Top

Published in:

Open Access 01-01-2019 | Topic Paper

Molecular markers in bladder cancer

Authors: Francesco Soria, Laura-Maria Krabbe, Tilman Todenhöfer, Jakub Dobruch, Anirban P. Mitra, Brant A. Inman, Kilian M. Gust, Yair Lotan, Shahrokh F. Shariat

Published in: World Journal of Urology | Issue 1/2019

Abstract

Purpose

Use of molecular markers in urine, tissue or blood offers potential opportunities to improve understanding of bladder cancer biology which may help identify disease earlier, risk stratify patients, improve prediction of outcomes or help target therapy.

Methods

A review of the published literature was performed, without restriction of time.

Results

Despite the fast-growing literature about the topic and the approval of several urinary biomarkers for use in clinical practice, they have not reached the level of evidence for widespread utilization. Biomarkers could be used in different clinical scenarios, mainly to overcome the limitations of current diagnostic, predictive, and prognostic tools. They have been evaluated to detect bladder cancer in asymptomatic populations or those with hematuria and in surveillance of disease as adjuncts to cystoscopy. There is also a potential role as prognosticators of disease recurrence, progression and survival both in patients with non-invasive cancers and in those with advanced disease. Finally, they promise to be helpful in predicting the response to local and/or systemic chemotherapy and/or immunotherapy.

Conclusions

To date, due to the lack of high-quality prospective trials, the level of evidence provided by the current literature remains low and, therefore, the potential of biomarkers exceeds utilization in clinical practice.

Kamat AM, Hegarty PK, Gee JR, Clark PE, Svatek RS, Hegarty N et al (2013) ICUD–EAU international consultation on bladder cancer 2012: screening, diagnosis, and molecular markers. Eur Urol 63:4–15. https://doi.org/10.1016/j.eururo.2012.09.057 CrossRefPubMed

Karakiewicz PI, Shariat SF, Palapattu GS, Perrotte P, Lotan Y, Rogers CG et al (2006) Precystectomy nomogram for prediction of advanced bladder cancer stage. Eur Urol 50:1254–1260. https://doi.org/10.1016/j.eururo.2006.06.010 (Discussion 1261–2) CrossRefPubMed

Tilki D, Burger M, Dalbagni G, Grossman HB, Hakenberg OW, Palou J et al (2011) Urine markers for detection and surveillance of non-muscle-invasive bladder cancer. Eur Urol 60:484–492. https://doi.org/10.1016/j.eururo.2011.05.053 CrossRefPubMed

Bensalah K, Montorsi F, Shariat SF (2007) Challenges of cancer biomarker profiling. Eur Urol 52:1601–1609. https://doi.org/10.1016/j.eururo.2007.09.036 CrossRefPubMed

Shariat SF, Lotan Y, Vickers A, Karakiewicz PI, Schmitz-Drager BJ, Goebell PJ et al (2010) Statistical consideration for clinical biomarker research in bladder cancer. Urol Oncol 28:389–400. https://doi.org/10.1016/j.urolonc.2010.02.011 CrossRefPubMedPubMedCentral

Shariat SF, Zlotta AR, Ashfaq R, Sagalowsky AI, Lotan Y (2007) Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness. Mod Pathol 20:445–459. https://doi.org/10.1038/modpathol.3800757 CrossRefPubMed

Karam JA, Lotan Y, Karakiewicz PI, Ashfaq R, Sagalowsky AI, Roehrborn CG et al (2007) Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol 8:128–136. https://doi.org/10.1016/S1470-2045(07)70002-5 CrossRefPubMed

Friedman GD, Hiatt RA, Quesenberry CP Jr, Selby JV, Weiss NS (1995) Problems in assessing screening experience in observational studies of screening efficacy: example of urinalysis screening for bladder cancer. J Med Screen 2:219–223. https://doi.org/10.1177/096914139500200409 CrossRefPubMed

Krabbe L-M, Svatek RS, Shariat SF, Messing E, Lotan Y (2015) Bladder cancer risk: use of the PLCO and NLST to identify a suitable screening cohort. Urol Oncol 33:65.e19–65.e25. https://doi.org/10.1016/j.urolonc.2014.06.009 CrossRef

10.

