Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes After Radical Cystectomy.

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To validate the association of plasma-levels of urokinase-type plasminogen activator (uPA), its soluble receptor (SuPAR) and its inhibitor (PAI-One) with oncologic outcomes in a large cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).We collected preoperative blood samples from 1,036 consecutive patients treated with RC for UCB. Plasma specimens were assessed for levels of uPA, SuPAR and PAI-One. Retrospective logistic and Cox regression analyses were performed to assess their correlation with clinical outcomes. The additional clinical net-benefit provided by the biomarkers was evaluated using decision curve analysis (DCA).Preoperative plasma uPA, SuPAR and PAI-One levels were significantly elevated in patients harboring adverse pathologic features. Higher levels of all biomarkers were independently associated with an increased risk for lymph node metastasis (LNM); uPA levels were also independently associated with ≥pT3 disease. Preoperative uPA and SuPAR were independently associated with recurrence-free survival (RFS) and cancer-specific survival (CSS). The addition of these biomarkers to standard pre- and posttreatment models improved the discriminatory power for prediction of LNM, ≥pT3 disease, RFS and CSS by a prognostically significant margin.We confirmed that elevated preoperative plasma-levels of uPA, SuPAR and PAI-One levels are associated with features of aggressive disease and worse survival outcomes in patients treated with RC for UCB. These biomarkers hold potential in identifying patients who are likely to benefit from intensified/multimodal therapy. They also demonstrated the ability to improve the discriminatory power of predictive/prognostic models, thus refining personalized clinical decision making.

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Authors: Victor M Schuettfort, Benjamin Pradere, David D’Andrea, Nico C Grossmann, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Michael Rink, Pierre I Karakiewicz, Reza Sari Motlagh, Satoshi Katayama, Yair Lotan, Douglas Scherr, Mohammad Abufaraj, Harun Fajkovica, Eva Compérat, Dmitry Enikeev, Shahrokh F Shariat