Staging of prostate cancer with complex PSA and complex PSA indices, free PSA ratio, PSAD and PSA-TZ: Results of the prospective european prostate cancer detection and staging study

721

722

BLOOD LEVELS OF FREE-PSA, BUT NOT COMPLEXED-PSA, CORRELATE TO LEVELS OF PSA IN SEMINAL FLUID CONTRIBUTED BY THE PROSTATE GLAND IN HEALTHY YOUNG MEN

STAGING OF PROSTATE CANCER WITH COMPLEX PSA AND COMPLEX PSA INDICES, FREE PSA RATIO, PSAD AND PSA-TZ: RESULTS OF THE PROSPECTIVE EUROPEAN PROSTATE CANCER DETECTION AND STAGING STUDY

mC.‘,

Diavan B.‘, Zlotta A.R.‘, Horninger W.‘, Ravery V.‘, Hammerer P.‘, Kaisary A!, Dobronskl P.‘, Reissigl A.“. Remzi M.‘, Schubnan C.C.‘, Boccon Gibod L.‘, Bartsch G.‘, Marberger M.’

Giwercman

‘MalmG University, ‘Malmii University, University, University

Y.‘, Richthoff

J.‘, Malm J.‘, Giwercman

A.‘, Lilja H.’

University Hospital, Clinical Chemistry, MalmB, Sweden, University Hospital, Urology, MalmG, Sweden, ‘MalmG Hospital, Scanian Andrology Centre, MalmG, Sweden

INTRODUCTION

& OBJECTIVES: Prostate-specific antigen (PSA) from the prostate gland epithelium is secreted at high concentrations into seminal fluid where it is predominately found as a free active enzyme. In blood, normal levels of PSA correspond to l/l0 million of those in seminal fluid. The majority of PSA in blood is covalently linked to alpha-1-antichymotrypsin (complex-PSA), whereas free, noncomplexed PSA-forms constitute 5-45% of the immunodetectable total PSA. The objective of this study was to investigate in young healthy men whether levels of freeand complex-PSA in serum are associated with the levels of PSA released by the prostate gland into seminal fluid. MATERIAL & METHODS: Free-, and total-PSA concentrations m serum and seminal plasma were measured in 202 volunteer male army conscripts in Southern Sweden (age group 18-21 years).

RESULTS: We found a significant

correlation in levels of free-PSA in serum to the concentration of PSA (r=0.42, p
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CONCLUSIONS: This is the first study ever reported to show that in young healthy males, free, non-complexed PSA-forms in serum show a weak (I 7% co-variation), but’statistically highly significant correlation to concentrations of PSA in seminal plasma. In contrast, levels of complex-PSA in blood are not associated to the levels of PSA in seminal fluid. Complex-PSA levels in serum may therefore be concluded to mainly depend on manifestations of prostate disease, whereas free PSA-levels depend on the normal physiological function of the prostate gland.

‘University of Vienna, Urology, Vienna, Austria, ‘University of Brussels, Urology, Brussels, Belgium, ‘University of Innsbruck, Urology, Innsbruck, Austria, ‘University of Paris. Urology, Paris, France. ‘University of Hamburg, Urology, Hamburg, Germany, ‘University of London, Urology, London, United Kingdom, ‘University of Warsaw, Urology, Warsaw. Poland, “LKH Bregenz. Urology, Bregenz, Austria INTRODUCTION & OBJECTIVES: Complex PSA(cPSA) has been recently introduced as a new marker for early prostate cancer detection and prospectively evaluated in 2 large multicenter trials (the US and the European trial). Little is known on the value of molecular forms of PSA for prostate cancer staging. The purpose of our study was to evaluate the value of this newly developed markers to predict the pathological stage following radical prostatectomy. MATERIAL & METHODS: In this prospective multicenter European study a total of 1228 men were included. In this group, 33% were found to have prostate cancer and 67% were found to have BPH. A total of 121 men with clinically localised prostate cancer underwent radical prostatectomy so far and data were available for the analysis. Serum PSA, %free PSA ratio, cPSA, cPSA density, cPSA density of transition zone, c/t PSA ratio, c/free PSA ratio, PSAD, PSA-TZ, DRE and PSA velocny were determined and the ability of these parameters to predict extracapsular disease in the surgical specimen was evaluated using univariate or multivariate as well as an artificial neural network (ANN), based on an advanced multiplayer perception selected for accuracy by a genetic algorithm. RESULTS: A total of 69/ 121 patients (57.0%) had pathologically organ confined prostate cancer while 52 of 218 (43%) had extracapsular disease. Complex PSA levels were significantly higher in extracapsular disease than organ confined cancers (4.84 versus 7.49 ngiml./cc, p
723 CAN COMPLEXED PSA IMPROVE THE PROSTATE CANCER DETECTION RATE IN MEN WITH A “NON-SUSPICIOUS” TOTAL PSA ANGE BELOW 4 NC/ML? - RESULTS OF A MULTICENTER TRIAL Kwiatkowski M.‘. Lein M.‘. Semjonow A.‘. Hammerer Schnorr D.‘, Loening S.A.‘, Sinha P.‘, Jung K.’

