Beeinflusst das „Blutplasmavolumen” die Validität von PSA-Tests?

Zusammenfassung

Fragestellung: Lässt sich die Validität eines PSA-basierten Tests verbessern, indem die gemessene Serumkonzentration um den Verdünnungseffekt des individuellen Blutplasmavolumens Vp (oder anderer Körperflüssigkeitsvolumina) korrigiert wird? Materialien und Methoden: Retrospektive Datenanalyse an Patienten mit Prostataadenomektomie (n = 32) oder radikaler Prostatektomie (n = 60) (pT1 - 4 N0 M0). Berechnung von PSA-Density (PSAD) und zwei neuen PSA-basierten Parametern, die das individuelle Vp (nach der von Sprenger modifizierte Retzlaff-Formel) als Korrekturfaktor des t-PSA berücksichtigten (mPSA_Vp, mPSAD_Vp). Analyse der Testvaliditäten von t-PSA, mPSA_Vp, PSAD und mPSAD_Vp (ROC-Kurvenanalyse, Sensitivität, Spezifität, positiver (PPV) und negativer (NPV) Vorhersagewert). Ergebnisse: Tumorstadium und PSA-Werte waren positiv korreliert. Bezogen auf den gesamten t-PSA Bereich (n = 92; 0,1 - 88,4 µg/l) war die Trennschärfe von PSAD (AUC = 0,803) und mPSAD_Vp (AUC = 0,806) signifikant besser (p ≤ 0,003), als von t-PSA und mPSA_Vp (AUC = 0,531), um zwischen P-CA und BPH zu unterscheiden. Im Graubereich (4,0 - 10,0 µg/l) diskriminierten t-PSA (AUC = 0,663), mPSA_Vp (AUC = 0,694) und PSAD (AUC = 0,931) als Test grundsätzlich besser; mPSAD_Vp ergab die höchste AUC (0,947). Die Korrektur um Vp ergab damit insgesamt tendenziell bessere AUC-Werte, ohne dass (bisher) Signifikanzniveau erreicht wurde. Schlussfolgerungen: Die Berücksichtigung von Volumina ist der plausibelste Weg, um die Testvalidität von t-PSA zu steigern. Eine präoperativ verbesserte Bestimmung des Prostatavolumens und seiner benignen und malignen Partialvolumina, sowie eine exakte Berechnung der individuellen Verteilungsvolumina für das t-PSA Molekül im Organismus könnten helfen, die Trennschärfe des t-PSA zu optimieren und kurable Karzinome frühzeitig(er) zu entdecken.

Abstract

Purpose: The aim of this study is to improve the validity of PSA-based tests by considerations of the dilutions caused by the individual plasmatic blood volume (or other relevant body fluids). Materials and Methods: Retrospective analyses of patients who underwent adenomectomy (n = 32) or radical prostatectomy (pT1 - 4 N0 M0; n = 60) were carried out. We calculated the PSA density (PSAD) and two new PSA-based parameters (mPSA_Vp, mPSAD_Vp) that converted t-PSA concentration and PSAD with regard to individual Vp (according to Sprenger's modified Retzlaff formula). Comparative statistics of receiver operating characteristics (ROC-) curves, AUC, sensitivity, specificity, positive and negative predictive values for t-PSA, mPSA_Vp, PSAD and mPSAD_Vp were performed. Results: PSA was positively correlated with local tumour stage. With regard to the whole range of t-PSA (n = 92; 0.1 - 88.4 µg/L) the diagnostic selection between prostate carcinoma (CaP) and benign disease (BPH) was significantly improved by PSAD (AUC = 0.803) and mPSAD_Vp (AUC = 0.806) (p ≤ 0.003) compared to t-PSA und mPSA_Vp (AUC = 0.531). Within the range of 4.0 - 10.0 µg/L PSA, the areas under the ROC curves were much better for t-PSA (AUC = 0.663), mPSA_Vp (0.694) and PSAD (0.931) in gereral; mPSAD_Vp provided the best AUC (0.947). However, although considering Vp does demonstrate better AUCs, this tendency does not reach the level of significance (yet). Conclusions: The most conclusive way to improve PSA test validity is to adjust PSA to different “volumes”. Therefore, elaborated devices for a better preoperative investigation of the whole volume of the prostate gland and its distinct partial volumes (such as carcinoma or benign tissues), as well as applied knowledge on the distribution and kinetics of PSA in body fluids, might substantially help to optimise the detection of curable patients with unknown carcinoma of the prostate.

