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Molecular Prognostication in Bladder Cancer

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Genitourinary Cancers

Part of the book series: Cancer Treatment and Research ((CTAR,volume 175))

Abstract

Clinical outcomes for patients with bladder cancer have largely remained unchanged over the last three decades despite improvements in surgical techniques, perioperative therapies, and postoperative management. Current management still heavily relies on pathologic staging that does not always reflect an individual patient’s risk. The genesis and progression of bladder cancer is now increasingly recognized as being a result of alterations in several pathways that affect the cell cycle, apoptosis, cellular signaling, gene regulation, immune modulation, angiogenesis, and tumor cell invasion. Multiplexed assessment of biomarkers associated with alterations in these pathways offers novel insights into tumor behavior while identifying panels that are capable of reproducibly predicting patient outcomes. Future management of bladder cancer will likely incorporate such prognostic molecular models for risk stratification and treatment personalization.

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References

  1. Daneshmand S, Patel S, Lotan Y et al (2018) Efficacy and safety of blue light flexible cystoscopy with hexaminolevulinate (HAL) in the surveillance of bladder cancer: a phase III, comparative, multi-center study. J Urol 199:1158

    Google Scholar 

  2. Zlatev DV, Altobelli E, Liao JC (2015) Advances in imaging technologies in the evaluation of high-grade bladder cancer. Urol Clin North Am 42:147

    Article  PubMed  PubMed Central  Google Scholar 

  3. Birkhahn M, Mitra AP, Williams AJ et al (2013) A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine. Eur J Cancer 49:3159

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mitra AP, Cote RJ (2010) Molecular screening for bladder cancer: progress and potential. Nat Rev Urol 7:11

    Article  CAS  PubMed  Google Scholar 

  5. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2005) Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data. Eur Urol 48:202

    Article  Google Scholar 

  6. Daneshmand S, Ahmadi H, Schuckman AK et al (2014) Enhanced recovery protocol after radical cystectomy for bladder cancer. J Urol 192:50

    Article  PubMed  Google Scholar 

  7. Zehnder P, Studer UE, Skinner EC et al (2013) Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades. BJU Int 112:E51

    Article  PubMed  Google Scholar 

  8. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7

    Article  PubMed  Google Scholar 

  9. Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87

    Article  PubMed  Google Scholar 

  10. Mitra AP, Bartsch G, Cote RJ (2018) Risk factors and molecular features associated with bladder cancer development. In: Hansel DE, Lerner SP (eds) Precision molecular pathology of bladder cancer. Springer Nature, Cham, Switzerland, pp 3–28

    Chapter  Google Scholar 

  11. Mitra AP (2016) Molecular substratification of bladder cancer: moving towards individualized patient management. Ther Adv Urol 8:215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mitra AP, JordĂ  M, Cote RJ (2012) Pathological possibilities and pitfalls in detecting aggressive bladder cancer. Curr Opin Urol 22:397

    Article  PubMed  Google Scholar 

  13. Zehnder P, Moltzahn F, Daneshmand S et al (2014) Outcome in patients with exclusive carcinoma in situ (CIS) after radical cystectomy. BJU Int 113:65

    Article  PubMed  Google Scholar 

  14. Wu XR (2005) Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer 5:713

    Article  CAS  PubMed  Google Scholar 

  15. Knowles MA (2006) Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis 27:361

    Article  CAS  PubMed  Google Scholar 

  16. Rieger-Christ KM, Mourtzinos A, Lee PJ et al (2003) Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection. Cancer 98:737

    Article  CAS  PubMed  Google Scholar 

  17. van Rhijn BW, van der Kwast TH, Vis AN et al (2004) FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma. Cancer Res 64:1911

    Article  PubMed  Google Scholar 

  18. Bakkar AA, Wallerand H, Radvanyi F et al (2003) FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder. Cancer Res 63:8108

    CAS  PubMed  Google Scholar 

  19. Orlow I, LaRue H, Osman I et al (1999) Deletions of the INK4A gene in superficial bladder tumors. Association with recurrence. Am J Pathol 155:105

    CAS  PubMed  Google Scholar 

  20. Mitra AP, Datar RH, Cote RJ (2006) Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification. J Clin Oncol 24:5552

    Article  CAS  PubMed  Google Scholar 

  21. Spruck CH III, Ohneseit PF, Gonzalez-Zulueta M et al (1994) Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 54:784

    CAS  PubMed  Google Scholar 

  22. Hartmann A, Schlake G, Zaak D et al (2002) Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder. Cancer Res 62:809

