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

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 -