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Prognostic value of urinary cytology and other biomarkers for recurrence and progression in bladder cancer: a prospective study

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Abstract

Purpose

Urinary cytology (C) and cystoscopy remain the gold standard for the detection and screening of bladder cancer (BC). In this prospective study, we analyzed whether baseline C, ImmunoCyt (I), BTA Stat (B), hemoglobin dipstick (H), and NMP22 BladderChek (N) can predict recurrence and progression.

Methods

Urinary samples from 91 patients with BC were prospectively collected over an 18-month period. Baseline characteristics of the population included patient demographics, various clinicopathological variables and use of intravesical therapy. Progression and recurrence were then assessed after a median follow-up of 48 months (IQR 23.7–59.5). Univariate and multivariate analyses were performed using COX proportional hazards models.

Results

On univariate analysis, C (HR 1.36; p = 0.26), I (HR 0.89; p = 0.66), B (HR 0.80; p = 0.42), H (HR 0.75; p = 0.30), and N (HR 0.82; p = 0.48) were not associated with recurrence-free survival (RFS). With regard to progression-free survival (PFS), C was significantly prognostic (HR 2.67; p = 0.017), whereas I, B, H, and N were not. On multivariable analysis, NMP22 was the only marker to be independently associated with RFS (HR 0.41, p < 0.01) and PFS (HR 0.32, p = 0.02).

Conclusion

Based on the results of this study, baseline C, B, I, and H were not independently prognostic. Prognostic impact of NMP22 requires further validation in a multicenter larger study.

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References

  1. Canadian Cancer Society’s Advisory Committee on Cancer Statistics (2014) Canadian cancer statistics 2014. Canadian Cancer Society, Toronto. ISSN 0835-2976

  2. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (1975–2011) SEER cancer statistics review, National Cancer Institute. Bethesda. http://seer.cancer.gov/csr/1975_2011/. Based on Nov 2013 SEER data submission, posted to the SEER web site, Apr 2014

  3. Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63:234–241

    Article  PubMed  Google Scholar 

  4. Rubben H, Lutzeyer W, Fischer N, Deutz F, Lagragne W, Giani G (1988) Natural history and treatment of low and high risk superficial bladder tumors. J Urol 139:283–285

    CAS  PubMed  Google Scholar 

  5. Heney NM, Ahmed S, Flanagan MJ, Frable W, Corder MP, Hafermann MD, Hawkins IR (1983) Superficial bladder cancer: progression and recurrence. J Urol 130:1083–1086

    CAS  PubMed  Google Scholar 

  6. Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Palou J, Algaba F, Vincent-Rodriguez J (2000) Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 164:680–684

    Article  CAS  PubMed  Google Scholar 

  7. Kassouf W, Kamat A, Zlotta A, Bochner BH, Moore R, So A, Izawa J, Rendon RA, Lacombe L, Aprikian AG (2010) Canadian guidelines for treatment of non-muscle invasive bladder cancer—a focus on intravesical therapy. Can Urol Assoc J 4(3):168–173

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hall CM, Chang SS, Dalbagni G, Pruthi RS, Seigne JD, Skinner EC, Wolf JS Jr, Schellhammer PF (2007) Guideline for the management of nonmuscle invasive bladder cancer: (stages Ta, T1 and Tis); update 2007. J Urol 178(6):2314–2330

    Article  PubMed  Google Scholar 

  9. Babjuk M, Bohle A, Burger M, Comperat E, Kaasinen E, Palou J, van Rhijn BWG, Roupret M, Shariat S, Sylvester R, Zigeuner R (2014) EAU guidelines on non-muscle-invasive bladder cancer (Ta, T1 and CIS); 2014. Eur Urol 65(3):778–792

    Google Scholar 

  10. Avritscher EB, Cooksley CD, Grossman HB, Sabichi AL, Hamblin L, Dinney CP, Elting LS (2006) Clinical model of lifetime cost of treating bladder cancer and associated complications. Urology 68:549–553

    Article  PubMed  Google Scholar 

  11. Yafi FA, Brimo F, Auger M, Aprkian A, Tanguay S, Kassouf W (2013) Is the performance of urinary cytology as high as reported historically? A contemporary analysis in the detection and surveillance of bladder cancer. Urol Oncol 32:e1–e6. doi:10.1016/j.urolonc.2012.09.011

    PubMed  Google Scholar 

  12. Lotan Y, Roehrborn CG (2003) Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses. Urology 61:109–118, discussion 118

  13. van Rhijn BW, van der Poel HG, van der Kwast TH (2005) Urine markers for bladder cancer surveillance: a systematic review. Eur Urol 47:736–748

    Article  PubMed  Google Scholar 

  14. Dey P (2004) Urinary markers of bladder carcinoma. Clin Chim Acta 340:57–65

    Article  CAS  PubMed  Google Scholar 

  15. Budman LI, Kassouf W, Steinberg JR (2008) Biomarkers for detection and surveillance of bladder cancer. Can Urol Assoc J 2:212–221

    PubMed  PubMed Central  Google Scholar 

  16. Yafi FA, Brimo F, Steinberg J, Aprikian AG, Tanguay S, Kassouf W (2014) Prospective analysis of sensitivity and specificity of urinary cytology and other urinary biomarkers for bladder cancer. Urol Oncol 33(2):66.e25–66.e31. doi:10.1016/j.urolonc.2014.06.008

    Article  Google Scholar 

  17. Brimo F, Vollmer RT, Case B, Aprikian A, Kassouf W, Auger M (2009) Accuracy of urine cytology and the significance of an atypical category. Am J Clin Pathol 132:785–793. doi:10.1309/AJCPPRZLG9KT9AXL