Lotan Y, Elias K, Svatek RS, Bagrodia A, Nuss G, Moran B et al (2009) Bladder cancer screening in a high risk asymptomatic population using a point of care urine based protein tumor marker. J Urol 182:52–57. https://doi.org/10.1016/j.juro.2009.02.142 (Discussion 58) CrossRefPubMed

11.

Starke N, Singla N, Haddad A, Lotan Y (2016) Long-term outcomes in a high-risk bladder cancer screening cohort. BJU Int 117:611–617. https://doi.org/10.1111/bju.13154 CrossRefPubMed

12.

Mariani AJ, Mariani MC, Macchioni C, Stams UK, Hariharan A, Moriera A (1989) The significance of adult hematuria: 1000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. J Urol 141:350–355CrossRefPubMed

13.

Fajkovic H, Halpern JA, Cha EK, Bahadori A, Chromecki TF, Karakiewicz PI et al (2011) Impact of gender on bladder cancer incidence, staging, and prognosis. World J Urol 29:457–463. https://doi.org/10.1007/s00345-011-0709-9 CrossRefPubMed

14.

Cohen RA, Brown RS (2003) Clinical practice. Microscopic hematuria. N Engl J Med 348:2330–2338. https://doi.org/10.1056/NEJMcp012694 CrossRefPubMed

15.

Lotan Y, Svatek RS, Krabbe LM, Xylinas E, Klatte T, Shariat SF (2014) Prospective external validation of a bladder cancer detection model. J Urol 192:1343–1348. https://doi.org/10.1016/j.juro.2014.05.087 CrossRefPubMed

16.

Elias K, Svatek RS, Gupta S, Ho R, Lotan Y (2010) High-risk patients with hematuria are not evaluated according to guideline recommendations. Cancer 116:2954–2959. https://doi.org/10.1002/cncr.25048 CrossRefPubMed

17.

Cha EK, Tirsar LA, Schwentner C, Christos PJ, Mian C, Hennenlotter J et al (2012) Immunocytology is a strong predictor of bladder cancer presence in patients with painless hematuria: a multicentre study. Eur Urol 61:185–192. https://doi.org/10.1016/j.eururo.2011.08.073 CrossRefPubMed

18.

Beukers W, Kandimalla R, van Houwelingen D, Kovacic H, Chin JF, Lingsma HF et al (2013) The use of molecular analyses in voided urine for the assessment of patients with hematuria. PLoS One 8:e77657. https://doi.org/10.1371/journal.pone.0077657 CrossRefPubMedPubMedCentral

19.

van der Aa MNM, Steyerberg EW, Bangma C, van Rhijn BWG, Zwarthoff EC, van der Kwast TH (2010) Cystoscopy revisited as the gold standard for detecting bladder cancer recurrence: diagnostic review bias in the randomized, prospective CEFUB trial. J Urol 183:76–80. https://doi.org/10.1016/j.juro.2009.08.150 CrossRefPubMed

20.

Messer J, Shariat SF, Brien JC, Herman MP, Ng CK, Scherr DS et al (2011) Urinary cytology has a poor performance for predicting invasive or high-grade upper-tract urothelial carcinoma. BJU Int 108:701–705. https://doi.org/10.1111/j.1464-410X.2010.09899.x CrossRefPubMed

21.

Karakiewicz PI, Benayoun S, Zippe C, Lüdecke G, Boman H, Sanchez-Carbayo M et al (2006) Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder. BJU Int 97:997–1001. https://doi.org/10.1111/j.1464-410X.2006.06036.x CrossRefPubMed

22.

