Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes after Radical Cystectomy
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Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes after Radical Cystectomy. / Schuettfort, Victor M; Pradere, Benjamin; D'Andrea, David; Grossmann, Nico C; Quhal, Fahad; Mostafaei, Hadi; Laukhtina, Ekaterina; Mori, Keiichiro; Rink, Michael; Karakiewicz, Pierre I; Motlagh, Reza Sari; Katayama, Satoshi; Lotan, Yair; Scherr, Douglas; Abufaraj, Mohammad; Fajkovica, Harun; Compérat, Eva; Enikeev, Dmitry; Shariat, Shahrokh F.
In: J UROLOGY, Vol. 206, No. 5, 11.2021, p. 1122-1131.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes after Radical Cystectomy
AU - Schuettfort, Victor M
AU - Pradere, Benjamin
AU - D'Andrea, David
AU - Grossmann, Nico C
AU - Quhal, Fahad
AU - Mostafaei, Hadi
AU - Laukhtina, Ekaterina
AU - Mori, Keiichiro
AU - Rink, Michael
AU - Karakiewicz, Pierre I
AU - Motlagh, Reza Sari
AU - Katayama, Satoshi
AU - Lotan, Yair
AU - Scherr, Douglas
AU - Abufaraj, Mohammad
AU - Fajkovica, Harun
AU - Compérat, Eva
AU - Enikeev, Dmitry
AU - Shariat, Shahrokh F
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Aged
KW - Biomarkers, Tumor/blood
KW - Carcinoma, Transitional Cell/blood
KW - Cystectomy
KW - Disease-Free Survival
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Lymphatic Metastasis
KW - Male
KW - Neoplasm Recurrence, Local/epidemiology
KW - Neoplasm Staging
KW - Plasminogen Activator Inhibitor 1/blood
KW - Preoperative Period
KW - Prognosis
KW - Receptors, Urokinase Plasminogen Activator/blood
KW - Retrospective Studies
KW - Risk Assessment/statistics & numerical data
KW - Urinary Bladder/pathology
KW - Urinary Bladder Neoplasms/blood
KW - Urokinase-Type Plasminogen Activator/blood
U2 - 10.1097/JU.0000000000001936
DO - 10.1097/JU.0000000000001936
M3 - SCORING: Journal article
C2 - 34181469
VL - 206
SP - 1122
EP - 1131
JO - J UROLOGY
JF - J UROLOGY
SN - 0022-5347
IS - 5
ER -