    CAS  PubMed  Google Scholar 

  23. Korkolopoulou P, Christodoulou P, Lazaris A et al (2001) Prognostic implications of aberrations in p16/pRb pathway in urothelial bladder carcinomas: a multivariate analysis including p53 expression and proliferation markers. Eur Urol 39:167

    Article  CAS  PubMed  Google Scholar 

  24. Mitra AP, Quinn DI, Dorff TB et al (2012) Factors influencing post-recurrence survival in bladder cancer following radical cystectomy. BJU Int 109:846

    Article  PubMed  Google Scholar 

  25. The Cancer Genome Atlas Research Network (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507:315

    Google Scholar 

  26. Nordentoft I, Lamy P, Birkenkamp-Demtröder K et al (2014) Mutational context and diverse clonal development in early and late bladder cancer. Cell Rep 7:1649

    Article  CAS  PubMed  Google Scholar 

  27. Mitra AP, Cote RJ (2009) Molecular pathogenesis and diagnostics of bladder cancer. Annu Rev Pathol 4:251

    Article  CAS  PubMed  Google Scholar 

  28. Mitra AP, Cote RJ (2007) Searching for novel therapeutics and targets: insights from clinical trials. Urol Oncol 25:341

    Article  CAS  PubMed  Google Scholar 

  29. Youssef RF, Mitra AP, Bartsch G Jr et al (2009) Molecular targets and targeted therapies in bladder cancer management. World J Urol 27:9

    Article  PubMed  Google Scholar 

  30. Mitra AP, Hansel DE, Cote RJ (2012) Prognostic value of cell-cycle regulation biomarkers in bladder cancer. Semin Oncol 39:524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mitra AP, Birkhahn M, Cote RJ (2007) p53 and retinoblastoma pathways in bladder cancer. World J Urol 25:563

    Article  CAS  PubMed  Google Scholar 

  32. Mitra AP, Datar RH, Cote RJ (2005) Molecular staging of bladder cancer. BJU Int 96:7

    Article  CAS  PubMed  Google Scholar 

  33. Mitra AP, Lin H, Cote RJ et al (2005) Biomarker profiling for cancer diagnosis, prognosis and therapeutic management. Natl Med J India 18:304

    PubMed  Google Scholar 

  34. Esrig D, Elmajian D, Groshen S et al (1994) Accumulation of nuclear p53 and tumor progression in bladder cancer. N Engl J Med 331:1259

    Article  CAS  PubMed  Google Scholar 

  35. Sarkis AS, Dalbagni G, Cordon-Cardo C et al (1993) Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J Natl Cancer Inst 85:53

    Article  CAS  PubMed  Google Scholar 

  36. Serth J, Kuczyk MA, Bokemeyer C et al (1995) p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder. Br J Cancer 71:201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chatterjee SJ, Datar R, Youssefzadeh D et al (2004) Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma. J Clin Oncol 22:1007

    Article  CAS  PubMed  Google Scholar 

  38. Shariat SF, Tokunaga H, Zhou J et al (2004) p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer. J Clin Oncol 22:1014

    Article  CAS  PubMed  Google Scholar 

  39. Shariat SF, Lotan Y, Karakiewicz PI et al (2009) p53 predictive value for pT1-2 N0 disease at radical cystectomy. J Urol 182:907

    Article  PubMed  Google Scholar 

  40. Shariat SF, Zlotta AR, Ashfaq R et al (2007) Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness. Mod Pathol 20:445

    Article  CAS  PubMed  Google Scholar 

  41. Shariat SF, Bolenz C, Karakiewicz PI et al (2010) p53 expression in patients with advanced urothelial cancer of the urinary bladder. BJU Int 105:489

    Article  PubMed  Google Scholar 

  42. Shariat SF, Chade DC, Karakiewicz PI et al (2010) Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J Urol 183:68

    Article  PubMed  Google Scholar 

  43. George B, Datar RH, Wu L et al (2007) p53 gene and protein status: The role of p53 alterations in predicting outcome in patients with bladder cancer. J Clin Oncol 25:5352

    Article  CAS  PubMed  Google Scholar 

  44. Malats N, Bustos A, Nascimento CM et al (2005) P53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol 6:678

    Article  CAS  PubMed  Google Scholar 

  45. Stadler WM, Lerner SP, Groshen S et al (2011) Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol 29:3443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Stein JP, Ginsberg DA, Grossfeld GD et al (1998) Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer. J Natl Cancer Inst 90:1072