Yossepowitch O, Herr HW, Donat SM (2007) Use of urinary biomarkers for bladder cancer surveillance: patient perspectives. J Urol 177:1277–1282. https://doi.org/10.1016/j.juro.2006.11.066 (Discussion 1282) CrossRefPubMed

23.

Miyanaga N, Akaza H, Tsukamoto S, Shimazui T, Ohtani M, Ishikawa S et al (2003) Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection. Int J Clin Oncol 8:369–373. https://doi.org/10.1007/s10147-003-0357-1 CrossRefPubMed

24.

Kavalieris L, O’Sullivan P, Frampton C, Guilford P, Darling D, Jacobson E et al (2017) Performance characteristics of a multigene urine biomarker test for monitoring for recurrent urothelial carcinoma in a multicenter study. J Urol 197:1419–1426. https://doi.org/10.1016/j.juro.2016.12.010 CrossRefPubMed

25.

Horstmann M, Patschan O, Hennenlotter J, Senger E, Feil G, Stenzl A (2009) Combinations of urine-based tumour markers in bladder cancer surveillance. Scand J Urol Nephrol 43:461–466. https://doi.org/10.3109/00365590903296837 CrossRefPubMed

26.

Babjuk M, Soukup V, Pešl M, Koštířová M, Drncová E, Smolová H et al (2008) Urinary cytology and quantitative BTA and UBC tests in surveillance of patients with pTapT1 bladder urothelial carcinoma. Urology 71:718–722. https://doi.org/10.1016/j.urology.2007.12.021 CrossRefPubMed

27.

Todenhöfer T, Hennenlotter J, Esser M, Mohrhardt S, Aufderklamm S, Böttge J et al (2014) Stepwise application of urine markers to detect tumor recurrence in patients undergoing surveillance for non-muscle-invasive bladder cancer. Dis Markers 2014:973406. https://doi.org/10.1155/2014/973406 CrossRefPubMedPubMedCentral

28.

Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM et al (2016) EAU guidelines on non–muscle-invasive urothelial carcinoma of the bladder: update. Eur Urol 71:447–461. https://doi.org/10.1016/j.eururo.2016.05.041 CrossRefPubMed

29.

Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR et al (2016) Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol 196:1021–1029. https://doi.org/10.1016/j.juro.2016.06.049 CrossRefPubMed

30.

Kamat AM, Willis DL, Dickstein RJ, Anderson R, Nogueras-González G, Katz RL et al (2016) Novel fluorescence in situ hybridization-based definition of bacille Calmette–Guérin (BCG) failure for use in enhancing recruitment into clinical trials of intravesical therapies. BJU Int 117:754–760. https://doi.org/10.1111/bju.13186 CrossRefPubMed

31.

Schlomer BJ, Ho R, Sagalowsky A, Ashfaq R, Lotan Y (2010) Prospective validation of the clinical usefulness of reflex fluorescence in situ hybridization assay in patients with atypical cytology for the detection of urothelial carcinoma of the bladder. J Urol 183:62–67. https://doi.org/10.1016/j.juro.2009.08.157 CrossRefPubMed

32.

Odisho AY, Berry AB, Ahmad AE, Cooperberg MR, Carroll PR, Konety BR (2013) Reflex ImmunoCyt testing for the diagnosis of bladder cancer in patients with atypical urine cytology. Eur Urol 63:936–940. https://doi.org/10.1016/j.eururo.2012.04.019 CrossRefPubMed

33.

Shariat SF, Weizer AZ, Green A, Laucirica R, Frolov A, Wheeler TM et al (2000) Prognostic value of P53 nuclear accumulation and histopathologic features in T1 transitional cell carcinoma of the urinary bladder. Urology 56:735–740CrossRefPubMed

34.

Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y (2007) Predictive value of cell cycle biomarkers in nonmuscle invasive bladder transitional cell carcinoma. J Urol 177:481–487. https://doi.org/10.1016/j.juro.2006.09.038 (Discussion 487) CrossRefPubMed

35.