    Article  PubMed  Google Scholar 

  18. Lopez-Beltran A, Montironi R (2004) Non-invasive urothelial neoplasms: according to the most recent WHO classification. Eur Urol 46:170–176

    Article  PubMed  Google Scholar 

  19. Lau P, Chin JL, Pautler S, Razvi H, Izawa JI (2009) NMP22 is predictive of recurrence in high-risk superficial bladder cancer patients. CUAJ 3:454–458

    PubMed  PubMed Central  Google Scholar 

  20. Salama RH, Selem TH, El-Gammal M, Elhagagy AE, Bakar SM (2013) Urinary tumor markers could predict survival in bladder carcinoma. Indian J Clin Biochem 28:265–271. doi:10.1007/s12291-012-0266-z

    Article  CAS  PubMed  Google Scholar 

  21. Todenhofer T, Hennenlotter J, Guttenberg P, Mohrhardt S, Kuehs U, Esser M, Aufderklamm S, Bier S, Harland N, Rausch S, Gakis G, Stenzl A, Schwentner C (2015) Prognostic relevance of positive urine markers in patients with negative cystoscopy during surveillance of bladder cancer. BMC Cancer 15:155–165. doi:10.1186/s12885-015-1089-0

    Article  PubMed  PubMed Central  Google Scholar 

  22. Shahrokh SF, Savage C, Chromecki TF, Sun M, Scherr DS, Lee RK, Lughezzani G, Remzi M, Marberger MJ, Karakiewicz PI, Vickers AJ (2011) Assessing the clinical benefit of nuclear matrix protein 22 in the surveillance of patients with nonmuscle-invasive bladder cancer and negative cytology. Cancer 117:2892–2897. doi:10.1002/cncr.25903

    Article  Google Scholar 

  23. Joung JY, Park S, Yoon H, Kwon WA, Cho IC, Seo HK, Chung J, Hwang SH, Lee CW, Lee KH (2013) Overestimation of nuclear matrix protein 22 in concentrated urine. J Urol 82:1059–1064. doi:10.1016/j.urology.2013.05.056

    Article  Google Scholar 

  24. Miyake M, Goodison S, Giacoia EG, Rizwani W, Ross S, Rosser CJ (2012) Influencing factors on the NMP-22 urine assay: an experimental model. BMC Urol 12:23. doi:10.1186/1471-2490-12-23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Todenhofer T, Hennenlotter J, Kuhs U, Tews V, Gakis G, Aufderklamm S, Stenzl A, Schwentner C (2012) Influence of urinary tract instrumentation and inflammation on the performance of urine markers for the detection of bladder cancer. J Urol 79:620–624. doi:10.1016/j.urology.2011.10.067

    Article  Google Scholar 

  26. Todenhofer T, Hennenlotter J, Tews V, Gakis G, Aufderklamm S, Kuehs U, Stenzl A, Schwentner C (2013) Impact of different grades of microscopic hematuria on the performance of urine-based markers for the detection of urothelial carcinoma. Urol Oncol 31:1148–1154. doi:10.1016/j.urolonc.2011.10.011

    Article  PubMed  Google Scholar 

  27. Onal B, Unsal H, Yilmaz S, Koybasioglu F, Altug U (2014) The use of urinary nuclear matrix protein 22 (NMP22) as a diagnostic adjunct to urine cytology for monitoring of recurrent bladder cancer—institutional experience and review. Diagn Cytopahtol 43:307–314. doi:10.1002/dc.23239

    Article  Google Scholar 

  28. Kamat AM, Briggman J, Urbauer DL, Svatek R, Gonzalez GMN, Anderson R, Grossman HB, Prat F, Dinney CP (2015) Cytokine panel for response to intravesical therapy (CyPRIT): nomogram of changes in urinary cytokine levels predicts patient response to bacillus Calmette-Guerin. Eur Urol. doi:10.1016/j.eururo.2015.06.023

    Google Scholar 

  29. Kamat AM, Dickstein RJ, Messetti F, Anderson R, Pretzsch SM, Gonzalez GN, Katz RL, Khanna A, Zaidi T, Wu X, Grossman HB, Dinney CP (2012) Use of fluorescence in situ hybridization to predict patient response to BCG therapy for bladder cancer: results of a prospective trial. J Urol 187:862–867. doi:10.1016/j.juro.2011.10.144

    Article  PubMed  PubMed Central  Google Scholar 

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Authors’ contribution

M.D. Bell was involved in data collection and data analysis and wrote the manuscript. F.A. Yafi, F. Brimo, J. Steinberg, A.G. Aprikian, and S. Tanguay were involved in data collection. W. Kassouf was involved in project development and data collection and edited the manuscript.

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Authors and Affiliations

  1. Department of Surgery (Urology), McGill University, Montreal, QC, Canada

    Michael D. Bell, Faysal A. Yafi, Fadi Brimo, Jordan Steinberg, Armen G. Aprikian, Simon Tanguay & Wassim Kassouf

  2. Division of Pathology, McGill University Health Center, Montreal, QC, Canada

    Fadi Brimo

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  1. Michael D. Bell
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  2. Faysal A. Yafi
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Correspondence to Wassim Kassouf.

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The authors declare that they have no conflict of interest.

Informed consent

This study met the ethical standards of our internal review board, and informed consent was obtained from all patients prior to inclusion.

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Bell, M.D., Yafi, F.A., Brimo, F. et al. Prognostic value of urinary cytology and other biomarkers for recurrence and progression in bladder cancer: a prospective study. World J Urol 34, 1405–1409 (2016). https://doi.org/10.1007/s00345-016-1795-5

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  • DOI: https://doi.org/10.1007/s00345-016-1795-5

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