    Article  CAS  PubMed  Google Scholar 

  47. Simon R, Struckmann K, Schraml P et al (2002) Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer. Oncogene 21:2476

    Article  CAS  PubMed  Google Scholar 

  48. Bates S, Phillips AC, Clark PA et al (1998) p14ARF links the tumour suppressors RB and p53. Nature 395:124

    Article  CAS  PubMed  Google Scholar 

  49. Rebouissou S, Herault A, Letouze E et al (2012) CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma. J Pathol 227:315

    Article  CAS  PubMed  Google Scholar 

  50. Miyamoto H, Shuin T, Torigoe S et al (1995) Retinoblastoma gene mutations in primary human bladder cancer. Br J Cancer 71:831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kapur P, Lotan Y, King E et al (2011) Primary adenocarcinoma of the urinary bladder: value of cell cycle biomarkers. Am J Clin Pathol 135:822

    Article  CAS  PubMed  Google Scholar 

  52. Kamai T, Takagi K, Asami H et al (2001) Decreasing of p27Kip1 and cyclin E protein levels is associated with progression from superficial into invasive bladder cancer. Br J Cancer 84:1242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Shariat SF, Bolenz C, Godoy G et al (2009) Predictive value of combined immunohistochemical markers in patients with pT1 urothelial carcinoma at radical cystectomy. J Urol 182:78

    Article  PubMed  Google Scholar 

  54. Shariat SF, Karakiewicz PI, Ashfaq R et al (2008) Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy. Cancer 112:315

    Article  PubMed  Google Scholar 

  55. Shariat SF, Chromecki TF, Cha EK et al (2012) Risk stratification of organ confined bladder cancer after radical cystectomy using cell cycle related biomarkers. J Urol 187:457

    Article  PubMed  Google Scholar 

  56. Koga S, Hirohata S, Kondo Y et al (2000) A novel telomerase-specific gene therapy: gene transfer of caspase-8 utilizing the human telomerase catalytic subunit gene promoter. Hum Gene Ther 11:1397

    Article  CAS  PubMed  Google Scholar 

  57. Karam JA, Lotan Y, Karakiewicz PI et al (2007) Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol 8:128

    Article  CAS  PubMed  Google Scholar 

  58. Shariat SF, Ashfaq R, Karakiewicz PI et al (2007) Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer 109:1106

    Article  CAS  PubMed  Google Scholar 

  59. Shariat SF, Karakiewicz PI, Godoy G et al (2009) Survivin as a prognostic marker for urothelial carcinoma of the bladder: a multicenter external validation study. Clin Cancer Res 15:7012

    Article  CAS  PubMed  Google Scholar 

  60. Ong F, Moonen LM, Gallee MP et al (2001) Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53. Radiother Oncol 61:169

    Article  CAS  PubMed  Google Scholar 

  61. Hussain SA, Ganesan R, Hiller L et al (2003) BCL2 expression predicts survival in patients receiving synchronous chemoradiotherapy in advanced transitional cell carcinoma of the bladder. Oncol Rep 10:571

    CAS  PubMed  Google Scholar 

  62. Cooke PW, James ND, Ganesan R et al (2000) Bcl-2 expression identifies patients with advanced bladder cancer treated by radiotherapy who benefit from neoadjuvant chemotherapy. BJU Int 85:829

    Article  CAS  PubMed  Google Scholar 

  63. Kong G, Shin KY, Oh YH et al (1998) Bcl-2 and p53 expressions in invasive bladder cancers. Acta Oncol 37:715

    Article  CAS  PubMed  Google Scholar 

  64. Wolf HK, Stober C, Hohenfellner R et al (2001) Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas. Tumour Biol 22:328

    Article  CAS  PubMed  Google Scholar 

  65. Gonzalez-Campora R, Davalos-Casanova G, Beato-Moreno A et al (2007) BCL-2, TP53 and BAX protein expression in superficial urothelial bladder carcinoma. Cancer Lett 250:292

    Article  CAS  PubMed  Google Scholar 

  66. Maluf FC, Cordon-Cardo C, Verbel DA et al (2006) Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment. Ann Oncol 17:1677

    Article  CAS  PubMed  Google Scholar 

  67. Giannopoulou I, Nakopoulou L, Zervas A et al (2002) Immunohistochemical study of pro-apoptotic factors Bax, Fas and CPP32 in urinary bladder cancer: prognostic implications. Urol Res 30:342