Shariat SF, Chade DC, Karakiewicz PI, Ashfaq R, Isbarn H, Fradet Y et al (2010) Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J Urol 183:68–75. https://doi.org/10.1016/j.juro.2009.08.115 CrossRefPubMed

36.

Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP (2003) Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology 61:1140–1145CrossRefPubMed

37.

Fritsche H-M, Burger M, Svatek RS, Jeldres C, Karakiewicz PI, Novara G et al (2010) Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol 57:300–309. https://doi.org/10.1016/j.eururo.2009.09.024 CrossRefPubMed

38.

Du J, Wang S, Yang Q, Chen Q, Yao X (2016) p53 status correlates with the risk of progression in stage T1 bladder cancer: a meta-analysis. World J Surg Oncol 14:137. https://doi.org/10.1186/s12957-016-0890-9 CrossRefPubMedPubMedCentral

39.

Zhou X, Zhang G, Tian Y (2015) p53 status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with bacillus Calmette–Guérin: a meta-analysis. PLoS One 10:e0119476. https://doi.org/10.1371/journal.pone.0119476 CrossRefPubMedPubMedCentral

40.

Tetu B, Fradet Y, Allard P, Veilleux C, Roberge N, Bernard P (1996) Prevalence and clinical significance of HER/2neu, p53 and Rb expression in primary superficial bladder cancer. J Urol 155:1784–1788CrossRefPubMed

41.

Shariat SF, Ashfaq R, Karakiewicz PI, Saeedi O, Sagalowsky AI, Lotan Y (2007) Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer 109:1106–1113. https://doi.org/10.1002/cncr.22521 CrossRefPubMed

42.

Shariat SF, Lotan Y, Saboorian H, Khoddami SM, Roehrborn CG, Slawin KM et al (2004) Survivin expression is associated with features of biologically aggressive prostate carcinoma. Cancer 100:751–757. https://doi.org/10.1002/cncr.20039 CrossRefPubMed

43.

Fristrup N, Ulhøi BP, Birkenkamp-Demtröder K, Mansilla F, Sanchez-Carbayo M, Segersten U et al (2012) Cathepsin E, maspin, Plk1, and survivin are promising prognostic protein markers for progression in non-muscle invasive bladder cancer. Am J Pathol 180:1824–1834. https://doi.org/10.1016/j.ajpath.2012.01.023 CrossRefPubMed

44.

Jeon C, Kim M, Kwak C, Kim HH, Ku JH (2013) Prognostic role of survivin in bladder cancer: a systematic review and meta-analysis. PLoS One 8:e76719. https://doi.org/10.1371/journal.pone.0076719 CrossRefPubMedPubMedCentral

45.

Xi RC, Sheng YR, Chen WH, Sheng L, Gang JJ, Tong Z et al (2013) Expression of survivin and livin predicts early recurrence in non-muscle invasive bladder cancer. J Surg Oncol 107:550–554. https://doi.org/10.1002/jso.23272 CrossRefPubMed

46.

Ajili F, Kaabi B, Darouiche A, Tounsi H, Kourda N, Chebil M et al (2012) Prognostic value of Bcl-2 and Bax tumor cell expression in patients with non muscle-invasive bladder cancer receiving bacillus Calmette–Guerin immunotherapy. Ultrastruct Pathol 36:31–39. https://doi.org/10.3109/01913123.2011.620221 CrossRefPubMed

47.

Byrne RR, Shariat SF, Brown R, Kattan MW, Morton RAJR, Wheeler TM et al (2001) E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup. J Urol 165:1473–1479CrossRefPubMed

48.

Xylinas E, Kluth LA, Lotan Y, Daneshmand S, Rieken M, Karakiewicz PI et al (2014) Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder. Urol Oncol 32:230–242. https://doi.org/10.1016/j.urolonc.2013.06.009 CrossRefPubMed

49.