P.‘. Luboldt

H.J.‘, Reeker F.‘.

‘Cantonal Hospital Aarau, Department of Urology, Aarau, Switzerland, ‘University Hospital Charitt. Department of Urology, Berlin, Germany, ‘University Hospital, Department of Urology, Miinster, Germany. ‘University Hospital, Department of Urology. Hamburg. Germany. ‘Medical School Essen, Department of Urology, Essen, Germany INTRODUCTION & OBJECTIVES: It has been suggested that the determination of complexed prostate-specific antigen (cPSA) using a recently introduced new test, IS superior in prostate cancer (PCs) diagnosis compared to total-PSA (t-PSA) or the free to total-PSA ratio (f/t-PSA). To evaluate the diagnostic utility of PSA forms in the low t-PSA range (O.Ol3.99 ng/mL) a large multicenter trial was performed. MATERIAL& METHODS: 510 subjects (178 PCs patients and 332 men with BPH) with total PSA O-4 ng/ml from 5 centres in Germany and Switzerland underwent a multi-sector needle biopsy of the prostate. T-PSA and F-PSA were determined with the PSA and Free PSA Immunoassay (Roche Diagnostics, Mannheim, Germany). The t-PSA concentrations were also measured with the Bayer Immune 1 PSA Assay (Bayer Diagnostics, Tarrytown, NY). cPSA was performed using an immunoassay for the Bayer Immune 1 system. The diagnostic validity was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In both groups studied, t-PSA values differ sigmficantly (PCs 2.59*1.0 ng/mL; (mean*SD) vs. BPH 2.07-tl.02). ROC curve analyses were performed to compare the clinical validity within the t-PSA ranges 0 to 4 ng/mL, 0 to 2.5 ng/mL, and 2.5 to 4 ng/mL. No statistical differences were observed between the AUC for the studied PSA forms in the t-PSA range of 0 to 4 ng/mL nor in the range of 0 to 2.5 ng/mL. Within the selected t-PSA range of 2.5 to 4 ng/mL only the AUC for cPSA (0.607) was significantly larger than the AUC for t-PSA measured with Roche (0.507; p=O.OlS) or Bayer (0.542; p=O.O48) assay. The ratios of cPSA to t-PSA (c/t-PSA) or fit-PSA were not superior to the diagnostic discriminative power of t-PSA. For t-PSA range of 2.5 to 4 ng/mL sensitivity and specificity at various cutoffs were calculated. E.g., at 95% specificity the sensitivity of t-PSA (Bayer) being 16% did not signiticantly differ from that of cPSA (20%) or f/t-PSA (I 1%). At 95% sensitivity the specificity of t-PSA (Bayer) being 4% did not significantly differ from that of cPSA (1%) or fit-PSA (6%). CONCLUSIONS: This analysis shows that neither cPSA alone nor the ratios of cPSA or fPSA to t-PSA were suffXently able to discriminate between the PCs and BPH group. In this study the novel cPSA assay could not improve the detection rate of PCs in men with a t-PSA values ~4 ng/mL. The search for a clinically useful serum marker to identify PCs in men with low t-PSA concentrations must continue and remains a special challenge for the near future.