    Article  CAS  PubMed  Google Scholar 

  68. Korkolopoulou P, Lazaris A, Konstantinidou AE et al (2002) Differential expression of bcl-2 family proteins in bladder carcinomas. Relationship with apoptotic rate and survival. Eur Urol 41:274

    Article  CAS  PubMed  Google Scholar 

  69. Mitra AP, Lin H, Datar RH et al (2006) Molecular biology of bladder cancer: prognostic and clinical implications. Clin Genitourin Cancer 5:67

    Article  CAS  PubMed  Google Scholar 

  70. Mitra AP, Castelao JE, Hawes D et al (2013) Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program. Cancer 119:756

    Article  CAS  PubMed  Google Scholar 

  71. Pasin E, Josephson DY, Mitra AP et al (2008) Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Rev Urol 10:31

    PubMed  PubMed Central  Google Scholar 

  72. van Rhijn BW, Zuiverloon TC, Vis AN et al (2010) Molecular grade (FGFR3/MIB-1) and EORTC risk scores are predictive in primary non-muscle-invasive bladder cancer. Eur Urol 58:433

    Article  PubMed  Google Scholar 

  73. Jebar AH, Hurst CD, Tomlinson DC et al (2005) FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene 24:5218

    Article  CAS  PubMed  Google Scholar 

  74. Birkhahn M, Mitra AP, Williams AJ et al (2010) Predicting recurrence and progression of noninvasive papillary bladder cancer at initial presentation based on quantitative gene expression profiles. Eur Urol 57:12

    Article  CAS  PubMed  Google Scholar 

  75. Wright C, Mellon K, Johnston P et al (1991) Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Br J Cancer 63:967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Korkolopoulou P, Christodoulou P, Kapralos P et al (1997) The role of p53, MDM2 and c-erb B-2 oncoproteins, epidermal growth factor receptor and proliferation markers in the prognosis of urinary bladder cancer. Pathol Res Pract 193:767

    Article  CAS  PubMed  Google Scholar 

  77. Mellon JK, Lunec J, Wright C et al (1996) c-erbB-2 in bladder cancer: Molecular biology, correlation with epidermal growth factor receptors and prognostic value. J Urol 155:321

    Article  CAS  PubMed  Google Scholar 

  78. Liukkonen T, Rajala P, Raitanen M et al (1999) Prognostic value of MIB-1 score, p53, EGFr, mitotic index and papillary status in primary superficial (Stage pTa/T1) bladder cancer: a prospective comparative study. Eur Urol 36:393

    Article  CAS  PubMed  Google Scholar 

  79. Kramer C, Klasmeyer K, Bojar H et al (2007) Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB1 expression in bladder cancer and their relation to clinical outcome. Cancer 109:2016

    Article  CAS  PubMed  Google Scholar 

  80. Lipponen P, Eskelinen M (1994) Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis. Br J Cancer 69:1120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kruger S, Weitsch G, Buttner H et al (2002) Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome. Int J Oncol 21:981

    PubMed  Google Scholar 

  82. Kruger S, Weitsch G, Buttner H et al (2002) HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. Int J Cancer 102:514

    Article  CAS  PubMed  Google Scholar 

  83. Bolenz C, Shariat SF, Karakiewicz PI et al (2010) Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int 106:1216

    Article  PubMed  Google Scholar 

  84. Kassouf W, Black PC, Tuziak T et al (2008) Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer. J Urol 179:353

    Article  PubMed  Google Scholar 

  85. Jimenez RE, Hussain M, Bianco FJ Jr et al (2001) Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clin Cancer Res 7:2440

    CAS  PubMed  Google Scholar 

  86. Chow NH, Chan SH, Tzai TS et al (2001) Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clin Cancer Res 7:1957

    CAS  PubMed  Google Scholar 

  87. Memon AA, Sorensen BS, Meldgaard P et al (2006) The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients. Br J Cancer 94:1703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mitra AP, Skinner EC, Schuckman AK et al (2014) Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients. Urol Oncol 32:52.e1

    Article  Google Scholar 

  89. Tuygun C, Kankaya D, Imamoglu A et al (2011) Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression. Urol Oncol 29:43

    Article  CAS  PubMed  Google Scholar 

  90. Ide H, Inoue S, Miyamoto H (2017) Histopathological and prognostic significance of the expression of sex hormone receptors in bladder cancer: a meta-analysis of immunohistochemical studies. PLoS ONE 12:e0174746

