To assess the role of the urokinase plasminogen activator (uPA) system as a prognostic biomarker in patients with nonmuscle invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB) with or without adjuvant intravesical therapy.

We stained TURB tissue from 827 NMIBC patients with uPA, its receptor (uPAR) and its inhibitor (PAI-1). The status of these markers was categorized as normal vs. overexpressed using the cutoffs of 30% for uPA, 50% for uPAR, and 30% for PAI-1. Multivariable Cox regression analyses were performed to evaluate the prognostic value of these markers.

uPA was overexpressed in 37.7% of patients, uPAR in 44.7% and PAI-1 in 44.6%. Overexpression of these markers was associated with high tumor grade. Within a median follow-up was 60 months (interquartile range: 22-109), uPA (hazard ratio [HR]: 1.40; P = 0.006), uPAR (HR: 1.70; P < 0.001), PAI-1 (HR: 1.35; P = 0.014), and the combination of all 3 markers (HR: 3.38; P < 0.001) were associated with recurrence-free survival (RFS); uPA (HR: 1.68; P = 0.035) and the combination of all 3 markers (HR: 8.79; P = 0.005) were associated with progression-free survival (PFS). The addition of the uPA system to a base model improved the discrimination by 1.3% for RFS and 2.1% for PFS. In subgroup analyses, uPA (HR: 2.19; P = 0.018) was associated with PFS in T1G3 patients and its addition to a base model improved the discrimination by 2.5%. uPA (HR: 1.44; P = 0.019), uPAR (HR: 1.54; P = 0.006), PAI-1 (HR: 1.46; P = 0.013) and the combination of all 3 markers (HR: 3.48; P < 0.001) were associated with RFS in TaG1-2 patients and their addition to a base model improved the discrimination by 2.1%.

uPA, uPAR, and PAI-1 are overexpressed in one-third to half of patients with NMIBC. Their overexpression is an independent prognosticator of RFS and PFS which improved the predictive accuracy of current clinicopathological characteristics. Biomarkers that capture the biological and clinical behavior of individual tumors may help personalize clinical decision-making in patients with NMIBC.

Urologic oncology. 2019 Jun 26 [Epub ahead of print]

Takehiro Iwata, Shoji Kimura, Mohammad Abufaraj, Florian Janisch, Mehdi Kardoust Parizi, Andrea Haitel, Micheal Rink, Morgan Rouprêt, Harun Fajkovic, Veronica Seebacher, Peter Nyirady, Pierre I Karakiewicz, Dmitry Enikeev, Leonid M Rapoport, Yasutomo Nasu, Shahrokh F Shariat

Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan., Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan., Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Teheran, Iran., Department of Pathology, Medical University of Vienna, Vienna, Austria., Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, Sorbonne Université, Paris, France., Department of Urology, Medical University of Vienna, Vienna, Austria., Department for Gynaecology and Gynaecologic Oncology, Medical University of Vienna, Vienna, Austria., Department of Urology, Semmelweis University, Budapest, Hungary., Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada., Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., Department of Urology, Weill Cornell Medical College, New York, NY., Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan., Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. Electronic address: .

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