Zlotta A, Alkhateeb S, Neill M, Bar-Moshe S, Rhijn B, Kakiashvili D et al (2011) Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical bacille Calmette–Guérin. Urol Ann 3:119. https://doi.org/10.4103/0974-7796.84954 CrossRefPubMedPubMedCentral

50.

Passoni N, Gayed B, Kapur P, Sagalowsky AI, Shariat SF, Lotan Y (2016) Cell-cycle markers do not improve discrimination of EORTC and CUETO risk models in predicting recurrence and progression of non–muscle-invasive high-grade bladder cancer. Urol Oncol Semin Orig Investig 34:485.e7–485.e14. https://doi.org/10.1016/j.urolonc.2016.05.014 CrossRef

51.

Shariat SF, Tokunaga H, Zhou J, Kim J, Ayala GE, Benedict WF et al (2004) p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer. J Clin Oncol 22:1014–1024CrossRefPubMed

52.

Shariat SF, Lotan Y, Karakiewicz PI, Ashfaq R, Isbarn H, Fradet Y et al (2009) p53 predictive value for pT1-2 N0 disease at radical cystectomy. J Urol 182:907–913. https://doi.org/10.1016/j.juro.2009.05.024 CrossRefPubMed

53.

Stadler WM, Lerner SP, Groshen S, Stein JP, Shi SR, Raghavan D 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 29:3443–3449. https://doi.org/10.1200/jco.2010.34.4028 CrossRefPubMedPubMedCentral

54.

Chatterjee SJ, Datar R, Youssefzadeh D, George B, Goebell PJ, Stein JP et al (2004) Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma. J Clin Oncol 22:1007–1013. https://doi.org/10.1200/JCO.2004.05.174 CrossRefPubMed

55.

Shariat SF, Karakiewicz PI, Ashfaq R, Lerner SP, Palapattu GS, Cote RJ et al (2008) Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy. Cancer 112:315–325. https://doi.org/10.1002/cncr.23162 CrossRefPubMed

56.

Shariat SF, Chromecki TF, Cha EK, Karakiewicz PI, Sun M, Fradet Y et al (2012) Risk stratification of organ confined bladder cancer after radical cystectomy using cell cycle related biomarkers. J Urol 187:457–462. https://doi.org/10.1016/j.juro.2011.10.031 CrossRefPubMed

57.

Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y (2006) Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis. Hum Pathol 37:1568–1576. https://doi.org/10.1016/j.humpath.2006.05.017 CrossRefPubMed

58.

Shariat SF, Karakiewicz PI, Godoy G, Karam JA, Ashfaq R, Fradet Y et al (2009) Survivin as a prognostic marker for urothelial carcinoma of the bladder: a multicenter external validation study. Clin Cancer Res 15:7012–7019. https://doi.org/10.1158/1078-0432.CCR-08-2554 CrossRefPubMed

59.

Zu X, Tang Z, Li Y, Gao N, Ding J, Qi L (2006) Vascular endothelial growth factor-C expression in bladder transitional cell cancer and its relationship to lymph node metastasis. BJU Int 98:1090–1093. https://doi.org/10.1111/j.1464-410X.2006.06446.x CrossRefPubMed

60.

Herrmann E, Eltze E, Bierer S, Köpke T, Görge T, Neumann J et al (2007) VEGF-C, VEGF-D and Flt-4 in transitional bladder cancer: relationships to clinicopathological parameters and long-term survival. Anticancer Res 27:3127–3133PubMed

61.

Margulis V, Lotan Y, Karakiewicz PI, Fradet Y, Ashfaq R, Capitanio U et al (2009) Multi-institutional validation of the predictive value of Ki-67 labeling index in patients with urinary bladder cancer. J Natl Cancer Inst 101:114–119. https://doi.org/10.1093/jnci/djn451 CrossRefPubMed

62.

Margulis V, Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y (2006) Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease. Clin Cancer Res 12:7369–7373. https://doi.org/10.1158/1078-0432.CCR-06-1472 CrossRefPubMed

63.

