BJU International, October 2018, Vol.122(4), pp.695-704
To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.14415/abstract Byline: Tibor Szarvas, Sabina Sevcenco, Orsolya Modos, David Keresztes, Peter Nyirady, Anita Csizmarik, Robin Ristl, Martin Puhr, Michele J. Hoffmann, Christian Niedworok, Boris Hadaschik, Agnieszka Maj-Hes, Shahrokh F. Shariat, Gero Kramer Keywords: MMP-7; Fas; serum; prognosis; docetaxel; #pcsm; #ProstateCancer 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. CAPTION(S): Fig. S1. Kaplan-Meier survival plots stratified by (A) PSA level and presence of metastasis, by MMP-7 in the subgroup of (B) patients with low PSA & and no metastases and (C) patients with high PSA and metastasis. MMP-7 is significantly associated with survival in both subgroups. Fig. S2. Kaplan-Meier curves of overall survival according to (A) MMP-7-, (B) PSA-changes and (C) their combination during the 2nd treatment-free period ( 2nd holiday). Fig. S3. Changes of PSA (blue lines) and MMP-7 levels (red lines) in representative cases of CRPC. Grey area represents treatment periods (series). Note that PSA and MMP-7 levels elevate prior or at the time of metastatic progression. Table S1. MMP-7, sFas and FasL serum levels at baseline and at time of radiographic progression.
Mmp ‐7 ; Fas ; Serum ; Prognosis ; Docetaxel ; #Pcsm ; #Prostatecancer