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

Abstract

PURPOSE:

We sought 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).

MATERIALS AND METHODS:

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.

RESULTS:

Preoperative plasma uPA, SuPAR and PAI-one levels were significantly elevated in patients harboring adverse pathological features. Higher levels of all biomarkers were independently associated with an increased risk of lymph node metastasis; uPA levels were also independently associated with ≥pT3 disease. Preoperative uPA and SuPAR were independently associated with recurrence-free and cancer-specific survival. The addition of these biomarkers to standard pre-treatment and post-treatment models improved the discriminatory power for prediction of lymph node metastasis, ≥pT3 disease, and recurrence-free and cancer-specific survival by a prognostically significant margin.

CONCLUSIONS:

We confirmed that elevated preoperative plasma levels of uPA, SuPAR and PAI-one 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.

• 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
• Journal: The Journal of urology (J Urol) Vol. 206 Issue 5 Pg. 1122-1131 (11 2021) ISSN: 1527-3792 [Electronic] United States
• PMID: 34181469 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• PLAUR protein, human
• Plasminogen Activator Inhibitor 1
• Receptors, Urokinase Plasminogen Activator
• SERPINE1 protein, human
• Urokinase-Type Plasminogen Activator

Topics

• Aged
• Biomarkers, Tumor (blood)
• Carcinoma, Transitional Cell (blood, diagnosis, mortality, surgery)
• Cystectomy
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Lymphatic Metastasis
• Male
• Neoplasm Recurrence, Local (epidemiology)
• Neoplasm Staging
• Plasminogen Activator Inhibitor 1 (blood)
• Preoperative Period
• Prognosis
• Receptors, Urokinase Plasminogen Activator (blood)
• Retrospective Studies
• Risk Assessment (statistics & numerical data)
• Urinary Bladder (pathology, surgery)
• Urinary Bladder Neoplasms (blood, diagnosis, mortality, surgery)
• Urokinase-Type Plasminogen Activator (blood)