Bartsch G, Mitra AP, Cote RJ (2010) Expression profiling for bladder cancer: strategies to uncover prognostic factors. Expert Rev Anticancer Ther 10:1945–1954. https://doi.org/10.1586/era.10.131 CrossRefPubMedPubMedCentral

64.

Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507:315–322. https://doi.org/10.1038/nature12965 CrossRef

65.

Oneyama C, Ikeda J, Okuzaki D, Suzuki K, Kanou T, Shintani Y et al (2011) MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways. Oncogene 30:3489–3501. https://doi.org/10.1038/onc.2011.63 CrossRefPubMed

66.

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 42:201–215. https://doi.org/10.1016/j.ucl.2015.01.003 CrossRefPubMed

67.

Shariat SF, Kim J, Nguyen C, Wheeler TM, Lerner SP, Slawin KM (2003) Correlation of preoperative levels of IGF-I and IGFBP-3 with pathologic parameters and clinical outcome in patients with bladder cancer. Urology 61:359–364CrossRefPubMed

68.

Kim JH, Shariat SF, Kim IY, Menesses-Diaz A, Tokunaga H, Wheeler TM et al (2001) Predictive value of expression of transforming growth factor-β1 and its receptors in transitional cell carcinoma of the urinary bladder. Cancer 92:1475–1483. https://doi.org/10.1002/1097-0142(20010915)92:6%3c1475:AID-CNCR1472%3e3.0.CO;2-X [pii] CrossRefPubMed

69.

Shariat SF, Kim JH, Andrews B, Kattan MW, Wheeler TM, Kim IY et al (2001) Preoperative plasma levels of transforming growth factor β1 strongly predict clinical outcome in patients with bladder carcinoma. Cancer 92:2985–2992. https://doi.org/10.1002/1097-0142(20011215)92:12%3c2985:AID-CNCR10175%3e3.0.CO;2-5 [pii] CrossRefPubMed

70.

Andrews B, Shariat SF, Kim JH, Wheeler TM, Slawin KM, Lerner SP (2002) Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer. J Urol 167:1475–1481. https://doi.org/10.1016/S0022-5347(05)65348-7 [pii] CrossRefPubMed

71.

Masson-Lecomte A, Rava M, Real FX, Hartmann A, Allory Y, Malats N (2014) Inflammatory biomarkers and bladder cancer prognosis: a systematic review. Eur Urol 66:1078–1091. https://doi.org/10.1016/j.eururo.2014.07.033 CrossRefPubMed

72.

Mbeutcha A, Shariat SF, Rieken M, Rink M, Xylinas E, Seitz C et al (2016) Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer. Urol Oncol 34:483.e17–483.e24. https://doi.org/10.1016/j.urolonc.2016.05.013 CrossRef

73.

Bernardini S, Fauconnet S, Chabannes E, Henry PC, Adessi G, Bittard H (2001) Serum levels of vascular endothelial growth factor as a prognostic factor in bladder cancer. J Urol 166:1275–1279. https://doi.org/10.1016/S0022-5347(05)65752-7 [pii] CrossRefPubMed

74.

Rink M, Chun FK, Minner S, Friedrich M, Mauermann O, Heinzer H et al (2011) Detection of circulating tumour cells in peripheral blood of patients with advanced non-metastatic bladder cancer. BJU Int 107:1668–1675. https://doi.org/10.1111/j.1464-410X.2010.09562.x CrossRefPubMed

75.

Rink M, Chun FK, Dahlem R, Soave A, Minner S, Hansen J et al (2012) Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. Eur Urol 61:810–817. https://doi.org/10.1016/j.eururo.2012.01.017 CrossRefPubMed

76.

Esrig D, Elmajian D, Groshen S, Freeman JA, Stein JP, Chen SC et al (1994) Accumulation of nuclear p53 and tumor progression in bladder cancer. N Engl J Med 331:1259–1264CrossRefPubMed

77.