Schlüsselwörter

Prostatakarzinom - PSA - ROC-Kurven - Sensitivität - Spezifität - Testvalidität

Key words

carcinoma of the prostate - ROC curves - PSA - sensitivity - specificity - test validity

Literatur

• 1 Catalona W J, Smith D S, Ratliff T L, Dodds K M, Coplen D E, Yuan J J, Petros J A, Andriole G L. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer.  N Engl J Med. 1991;  324 1156-1161
• 2 Wang M C, Valenzuela L A, Murphy G P, Chun T M. A simplified purification procedure for human prostate antigen.  Oncology. 1982;  39 1-5
• 3 Sensabough G F. Isolation and characterisation of semen-specific protein from human seminal plasma: a potential new marker for semen identification.  J Forensic Sci. 1978;  23 106-115
• 4 Prestigiacomo A F, Stamey T A. Can free and total prostate specific antigen and prostatic volume distinguish between men with negative and positive systematic ultrasound guided prostate biopsies?.  J Urol. 1997;  157 189-194
• 5 Lilja H, Christensson A, Dahlen U, Matikainen M T, Nilsson O, Pettersson K, Lovgren T. Prostate-specific antigen in human serum occurs predominantly in complex with alpha-anti-chymotrypsin.  Clin Chem. 1991;  37 1618-1625
• 6 Kilic S, Yalcinkaya S, Guntekin E, Kukul E, Deger N, Sevuk M. Determination of the site of metabolism of total, free and complexed prostate-specific antigen.  Urology. 1998;  52 470-473
• 7 Sasagawa I, Nakada T, Hashimoto T, Kubota Y, Hirano K, Hirano J, Suzuki Y. Serum prostatic acid phosphatase, gamma semmino protein and prostate specific antigen in hemodialysis patients.  Urol Int. 1992;  48 181-183
• 8 Catalona W J, Richie J P, Ahmann F R, Hudson M A, Scardino P T, Flanigan R C, Kernion J B de, Ratliff T L, Kavoussi L R, Dalkin B L. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6630 men.  J Urol. 1994;  151 1283-1290
• 9 Stamey T A, Yang N, Hay A R, McNeal J E, Freiha F S, Redwine E. Prostate specific antigen as a serum marker for adenocarcinoma of the prostate.  N Engl J Med. 1987;  317 909-916
• 10 Stamey T A, Kabalin J N, McNeal J E, Johnstone I M, Freiha F, Redwine E A, Yang N. Prostate-specific in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients.  J Urol. 1989;  141 1076-1083
• 11 American Urological Association . Prostate-specific antigen (PSA) best practice policy.  Oncology. 2000;  14 267-272
• 12 Catalona W, Smith D, Ornstein D. Prostate cancer detection of 2.6 to 4.0 ng/ml and Benign Prostate Examination.  JAMA. 1997;  277 1452-1455
• 13 Brawer M K, Chetner M P, Beatie J, Buchner D M, Vessella R L, Lange P H. Screening for prostatic carcinoma with prostate specific antigen.  J Urol. 1992;  147 841-845
• 14 Akduman B, Crawford E D. The PCPT: new findings, new insights, and clinical implications for the prevention of prostate cancer.  Eur Urol Suppl.. 2006;  5 634-639
• 15 Schröder F H, Roobol M J, Damhuis R A, Koning H J de, Blijenberg B G, Kwast T H van der. Rotterdam randomized pilot studies of screening for prostae cancer-an overview after 10 years.  J Natl Cancer Inst. 2005;  97 696-705
• 16 Brawer M K. Prostate cancer: epidemiology and screening.  Prostate Cancer and Prostatic Diseases. 1999;  2 (Suppl.1) 2-6
• 17 Bentvelsen F M, Schröder F H. Modalities available for screening for prostate cancer.  Eur J Cancer. 1993;  29A 804-811
• 18 Hanley J A, McNeil B J. The meaning and use of the area under a receiver operating characteristics (ROC) curve.  Radiology. 1982;  143 29-36
• 19 Zweig M H, Campbell G. ROC plots: a fundamental evaluation tool in clinical medicine.  Clin Chem. 1993;  39 561-577
• 20 Benson M C, Olsson C A. Prostate specific antigen and prostate specific antigen density. Roles in patient evaluation and management.  Cancer. 1994;  74 1667-1673
• 21 Stenman U H, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate-specific antigen and alpha-1-chymo-trypsin is the major form of prostate-specific antigen in serum of patients with prostate cancer: assay of the complex improves clinical sensitivity for cancer.  Cancer Res. 1991;  51 222-226
