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Prognostic Role of the Urokinase Plasminogen Activator (Upa) System in Patients With Nonmuscle Invasive Bladder Cancer Publisher Pubmed



Iwata T1, 2 ; Kimura S1, 3 ; Abufaraj M1, 4 ; Janisch F1, 5 ; Parizi MK1, 6 ; Haitel A7 ; Rink M5 ; Roupret M8 ; Fajkovic H1 ; Seebacher V9 ; Nyirady P10 ; Karakiewicz PI11 ; Enikeev D12 ; Rapoport LM13 Show All Authors
Authors
  1. Iwata T1, 2
  2. Kimura S1, 3
  3. Abufaraj M1, 4
  4. Janisch F1, 5
  5. Parizi MK1, 6
  6. Haitel A7
  7. Rink M5
  8. Roupret M8
  9. Fajkovic H1
  10. Seebacher V9
  11. Nyirady P10
  12. Karakiewicz PI11
  13. Enikeev D12
  14. Rapoport LM13
  15. Nasu Y2
  16. Shariat SF1, 12, 13, 14, 15
Show Affiliations
Authors Affiliations
  1. 1. Department of Urology, Medical University of Vienna, Vienna, Austria
  2. 2. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  3. 3. Department of Urology, Jikei University School of Medicine, Tokyo, Japan
  4. 4. Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan
  5. 5. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  6. 6. Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Teheran, Iran
  7. 7. Department of Pathology, Medical University of Vienna, Vienna, Austria
  8. 8. Department of Urology, Sorbonne Universite, Paris, France
  9. 9. Department for Gynaecology and Gynaecologic Oncology, Medical University of Vienna, Vienna, Austria
  10. 10. Department of Urology, Semmelweis University, Budapest, Hungary
  11. 11. Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada
  12. 12. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russian Federation
  13. 13. Department of Urology, Weill Cornell Medical College, New York, NY, United States
  14. 14. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States
  15. 15. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria

Source: Urologic Oncology: Seminars and Original Investigations Published:2019


Abstract

Objectives: 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. Material and methods: 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. Results: 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%. Conclusion: 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. © 2019 Elsevier Inc.