Plimack ER, Dunbrack RL, Brennan TA, Andrake MD, Zhou Y, Serebriiskii IG et al (2015) Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol 68:959–967. https://doi.org/10.1016/j.eururo.2015.07.009 CrossRefPubMedPubMedCentral

78.

Liu D, Plimack ER, Hoffman-Censits J, Garraway LA, Bellmunt J, Van Allen E et al (2016) Clinical validation of chemotherapy response biomarker ERCC2 in muscle-invasive urothelial bladder carcinoma. JAMA Oncol 2:1094–1096. https://doi.org/10.1001/jamaoncol.2016.1056 CrossRefPubMedPubMedCentral

79.

Xu ZC, Cai HZ, Li X, Xu WZ, Xu T, Yu B et al (2016) ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer. Genet Mol Res. https://doi.org/10.4238/gmr.15027801 CrossRefPubMed

80.

Iyer G, Hanrahan AJ, Milowsky MI, Al-Ahmadie H, Scott SN, Janakiraman M et al (2012) Genome sequencing identifies a basis for everolimus sensitivity. Science 338:221. https://doi.org/10.1126/science.1226344 CrossRefPubMedPubMedCentral

81.

Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A et al (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920. https://doi.org/10.1016/S0140-6736(16)00561-4 CrossRefPubMedPubMedCentral

82.

Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J et al (2017) Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol 18:312–322. https://doi.org/10.1016/S1470-2045(17)30065-7 CrossRefPubMed

83.

Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L et al (2017) Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376:1015–1026. https://doi.org/10.1056/NEJMoa1613683 CrossRefPubMedPubMedCentral

84.

Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J et al (2017) Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 389:67–76. https://doi.org/10.1016/S0140-6736(16)32455-2 CrossRefPubMed

85.

Powles T, O’Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ et al (2017) Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2017.2411 CrossRefPubMedPubMedCentral

86.

Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K et al (2017) Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase Ib study. J Clin Oncol 35:2117–2124. https://doi.org/10.1200/JCO.2016.71.6795 CrossRefPubMedPubMedCentral

87.

Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E et al (2016) Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol 17:1590–1598. https://doi.org/10.1016/S1470-2045(16)30496-X CrossRefPubMedPubMedCentral

88.

Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J et al (2016) Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint, in patients with advanced urothelial bladder cancer. J Clin Oncol 34:3119–3125. https://doi.org/10.1200/JCO.2016.67.9761 CrossRefPubMedPubMedCentral

89.

Xylinas E, Robinson BD, Kluth LA, Volkmer BG, Hautmann R, Küfer R et al (2014) Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. Eur J Surg Oncol 40:121–127. https://doi.org/10.1016/j.ejso.2013.08.023 CrossRefPubMed

90.

Shariat SF, Gust KM (2017) Immune therapy meets precision medicine. Lancet Oncol 18:271–273. https://doi.org/10.1016/S1470-2045(17)30098-0 CrossRefPubMed

Title: Molecular markers in bladder cancer
Authors: Francesco Soria
Laura-Maria Krabbe
Tilman Todenhöfer
Jakub Dobruch
Anirban P. Mitra
Brant A. Inman
Kilian M. Gust
Yair Lotan
Shahrokh F. Shariat
Publication date: 01-01-2019
Publisher: Springer Berlin Heidelberg
Published in: World Journal of Urology / Issue 1/2019
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-018-2503-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Molecular markers in bladder cancer

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2019

Functional follow-up after Advance® and Advance XP® male sling surgery: assessment of predictive factors

Pressure matters 2: intrarenal pressure ranges during upper-tract endourological procedures

SIU-ICUD recommendations on bladder cancer: systemic therapy for metastatic bladder cancer

Epidemiology, biology and treatment of sarcomatoid RCC: current state of the art

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

Epidemiology, prevention, screening, diagnosis, and evaluation: update of the ICUD–SIU joint consultation on bladder cancer