Purpose: Urokinase-plasminogen activator (uPA), its receptor (uPAR), and the plasmin-activator
inhibitor type 1 (PAI-1) have been associated with oncologic outcomes in various malignancies
and could help identify bladder cancer (BC) patients treated with radical cystectomy
(RC) who are likely to benefit from intensification of therapy to prevent disease
progression. Our aim was to assess the value of uPA, uPAR, and PAI-1 for prognosticating
survival outcomes of patients treated with RC for BC. Materials and methods: Tumor
specimens from 272 consecutive patients treated with RC for advanced BC were assessed
with immunohistochemical staining for uPA, uPAR, and PAI-1. Overexpression was assessed
by pathological image analysis. Kaplan-Meier estimates and multivariable Cox-regression
were used to analyze survival. Harrell's C-index was used to assess for clinical impact
of the uPA system. Results: uPA, uPAR, and PAI-1 were overexpressed in 48.2%, 51.1%,
and 52.2% of patients, respectively. uPA overexpression was associated with lymphovascular
invasion (P = 0.034) and nodal status (P = 0.013); PM-1 overexpression was associated
with primary muscle-invasive BC (P = 0.015) and lymphovascular invasion (P = 0.024).
uPA, uPAR, and the number of overexpressed markers were all 3 significantly associated
with shorter overall recurrence-free-, distant recurrence-free-, and cancer-specific
survival. In multivariable analyses, uPA overexpression remained associated with shorter
recurrence-free survival (hazard ratio [HR] = 1.79; P = 0.036) in the entire cohort,
in patients without lymph node metastasis (HR = 1.98; P = 0.018) and those with nonorgan-confined
disease (HR = 1.98; P = 0.022). uPAR overexpression was associated with shorter recurrence-free
survival in patients without lymph node metastasis (HR = 2.01; P = 0.021) and those
with organ-confined disease (HR = 4.11; P = 0.037). Conclusion: Members of the uPA
system are associated with features of biologically aggressive BC and oncologic outcomes.
However, their value beyond currently available information remains limited. (C) 2020
Elsevier Inc. All rights reserved.