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Boorjian S, Ugras S, Mongan NP et al (2004) Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64:383

    Article  PubMed  Google Scholar 

  92. Mir C, Shariat SF, van der Kwast TH et al (2011) Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study. BJU Int 108:24

    Article  PubMed  Google Scholar 

  93. Stephanou A, Brar BK, Knight RA et al (2000) Opposing actions of STAT-1 and STAT-3 on the Bcl-2 and Bcl-x promoters. Cell Death Differ 7:329

    Article  CAS  PubMed  Google Scholar 

  94. Mitra AP, Pagliarulo V, Yang D et al (2009) Generation of a concise gene panel for outcome prediction in urinary bladder cancer. J Clin Oncol 27:3929

    Article  PubMed  PubMed Central  Google Scholar 

  95. Choudhury A, Nelson LD, Teo MT et al (2010) MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res 70:7017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Laurberg JR, Brems-Eskildsen AS, Nordentoft I et al (2012) Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int 110:E1228

    Article  CAS  PubMed  Google Scholar 

  97. Martin RM, Kerr M, Teo MT et al (2014) Post-transcriptional regulation of MRE11 expression in muscle-invasive bladder tumours. Oncotarget 5:993

    Article  PubMed  PubMed Central  Google Scholar 

  98. Teo MT, Dyrskjøt L, Nsengimana J et al (2014) Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer. Ann Oncol 25:877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Desai NB, Scott SN, Zabor EC et al (2016) Genomic characterization of response to chemoradiation in urothelial bladder cancer. Cancer 122:3715

    Article  CAS  PubMed  Google Scholar 

  100. Andrews B, Shariat SF, Kim JH et al (2002) Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer. J Urol 167:1475

    Article  PubMed  Google Scholar 

  101. Chen FH, Crist SA, Zhang GJ et al (2002) Interleukin-6 production by human bladder tumor cell lines is up-regulated by bacillus Calmette-Guerin through nuclear factor-kappaB and Ap-1 via an immediate early pathway. J Urol 168:786

    Article  CAS  PubMed  Google Scholar 

  102. Riemann K, Becker L, Struwe H et al (2007) Insertion/deletion polymorphism in the promoter of NFKB1 as a potential molecular marker for the risk of recurrence in superficial bladder cancer. Int J Clin Pharmacol Ther 45:423

    Article  CAS  PubMed  Google Scholar 

  103. Bartsch G Jr, Mitra AP, Mitra SA et al (2016) Use of artificial intelligence and machine learning algorithms with gene expression profiling to predict recurrent nonmuscle invasive urothelial carcinoma of the bladder. J Urol 195:493

    Article  PubMed  Google Scholar 

  104. Masson-Lecomte A, Rava M, Real FX et al (2014) Inflammatory biomarkers and bladder cancer prognosis: a systematic review. Eur Urol 66:1078

    Article  CAS  PubMed  Google Scholar 

  105. Hilmy M, Campbell R, Bartlett JM et al (2006) The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration and COX-2 expression and survival in patients with transitional cell carcinoma of the urinary bladder. Br J Cancer 95:1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gakis G, Todenhöfer T, Renninger M et al (2011) Development of a new outcome prediction model in carcinoma invading the bladder based on preoperative serum C-reactive protein and standard pathological risk factors: the TNR-C score. BJU Int 108:1800

    Article  CAS  PubMed  Google Scholar 

  107. Yoshida S, Saito K, Koga F et al (2008) C-reactive protein level predicts prognosis in patients with muscle-invasive bladder cancer treated with chemoradiotherapy. BJU Int 101:978

    Article  PubMed  Google Scholar 

  108. Ishioka J, Saito K, Sakura M et al (2012) Development of a nomogram incorporating serum C-reactive protein level to predict overall survival of patients with advanced urothelial carcinoma and its evaluation by decision curve analysis. Br J Cancer 107:1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Nakagawa T, Hara T, Kawahara T et al (2013) Prognostic risk stratification of patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy. J Urol 189:1275

    Article  PubMed  Google Scholar 

  110. Bochner BH, Cote RJ, Weidner N et al (1995) Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Inst 87:1603

    Article  CAS  PubMed  Google Scholar 

  111. Bochner BH, Esrig D, Groshen S et al (1997) Relationship of tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer. Clin Cancer Res 3:1615

