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Prognostic Value of Serum Cholinesterase in Non–muscle-invasive Bladder Cancer

      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.

      Keywords

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      References

        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2018.
        CA Cancer J Clin. 2018; 68: 7-30
        • Burger M.
        • Catto J.W.
        • Dalbagni G.
        • et al.
        Epidemiology and risk factors of urothelial bladder cancer.
        Eur Urol. 2013; 63: 234-241
        • Kamat A.M.
        • Hegarty P.K.
        • Gee J.R.
        • et al.
        ICUD-EAU International Consultation on Bladder Cancer 2012: Screening, diagnosis, and molecular markers.
        Eur Urol. 2013; 63: 4-15
        • Soria F.
        • Moschini M.
        • Abufaraj M.
        • et al.
        Preoperative anemia is associated with disease recurrence and progression in patients with non-muscle-invasive bladder cancer.
        Urol Oncol. 2017; 35: 113.e9-113.e14
        • Babjuk M.
        • Bohle A.
        • Burger M.
        • et al.
        EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016.
        Eur Urol. 2017; 71: 447-461
        • Spiess P.E.
        • Agarwal N.
        • Bangs R.
        • et al.
        Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.
        J Natl Compr Canc Netw. 2017; 15: 1240-1267
        • Alfred Witjes J.
        • Lebret T.
        • Compérat E.M.
        • et al.
        Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer.
        Eur Urol. 2017; 71: 462-475
        • Moschini M.
        • Sharma V.
        • Dell'oglio P.
        • et al.
        Comparing long-term outcomes of primary and progressive carcinoma invading bladder muscle after radical cystectomy.
        BJU Int. 2016; 117: 604-610
        • Fajkovic H.
        • Halpern J.A.
        • Cha E.K.
        • et al.
        Impact of gender on bladder cancer incidence, staging, and prognosis.
        World J Urol. 2011; 29: 457-463
        • Rieken M.
        • Shariat S.F.
        • Kluth L.
        • et al.
        Comparison of the EORTC tables and the EAU categories for risk stratification of patients with nonmuscle-invasive bladder cancer.
        Urol Oncol. 2018; 36: 8.e17-8.e24
        • Karakiewicz P.I.
        • Shariat S.F.
        • Palapattu G.S.
        • et al.
        Precystectomy nomogram for prediction of advanced bladder cancer stage.
        Eur Urol. 2006; 50 ([discussion: 1261-1262]): 1254-1260
        • Nielsen M.E.
        • Shariat S.F.
        • Karakiewicz P.I.
        • et al.
        Advanced age is associated with poorer bladder cancer-specific survival in patients treated with radical cystectomy.
        Eur Urol. 2007; 51 ([discussion: 698-706]): 699-706
        • Shariat S.F.
        • Chade D.C.
        • Karakiewicz P.I.
        • et al.
        Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer.
        J Urol. 2010; 183: 68-75
        • Shariat S.F.
        • Zlotta A.R.
        • Ashfaq R.
        • Sagalowsky A.I.
        • Lotan Y.
        Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness.
        Mod Pathol. 2007; 20: 445-459
        • Byrne R.R.
        • Shariat S.F.
        • Brown R.
        • et al.
        E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup.
        J Urol. 2001; 165: 1473-1479
        • Margulis V.
        • Shariat S.F.
        • Ashfaq R.
        • Sagalowsky A.I.
        • Lotan Y.
        Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease.
        Clin Cancer Res. 2006; 12: 7369-7373
        • Shariat S.F.
        • Ashfaq R.
        • Karakiewicz P.I.
        • Saeedi O.
        • Sagalowsky A.I.
        • Lotan Y.
        Survivin expression is associated with bladder cancer presence, stage, progression, and mortality.
        Cancer. 2007; 109: 1106-1113
        • Mitsunaga S.
        • Kinoshita T.
        • Hasebe T.
        • et al.