• 22 Carter H B, Morrel C H, Pearson J D, Brant L J, Plato C C, Metter E J, Chan D W, Fozard J L, Walsh P C. Estimation in prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease.  Cancer Res. 1992;  52 3323-3328
• 23 Sprenger K BG, Huber K, Kratz W, Henze E. Nomograms for the prediction of patient's plasma volume in plasma exchange therapy from height, weight, and hematocrit.  J Clin Apheresis. 1987;  3 185-190
• 24 Harms V. Biomathematik, Statistik und Dokumentation. Harms Verlag 7. Auflage 1998: 34-49
• 25 Hanley J A, McNeil B J. The meaning and use of the area under a receiver operating characteristics (ROC) curve.  Radiology. 1982;  143 29-36
• 26 Griner P F, Mayewski R J, Mushlin A I, Greenland P. Selection and interpretation of diagnostic tests and procedures.  Ann Int Med. 1981;  94 557-592
• 27 Schmid H P. Verbesserung der Spezifität des prostataspezifischen Antigens.  Urologe [B]. 1998;  38 [Suppl 1] 46-48
• 28 Partin A W, Carter H B, Chan D W, Epstein J I, Oesterling J E, Rock R C, Weber J P, Walsh P C. Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia.  J Urol. 1990;  143 747-752
• 29 Babaian R J, Camps J I, Frangos D N, Ramirez E I, Tenney D M, Hassell J S, Fritsche H A. Monoclonal prostate-specific antigen in untreated prostate cancer: Relationship to clinical stage and grade.  Cancer. 1991;  67 2200-2206
• 30 Winter H J, Bretton P R, Herr H W. Preoperative prostate-specific antigen in predicting pathological stage and grade after radical prostatectomy.  Urology. 1991;  38 202-205
• 31 Oesterling J E. Prostate-specific antigen: A critical assessment of the most useful tumor marker for adenocarcinoma of the prostate.  J Urol. 1991;  145 907-923
• 32 Stamey T A, Kabalin J N, McNeal J E, Johnstone I M, Freiha F, Redwine E A, Yang N. Prostate-specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients.  J Urol. 1989;  141 1076-1083
• 33 Veneziano S, Pavlica P, Querze R, Nanni G, Lalanne M G, Vecchi F. Correlation between prostate-specific antigen and prostate volume, evaluated by transrectal ultrasonography: usefulness in diagnosis of prostate cancer.  Eur Urol. 1990;  18 112-116
• 34 Babaian R, Fritsche H A, Evans R B. Prostate-specific antigen.  J Clin Lab Anal. 1990;  4 35-137
• 35 Benson M C, Whang I S, Pantuck A, Ring K, Kaplan S A, Olsson C A, Cooner W H. Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer.  J Urol. 1992;  147 815-816
• 36 Manseck A, Benusch T, Wirth M. Wertigkeit der PSA-Dichtebestimmung beim Prostatakarzinom.  Urologe [A]. 1997;  36 323-326
• 37 Seaman E, Whang M, Olsson C A, Katz A, Cooner W H, Benson M C. PSA Density: Role in patient evaluation and management.  Urol Clin North Am. 1993;  20 653-664
• 38 Beduschi M, Oesterling J. Prostate-specific antigen density.  Urol Clin North Am. 1997;  24 323-332
• 39 Benson M C, Whang I S, Olsson C A, McMahon D J, Cooner W H. The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen.  J Urol. 1992;  147 817-821
• 40 Semjonow A, Hamm M, Rathert P. Prostate volume corrected prostate-specific antigen improves differentiation between benign prostatic hyperplasia and organ-confined prostatic cancer.  Br J Urol. 1994;  73 538-543
• 41 Hoffman B R, Yu H, Diamandis E P. Assay of prostate-specific antigen from whole blood spotted on filter paper and application to prostate cancer screening.  Clin Chem. 1996;  42 536-544
• 42 Wolff J M, Boeckmann W, Borchers H, Handt S, Reineke T, Jakse G. Prostate-specific antigen: insufficient discrimination between benign prostatic hyperplasia and organ-confined prostate cancer.  Urol Int. 1996;  57 170-174
• 43 Shearer R J. Prostatic specific antigen (review).  Br J Urol. 1991;  67 1-5
• 44 Loch T. Innovative approaches in prostate cancer ultrasound.  Urologe A. 2006;  45 692-670