Tibor Szarvas1,2,3, Sabina Sevcenco2, Orsolya Módos1, Dávid Keresztes1, Péter Nyirády1, Anita Csizmarik1, Robin Ristl4, Martin Puhr5, Michèle J Hoffmann6, Christian Niedworok3, Boris Hadaschik3, Agnieszka Maj-Hes2, Shahrokh F Shariat2, Gero Kramer2. 1. Department of Urology, Semmelweis University, Budapest, Hungary. 2. Department of Urology, Vienna General Hospital, Medical University Vienna, Vienna, Austria. 3. Department of Urology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany. 4. Centre for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. 5. Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria. 6. Department of Urology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Abstract
OBJECTIVE: To assess the predictive value of pre-chemotherapy matrix metalloproteinase 7 (MMP-7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy. PATIENTS AND METHODS: Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 patients with castration-resistant prostate cancer (CRPC): 21 docetaxel-resistant patients who received one single series and 75 docetaxel-sensitive patients who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. RESULTS: Higher pretreatment serum MMP-7, sFas and prostate-specific antigen (PSA) levels were significantly associated with both docetaxel resistance (P = 0.007, P = 0.001, P < 0.001, respectively) and shorter cancer-specific survival (P < 0.001, P = 0.041, P < 0.001, respectively). High MMP-7 level remained an independent predictor of both docetaxel resistance (hazard ratio [HR] 2.298, 95% confidence interval [CI]: 1.354-3.899; P = 0.002) and poor cancer-specific survival (HR 2.11, 95% CI: 1.36-3.30; P = 0.001) in multivariable analyses. Greater increase in MMP-7 levels in the second treatment holiday and greater increase in PSA levels in the first and second treatment holidays were predictive of survival. CONCLUSIONS: Pretreatment serum MMP-7 levels may help to select patients with CRPC who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 levels alone or in combination with PSA levels could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making.
OBJECTIVE: To assess the predictive value of pre-chemotherapy matrix metalloproteinase 7 (MMP-7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy. PATIENTS AND METHODS: Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 patients with castration-resistant prostate cancer (CRPC): 21 docetaxel-resistant patients who received one single series and 75 docetaxel-sensitive patients who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. RESULTS: Higher pretreatment serum MMP-7, sFas and prostate-specific antigen (PSA) levels were significantly associated with both docetaxel resistance (P = 0.007, P = 0.001, P < 0.001, respectively) and shorter cancer-specific survival (P < 0.001, P = 0.041, P < 0.001, respectively). High MMP-7 level remained an independent predictor of both docetaxel resistance (hazard ratio [HR] 2.298, 95% confidence interval [CI]: 1.354-3.899; P = 0.002) and poor cancer-specific survival (HR 2.11, 95% CI: 1.36-3.30; P = 0.001) in multivariable analyses. Greater increase in MMP-7 levels in the second treatment holiday and greater increase in PSA levels in the first and second treatment holidays were predictive of survival. CONCLUSIONS: Pretreatment serum MMP-7 levels may help to select patients with CRPC who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 levels alone or in combination with PSA levels could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making.