    CAS  PubMed  Google Scholar 

  112. Jaeger TM, Weidner N, Chew K et al (1995) Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer. J Urol 154:69

    Article  CAS  PubMed  Google Scholar 

  113. Shariat SF, Youssef RF, Gupta A et al (2010) Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol 183:1744

    Article  PubMed  Google Scholar 

  114. Crew JP, O’Brien T, Bradburn M et al (1997) Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. Cancer Res 57:5281

    CAS  PubMed  Google Scholar 

  115. Bernardini S, Fauconnet S, Chabannes E et al (2001) Serum levels of vascular endothelial growth factor as a prognostic factor in bladder cancer. J Urol 166:1275

    Article  CAS  PubMed  Google Scholar 

  116. Zu X, Tang Z, Li Y et al (2006) Vascular endothelial growth factor-C expression in bladder transitional cell cancer and its relationship to lymph node metastasis. BJU Int 98:1090

    Article  PubMed  Google Scholar 

  117. Herrmann E, Eltze E, Bierer S et al (2007) VEGF-C, VEGF-D and Flt-4 in transitional bladder cancer: relationships to clinicopathological parameters and long-term survival. Anticancer Res 27:3127

    PubMed  Google Scholar 

  118. Xia G, Kumar SR, Hawes D et al (2006) Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer. J Urol 175:1245

    Article  CAS  PubMed  Google Scholar 

  119. Mitra AP, Almal AA, George B et al (2006) The use of genetic programming in the analysis of quantitative gene expression profiles for identification of nodal status in bladder cancer. BMC Cancer 6:159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Shariat SF, Monoski MA, Andrews B et al (2003) Association of plasma urokinase-type plasminogen activator and its receptor with clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder. Urology 61:1053

    Article  PubMed  Google Scholar 

  121. Nguyen M, Watanabe H, Budson AE et al (1993) Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients. J Natl Cancer Inst 85:241

    Article  CAS  PubMed  Google Scholar 

  122. Gazzaniga P, Gandini O, Gradilone A et al (1999) Detection of basic fibroblast growth factor mRNA in urinary bladder cancer: correlation with local relapses. Int J Oncol 14:1123

    CAS  PubMed  Google Scholar 

  123. Chopin DK, Caruelle JP, Colombel M et al (1993) Increased immunodetection of acidic fibroblast growth factor in bladder cancer, detectable in urine. J Urol 150:1126

    Article  CAS  PubMed  Google Scholar 

  124. Grossfeld GD, Ginsberg DA, Stein JP et al (1997) Thrombospondin-1 expression in bladder cancer: Association with p53 alterations, tumor angiogenesis, and tumor progression. J Natl Cancer Inst 89:219

    Article  CAS  PubMed  Google Scholar 

  125. Mahnken A, Kausch I, Feller AC et al (2005) E-cadherin immunoreactivity correlates with recurrence and progression of minimally invasive transitional cell carcinomas of the urinary bladder. Oncol Rep 14:1065

    CAS  PubMed  Google Scholar 

  126. Mhawech-Fauceglia P, Fischer G, Beck A et al (2006) Raf1, Aurora-A/STK15 and E-cadherin biomarkers expression in patients with pTa/pT1 urothelial bladder carcinoma; a retrospective TMA study of 246 patients with long-term follow-up. Eur J Surg Oncol 32:439

    Article  CAS  PubMed  Google Scholar 

  127. Byrne RR, Shariat SF, Brown R et al (2001) E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup. J Urol 165:1473

    Article  CAS  PubMed  Google Scholar 

  128. Bringuier PP, Umbas R, Schaafsma HE et al (1993) Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res 53:3241

    CAS  PubMed  Google Scholar 

  129. Seiler R, Lam LL, Erho N et al (2016) Prediction of lymph node metastasis in patients with bladder cancer using whole transcriptome gene expression signatures. J Urol 196:1036

    Article  PubMed  Google Scholar 

  130. O’Brien T, Cranston D, Fuggle S et al (1995) Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res 55:510

    PubMed  Google Scholar 

  131. O’Brien TS, Fox SB, Dickinson AJ et al (1996) Expression of the angiogenic factor thymidine phosphorylase/platelet-derived endothelial cell growth factor in primary bladder cancers. Cancer Res 56:4799

    PubMed  Google Scholar 

  132. Aoki S, Yamada Y, Nakamura K et al (2006) Thymidine phosphorylase expression as a prognostic marker for predicting recurrence in primary superficial bladder cancer. Oncol Rep 16:279

    CAS  PubMed  Google Scholar 

  133. Nonomura N, Nakai Y, Nakayama M et al (2006) The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer. Int J Clin Oncol 11:297