724 PREDICTING CANCER ON REPEAT BIOPSY: RESULTS OF A MULTICENTER PROSPECTIVE EVALUATION OF COMPLEXED PSA Bartsch G.‘, Brawer M ‘. Cheh C.‘. Horninger W.‘. Babalan R ‘, Frltsche H 0 Tane~a S ‘_Leper H ~. (‘hIIds S.“, Stamcy T:. Sokoll L..“.(‘ban D “, Parnn A * ‘Universtty of Innsbruck, Urology, Innsbruck. Austna. ~Northwest Prostate Institute, Bayer, Tarrytown, United States of America, ‘Bayer Corporanon, Bayer, Tarrytown, United States of America, ‘M.D.Anderson Hospital, Urology, Houston. United States ofAmerica. ‘NYU School of Medicine. Urology, New York, United States of America. “Wyoming Research Foundation, Urology, Wyoming, United States of America, ‘Stanford University, Urology, San Francisco, Umted States of Amertca, “The Johns Hopkms Institutes, Urology, Baltimore, Umted States of AtnerGi INTRODUCTION & OBJECTIVES: Approximately 20% of men undergoing a prostate biopsy will be shown on repeat biopsy to have prostate cancer (Cap). Thus, alternate strategies are needed to enhance cancer detection and minimize false positive biopsies. We conducted a multicenter prospective evaluation of Complexed PSA (cPSA). As part of this evaluation, we enrolled men indicated for a repeat biopsy and sought to compare the diagnostic performance of cPSA in comparison to tPSA, the free/total PSA ratio (f/tPSA) and complexed/total PSA ratio (c/tPSA). MATERIAL & METHODS: Men undergoing repeat biopsy consisting of > IO prostate tissue cores after an initial negative biopsy were prospectively enrolled at each of 7 evaluation sites. Serum was collected and tested wth the Bayer lmmunol tPSA and cPSA methods and Beckman Access fPSA and tPSA methods. Receiver Operating Characteristic (ROC) curve analysis was performed and the area under the c”rve (AUC) was calculated for tPSA, cPSA and PSA ranos. RESULTS: 264 men were evaluated and 91 (34%) had carcinoma detected on repeat biopsy. Median PSA values for men with CaP were 7.85 ng/mL and for those wth benign disease was 7.15 ng/mL. ROC analyst Indicated that the AUC for tPSA, cPSA, f/tPSA and c/tPSA were ,567, .583, 648, and ,666, respectively. The AUC for cPSA was statlstically greater than tPSA (p-.017) and c/tPSA provided a statistically significant improvement I” the AUC over cPSA (p=.O3). The AUC for f/tPSA was not statistically greater than cPSA (p=. IO). The table shows the significant findings with respect to sensitivity and specificity CONCLUSIONS: These data indicate that the use of cPSA may be useful as a tirst line test for CaP detection over traditional tPSA testing. c/tPSA further improved speclticity at climcally relevant sensitivity for CaP detection and outperformed f/tPSA. Use of c/tPSA can ald in selecting men Indicated for reueat bioosv orocedure.

I 95 tPSA

cutoff ng/mL SPCC%

cPSA % free PSA % cPSA spec %

cutoff ngimL spec % cutoff ng/mL spec % cutoff ng/rnL

4.1 14.5 3.4 16.2 20.9 I5 14.6 173

I90 4.5 18.5 3.7 20.8 18.4 23.1 77.2 26

1 Sensitivity (%) I 85 4.8 22 4 21.2 17.3 2X.3 79 36.4

1 1 80 5.5 29.5 4.4 28.9 16.1 38.7 80 40.5

I 15 5.9 32.9 4.9 36.4 15.1 46.8 81.6 48

European Urology Supplements 2 (2003) No. 1, pp. 183