        Low serum level of cholinesterase at recurrence of pancreatic cancer is a poor prognostic factor and relates to systemic disorder and nerve plexus invasion.
        Pancreas. 2008; 36: 241-248
        • Lampon N.
        • Hermida-Cadahia E.F.
        • Riveiro A.
        • Tutor J.C.
        Association between butyrylcholinesterase activity and low-grade systemic inflammation.
        Ann Hepatol. 2012; 11: 356-363
        • Kumar R.
        • Razab S.
        • Prabhu K.
        • Ray S.
        • Prakash B.
        Serum butyrylcholinesterase and zinc in breast cancer.
        J Cancer Res Ther. 2017; 13: 367-370
        • Santarpia L.
        • Grandone I.
        • Contaldo F.
        • Pasanisi F.
        Butyrylcholinesterase as a prognostic marker: a review of the literature.
        J Cachexia Sarcopenia Muscle. 2013; 4: 31-39
        • Koie T.
        • Ohyama C.
        • Yamamoto H.
        • et al.
        Significance of preoperative butyrylcholinesterase as an independent predictor of survival in patients with muscle-invasive bladder cancer treated with radical cystectomy.
        Urol Oncol. 2014; 32: 820-825
        • Youden W.J.
        Index for rating diagnostic tests.
        Cancer. 1950; 3: 32-35
        • Popescu T.A.
        • Fekete T.
        • Popescu E.
        • Bojthy I.
        • Laszlo M.
        Serum pseudocholinesterase activity during experimental fattening.
        Med Interne. 1976; 14: 71-73
        • Vallianou N.G.
        • Evangelopoulos A.A.
        • Bountziouka V.
        • et al.
        Association of butyrylcholinesterase with cardiometabolic risk factors among apparently healthy adults.
        J Cardiovasc Med (Hagerstown). 2014; 15: 377-383
        • Camarero Gonzalez E.
        • Munoz Leira V.
        • Iglesias Guerrero M.
        • Fernandez Alvarez J.A.
        • Cabezas-Cerrato J.
        [Protein-energy malnutrition: its effects on 4 metabolic parameters].
        Nutr Hosp. 1995; 10: 158-160
        • Coulter D.W.
        • Boettner A.D.
        • Kortylewicz Z.P.
        • et al.
        Butyrylcholinesterase as a blood biomarker in neuroblastoma.
        J Pediatr Hematol Oncol. 2017; 39: 272-281
        • Prabhu K.
        • Naik D.
        • Ray S.
        • Vadiraj
        • Rao A.
        • Kamath A.
        Significance of serum butyrylcholinesterase levels in oral cancer.
        Australas Med J. 2011; 4: 374-378
        • Battisti V.
        • Bagatini M.D.
        • Maders L.D.
        • et al.
        Cholinesterase activities and biochemical determinations in patients with prostate cancer: influence of Gleason score, treatment and bone metastasis.
        Biomed Pharmacother. 2012; 66: 249-255
        • Noro D.
        • Koie T.
        • Hashimoto Y.
        • et al.
        Significance of preoperative butyrylcholinesterase level as an independent predictor of survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy.
        Jpn J Clin Oncol. 2018; 48: 184-189
        • Sylvester R.J.
        • van der Meijden A.P.
        • Oosterlinck W.
        • et al.
        Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials.
        Eur Urol. 2006; 49 ([discussion: 475-477]): 466-475
        • Xylinas E.
        • Kent M.
        • Kluth L.
        • et al.
        Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder.
        Br J Cancer. 2013; 109: 1460-1466
        • Fritsche H.M.
        • Burger M.
        • Svatek R.S.
        • et al.
        Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort.
        Eur Urol. 2010; 57: 300-309
        • Shariat S.F.
        • Ashfaq R.
        • Sagalowsky A.I.
        • Lotan Y.
        Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis.
        Hum Pathol. 2006; 37: 1568-1576
        • Shariat S.F.
        • Kim J.
        • Raptidis G.
        • Ayala G.E.
        • Lerner S.P.
        Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder.
        Urology. 2003; 61: 1140-1145
        • Bensalah K.
        • Montorsi F.
        • Shariat S.F.
        Challenges of cancer biomarker profiling.
        Eur Urol. 2007; 52: 1601-1609