    Article  CAS  PubMed  Google Scholar 

  134. Davies B, Waxman J, Wasan H et al (1993) Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion. Cancer Res 53:5365

    CAS  PubMed  Google Scholar 

  135. Gerhards S, Jung K, Koenig F et al (2001) Excretion of matrix metalloproteinases 2 and 9 in urine is associated with a high stage and grade of bladder carcinoma. Urology 57:675

    Article  CAS  PubMed  Google Scholar 

  136. Vasala K, Paakko P, Turpeenniemi-Hujanen T (2003) Matrix metalloproteinase-2 immunoreactive protein as a prognostic marker in bladder cancer. Urology 62:952

    Article  PubMed  Google Scholar 

  137. Slaton JW, Millikan R, Inoue K et al (2004) Correlation of metastasis related gene expression and relapse-free survival in patients with locally advanced bladder cancer treated with cystectomy and chemotherapy. J Urol 171:570

    Article  CAS  PubMed  Google Scholar 

  138. Guan KP, Ye HY, Yan Z et al (2003) Serum levels of endostatin and matrix metalloproteinase-9 associated with high stage and grade primary transitional cell carcinoma of the bladder. Urology 61:719

    Article  PubMed  Google Scholar 

  139. Szarvas T, Becker M, vom Dorp F et al (2010) Matrix metalloproteinase-7 as a marker of metastasis and predictor of poor survival in bladder cancer. Cancer Sci 101:1300

    Article  CAS  PubMed  Google Scholar 

  140. Szarvas T, Jäger T, Becker M et al (2011) Validation of circulating MMP-7 level as an independent prognostic marker of poor survival in urinary bladder cancer. Pathol Oncol Res 17:325

    Article  CAS  PubMed  Google Scholar 

  141. Roche Y, Pasquier D, Rambeaud JJ et al (2003) Fibrinogen mediates bladder cancer cell migration in an ICAM-1-dependent pathway. Thromb Haemost 89:1089

    Article  CAS  PubMed  Google Scholar 

  142. Ozer G, Altinel M, Kocak B et al (2003) Potential value of soluble intercellular adhesion molecule-1 in the serum of patients with bladder cancer. Urol Int 70:167

    Article  CAS  PubMed  Google Scholar 

  143. Mitra AP, Cote RJ (2011) Molecular signatures that predict nodal metastasis in bladder cancer: does the primary tumor tell tales? Expert Rev Anticancer Ther 11:849

    Article  CAS  PubMed  Google Scholar 

  144. Liebert M, Washington R, Wedemeyer G et al (1994) Loss of co-localization of a6b4 integrin and collagen VII in bladder cancer. Am J Pathol 144:787

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Grossman HB, Lee C, Bromberg J et al (2000) Expression of the a6b4 integrin provides prognostic information in bladder cancer. Oncol Rep 7:13

    CAS  PubMed  Google Scholar 

  146. Ahmadi H, Djaladat H, Cai J et al (2014) Precystectomy serum levels of carbohydrate antigen 19-9, carbohydrate antigen 125, and carcinoembryonic antigen: prognostic value in invasive urothelial carcinoma of the bladder. Urol Oncol 32:648

    Article  CAS  PubMed  Google Scholar 

  147. Bazargani ST, Clifford T, Djaladat H et al (2017) Association between epithelial tumor markers’ trends during the course of treatment and oncological outcomes in urothelial bladder cancer. Urol Oncol 35:609

    Article  Google Scholar 

  148. Bartsch G, Mitra AP, Cote RJ (2010) Expression profiling for bladder cancer: strategies to uncover prognostic factors. Expert Rev Anticancer Ther 10:1945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Birkhahn M, Mitra AP, Cote RJ (2007) Molecular markers for bladder cancer: the road to a multimarker approach. Expert Rev Anticancer Ther 7:1717

    Article  CAS  PubMed  Google Scholar 

  150. Sanchez-Carbayo M, Socci ND, Lozano J et al (2006) Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol 24:778

    Article  CAS  PubMed  Google Scholar 

  151. Kim WJ, Kim EJ, Kim SK et al (2010) Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer. Mol Cancer 9:3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Kim WJ, Kim SK, Jeong P et al (2011) A four-gene signature predicts disease progression in muscle invasive bladder cancer. Mol Med 17:478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Kim SK, Kim EJ, Leem SH et al (2010) Identification of S100A8-correlated genes for prediction of disease progression in non-muscle invasive bladder cancer. BMC Cancer 10:21

