Neue Biomarker und Anwendung multivariater Modelle zur Detektion des Prostatakarzinoms

Zusammenfassung

Molekulare Formen des prostataspezifischen ­Antigens (PSA) und des freien PSA (fPSA) wie das prozentuale freie PSA (%fPSA), proPSA, intaktes PSA oder das BPHA und andere neue Marker können die diagnostische Spezifität des PSA verbessern. Bei vielen der neuen Marker wie EPCA2 im Serum oder Annexin A3 (ANXA3) im Urin konnten die ersten guten Ergebnisse bisher noch nicht ­bestätigt werden bzw. es zeigte sich nur eine marginale Verbesserung der Spezifität. Andere Urinmarker wie das PCA3 oder das TMPRSS2-ERG Genfusionsprodukt haben das Potenzial, bevorzugt aggressive Tumoren zu entdecken und die Rate unnötiger Prostatabiopsien zu senken. Die Kombination dieser neuen Urinmarker mit etablierten Serummarkern könnte zukünftig eine weitere Spezifitätsverbesserung des Gesamt-PSA (tPSA) bewirken. Durch den Einsatz multivaria­ter Modelle wie z. B. artifizielle neuronale Netzwerke (ANN) oder auf logistischer Regression (LR) ­basierte Nomogramme, die eine kombinierte und gleichzeitige Bewertung verschiedener Marker ermöglichen, ist in dieser Hinsicht ein wei­terer Fortschritt zu erzielen. Diesen deutlichen Vorteil der multivariaten Bewertung gegenüber der Anwendung einzelner Parameter hat bereits die Nutzung des %fPSA innerhalb von ANN- und LR-Modellen gezeigt. In dieser Übersichtsarbeit werden neue Marker zur Detektion des Prostatakarzinoms (PCa) und deren Einsatz innerhalb multi­variater Modelle eingeschätzt.

Abstract

The specificity of PSA has been enhanced by using molecular forms of PSA and free PSA (fPSA) such as percent free PSA (%fPSA), proPSA, intact PSA or BPHA and / or new serum markers. Most of these promising new serum markers like EPCA2 or ANXA3 still lack confirmation of the outstanding initial results or show only marginally enhanced specificity at high sensitivity levels. PCA3, TMPRSS2-ERG, and other analytes in urine col­lect­ed after digital rectal examination with ap­pli­ca­tion of mild digital pressure have the potential to preferentially detect aggressive PCa and to ­decrease the number of unnecessary repeat biop­sies. The combination of these new urinary mark­ers with new and established serum markers seems to be most promising to further increase specificity of tPSA. Multivariate models, e. g., artificial neural networks (ANN) or logistic regression (LR) based nomograms have recently been per­formed by incorporating these new markers in several studies. There is generally an advantage to include the new markers and clinical data as additional parameters to PSA and %fPSA within ANN and LR models. Results of these studies and also unexpected pitfalls are discussed in this ­review.

Schlüsselwörter

Prostatakarzinom - Diagnostik - PSA - Biomarker - multivariate Modelle

Key words

prostate cancer - diagnosis - PSA - biomarkers - multivariate models

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