Shoji Kimura1, Francesco Soria2, David D'Andrea3, Beat Foerster4, Mohammad Abufaraj5, Mihai D Vartolomei6, Pierre I Karakiewicz7, Romain Mathieu8, Marco Moschini9, Michael Rink10, Shin Egawa11, Shahrokh F Shariat12, Kilian M Gust13. 1. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan. 2. Department of Urology, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy. 3. Department of Urology, Medical University of Vienna, Vienna, Austria. 4. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Kantonsspital Winterthur, Winterthur, Switzerland. 5. Department of Urology, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan. 6. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Cell and Molecular Biology, University of Medicine and Pharmacy, Tirgu Mures, Romania. 7. Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada. 8. Department of Urology, Rennes University Hospital, Rennes, France. 9. Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland; Urological Research Institute, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. 10. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 11. Department of Urology, Jikei University School of Medicine, Tokyo, Japan. 12. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. 13. Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. Electronic address: Kilian.gust@meduniwien.ac.at.
Abstract
BACKGROUND: Serum cholinesterase (ChE) has been reported to be a prognostic factor in several cancers, but its relationship with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) has not yet been well-studied. MATERIALS AND METHODS: We retrospectively assessed 1117 patients with NMIBC undergoing transurethral resection of the bladder. Cox regression analyses were performed to elucidate the association between preoperative ChE and oncologic outcomes such as recurrence-free survival (RFS) and progression-free survival. RESULTS: The median preoperative ChE level was 5.51 kU/L (interquartile range, 4.95-7.01), and the optimal cut-off value of ChE obtained from receiver operator characteristic analysis was 5.55 kU/L. The 5-year RFS in patients with low and normal ChE levels were 41.1% and 70.0%, respectively (P < .001). The 5-year progression-free survival in patients with low and normal ChE levels were 93.2% and 91.4%, respectively (P = .053). On multivariable analysis, ChE was significantly associated with shorter RFS (P < .001). ChE as a continuous variable and low ChE levels improved the C-index for prediction of disease recurrence by 4.0% and 2.7% to 72.4% and 71.1%, respectively. In patients stratified into the European Association of Urology high-risk category, serum ChE was also a strong predictor of disease recurrence (hazard ratio, 4.14; 95% confidence interval, 2.90-5.89). Moreover, in the European Association of Urology high-risk patients treated with bacillus Calmette-Guérin immunotherapy, serum ChE was still strongly correlated with worse RFS (hazard ratio, 5.46; 95% confidence interval, 2.91-10.2). CONCLUSIONS: Decreased ChE is associated with shorter RFS in patients with NMIBC undergoing transurethral resection of the bladder. Preoperative ChE could improve patients' risk stratification and selection for adjuvant therapy. The mechanisms underlying this association needs further elucidation to design potential targets for intervention.
BACKGROUND: Serum cholinesterase (ChE) has been reported to be a prognostic factor in several cancers, but its relationship with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) has not yet been well-studied. MATERIALS AND METHODS: We retrospectively assessed 1117 patients with NMIBC undergoing transurethral resection of the bladder. Cox regression analyses were performed to elucidate the association between preoperative ChE and oncologic outcomes such as recurrence-free survival (RFS) and progression-free survival. RESULTS: The median preoperative ChE level was 5.51 kU/L (interquartile range, 4.95-7.01), and the optimal cut-off value of ChE obtained from receiver operator characteristic analysis was 5.55 kU/L. The 5-year RFS in patients with low and normal ChE levels were 41.1% and 70.0%, respectively (P < .001). The 5-year progression-free survival in patients with low and normal ChE levels were 93.2% and 91.4%, respectively (P = .053). On multivariable analysis, ChE was significantly associated with shorter RFS (P < .001). ChE as a continuous variable and low ChE levels improved the C-index for prediction of disease recurrence by 4.0% and 2.7% to 72.4% and 71.1%, respectively. In patients stratified into the European Association of Urology high-risk category, serum ChE was also a strong predictor of disease recurrence (hazard ratio, 4.14; 95% confidence interval, 2.90-5.89). Moreover, in the European Association of Urology high-risk patients treated with bacillus Calmette-Guérin immunotherapy, serum ChE was still strongly correlated with worse RFS (hazard ratio, 5.46; 95% confidence interval, 2.91-10.2). CONCLUSIONS: Decreased ChE is associated with shorter RFS in patients with NMIBC undergoing transurethral resection of the bladder. Preoperative ChE could improve patients' risk stratification and selection for adjuvant therapy. The mechanisms underlying this association needs further elucidation to design potential targets for intervention.
Authors: Mihaela Georgiana Musat; Christina Soeun Kwon; Elizabeth Masters; Slaven Sikirica; Debduth B Pijush; Anna Forsythe Journal: Clinicoecon Outcomes Res Date: 2022-01-10