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Jeong P, Ha YS, Cho IC et al (2011) Three-gene signature predicts disease progression of non-muscle invasive bladder cancer. Oncol Lett 2:679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Ha YS, Kim JS, Yoon HY et al (2012) Novel combination markers for predicting progression of nonmuscle invasive bladder cancer. Int J Cancer 131:E501

    Article  CAS  PubMed  Google Scholar 

  156. Kim YJ, Yoon HY, Kim JS et al (2013) HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: Array-based DNA methylation and expression profiling. Int J Cancer 133:1135

    Article  CAS  PubMed  Google Scholar 

  157. Friedrich MG, Chandrasoma S, Siegmund KD et al (2005) Prognostic relevance of methylation markers in patients with non-muscle invasive bladder carcinoma. Eur J Cancer 41:2769

    Article  CAS  PubMed  Google Scholar 

  158. Su SF, de Castro Abreu AL, Chihara Y et al (2014) A panel of three markers hyper- and hypomethylated in urine sediments accurately predicts bladder cancer recurrence. Clin Cancer Res 20:1978

    Article  CAS  PubMed  Google Scholar 

  159. Mitra AP, Skinner EC, Miranda G et al (2013) A precystectomy decision model to predict pathological upstaging and oncological outcomes in clinical stage T2 bladder cancer. BJU Int 111:240

    Article  PubMed  Google Scholar 

  160. Ahmadi H, Mitra AP, Abdelsayed GA et al (2013) Principal component analysis based pre-cystectomy model to predict pathological stage in patients with clinical organ-confined bladder cancer. BJU Int 111:E167

    Article  PubMed  Google Scholar 

  161. Mitra AP, Bartsch CC, Cote RJ (2009) Strategies for molecular expression profiling in bladder cancer. Cancer Metastasis Rev 28:317

    Article  CAS  PubMed  Google Scholar 

  162. Mitra AP, Lam LL, Ghadessi M et al (2014) Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer. J Natl Cancer Inst 106:dju290

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Mitra SA, Mitra AP, Triche TJ (2012) A central role for long non-coding RNA in cancer. Front Genet 3:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Wang LC, Xylinas E, Kent MT et al (2014) Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder. Urol Oncol 32:433

    Article  CAS  PubMed  Google Scholar 

  165. Volkmer JP, Sahoo D, Chin RK et al (2012) Three differentiation states risk-stratify bladder cancer into distinct subtypes. Proc Natl Acad Sci U S A 109:2078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Choi W, Porten S, Kim S et al (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25:152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Mitra AP, Lerner SP (2015) Potential role for targeted therapy in muscle-invasive bladder cancer: lessons from the Cancer Genome Atlas and beyond. Urol Clin North Am 42:201

    Article  PubMed  Google Scholar 

  168. Srivastava S, Gray JW, Reid BJ et al (2008) Translational Research Working Group developmental pathway for biospecimen-based assessment modalities. Clin Cancer Res 14:5672

    Article  PubMed  PubMed Central  Google Scholar 

  169. Khleif SN, Doroshow JH, Hait WN (2010) AACR-FDA-NCI Cancer Biomarkers Collaborative consensus report: advancing the use of biomarkers in cancer drug development. Clin Cancer Res 16:3299

    Article  CAS  PubMed  Google Scholar 

  170. Kattan MW, Hess KR, Amin MB et al (2016) American Joint Committee on Cancer acceptance criteria for inclusion of risk models for individualized prognosis in the practice of precision medicine. CA Cancer J Clin 66:370

    Article  PubMed  PubMed Central  Google Scholar 

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Funding Acknowledgement

This research was not sponsored by any funding agency in the public, commercial, or not-for-profit sectors.

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  1. Institute of Urology, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Suite 7416, MC 9178, Los Angeles, CA, 90033, USA

    Anirban P. Mitra & Siamak Daneshmand

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  1. Anirban P. Mitra
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  2. Siamak Daneshmand
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Correspondence to Anirban P. Mitra .

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  1. Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    Siamak Daneshmand

  2. City of Hope National Medical Center, Duarte, CA, USA

    Kevin G. Chan

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Mitra, A.P., Daneshmand, S. (2018). Molecular Prognostication in Bladder Cancer. In: Daneshmand, S., Chan, K. (eds) Genitourinary Cancers . Cancer Treatment and Research, vol 175. Springer, Cham. https://doi.org/10.1007/978-3-319-93339-9_8

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