 113 patients . HK2-levels in serum were measured using an immunofluorometric assay with an analytical sensitivity of 0.5 pg/ml, a functional sensitivity of 5 pg/ml and insignificant cross-reactivity with PSA (<0.005%). Total (tPSA) and fr ee PSA (fPSA) levels were measured using a commercially available assay fro m which we calculated %fPSA and an algorithm that combined hK2 and PSA-leve ls [hK2] x [tPSA/fPSA]. Means, medians, and ranges were calculated for pT2a /b vs. <greater than or equal to>pT3a-PCa and for all pathologic stages. St atistical significance of differences was calculated using Mann-Whitney-U a nd Kruskal-Wallis tests. Calculation of receiver-operator-characteristic (R OC) curves were performed for hK2, [hK2] x [tPSA/fPSA] and tPSA to compare diagnostic performance. Results. A mean tPSA level in serum of 6.12 ng/ml in greater than or equal to pT3a-PCa was not significantly different (P=0.366) from 5.78 ng/ml in pT 2a/b-PCa. Also, there were no statistically significantly different levels of fPSA (P=0.947) or %fPSA (0.292) for these two groups. By contrast, mean hK2-level in pT2a/b-PCa of 80 pg/ml was significantly different (P=0.004) f rom a mean hK2 level of 120 pg/ml in greater than or equal to pT3a-PCa as s hown by Mann-Whitney-analysis Moreover, the algorithm of [hK2] x [tPSA/fPSA ] was significantly lower (P=0.0004) in pT2a/b-PCa vs. greater than or equa l to pT3a-PCa. Calculation of areas under curve (AUC) by receiver-operator- characteristics (ROC) demonstrated that the AUC for hK2 (0.64) was larger a nd the AUC for [hK2] x [tPSA/fPSA] (=0.68) significantly larger (P=0.007) c ompared to the AUC of tPSA (0.55). Furthermore, Kruskal-Wallis Test revealed a highly significant correlation to pathologic stage using hK2 (P=0.008) and [hK2] x [tPSA/fPSA] (P=0.0015) compared to no significant differences in serum concentration of tPSA (P=0. 296). Also at tPSA-levels from 10-20 ng/ml, the hK2-levels in pT2a/b-PCa we re close to significantly different (P=0.051) from those in men with greate r than or equal to pT3a-PCa, while the algorithm of [hK2] x [tPSA/fPSA] in that tPSA-range was significantly lower (P=0.002) in pT2a/b-PCa compared to greater than or equal to pT3a0-PCa. Conclusion. Highly significant differences in serum concentration enable hK 2 to be a powerful predictor of organ-confined disease and pathologic stage of clinically localized prostate cancer, especially in the PSA-range below 10 ng/ml. As such, there are important clinical consequences for the appli cation of hK2 for the adequate treatment of prostate cancer patients, i.e., the option of nerve-sparing surgery. Prostate 49: 101-109, 2001, (C) 2001 Wiley-Liss, Inc.