The Role of Urologist

  • Mihai Dorin Vartolomei
  • Shahrokh F. ShariatEmail author


The urologist will have a key-role in the prevention and management of bladder cancer (BC), also in the future. This chapter focuses on the possible changes in whom the urologist will be involved. First subchapter discusses the nature of BC as a preventable disease. Cigarette smoking is the most preventable cause of BC and more efforts should be done to encourage smoking cessation among general population and newly diagnosed BC patients. Second subchapter focuses on early detection of BC. In future, improved definition of high risk populations suited for screening together with the development of integrated multi-markers models may improve early detection of urothelial cancer. The third subchapter is dedicated to intravesical therapies and how can be done best in the management of BC. BCG is still the best adjuvant treatment for intermediate and high-risk NMIBC, for patients who experience BCG failure, to date; only Valrubicin is FDA approved therapy. Forth subchapter is focused on precision medicine and immunotherapy for BC patients. PD-1/PD-L1 checkpoints blockades are approved therapies in second line metastatic BC and in first line cisplatin-ineligible BC because of their high efficacy and tolerability. Knowledge of the side effects and experience in their management is essential to optimal patient care.


Bladder cancer prevention Markers BCG strain Immunotherapy Future 


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Wang S-C, Sung W-W, Kao Y-L, Hsieh T-Y, Chen W-J, Chen S-L, et al. The gender difference and mortality-to-incidence ratio relate to health care disparities in bladder cancer: national estimates from 33 countries. Sci Rep. 2017;7(1):4360.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Yeung C, Dinh T, Lee J. The health economics of bladder cancer: an updated review of the published literature. PharmacoEconomics. 2014;32(11):1093–104.PubMedCrossRefGoogle Scholar
  4. 4.
    Burger M, Catto JWF, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011;306(7):737–45.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Sosnowski R, Przewoźniak K. The role of the urologist in smoking cessation: why is it important? Urol Oncol. 2015;33(1):30–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Colt JS, Friesen MC, Stewart PA, Donguk P, Johnson A, Schwenn M, et al. A case-control study of occupational exposure to metalworking fluids and bladder cancer risk among men. Occup Environ Med. 2014;71(10):667–74.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Pesch B, Taeger D, Johnen G, Gawrych K, Bonberg N, Schwentner C, et al. Screening for bladder cancer with urinary tumor markers in chemical workers with exposure to aromatic amines. Int Arch Occup Environ Health. 2014;87(7):715–24.PubMedCrossRefGoogle Scholar
  9. 9.
    Egbers L, Grotenhuis AJ, Aben KK, Alfred Witjes J, Kiemeney LA, Vermeulen SH. The prognostic value of family history among patients with urinary bladder cancer. Int J Cancer. 2015;136(5):1117–24.PubMedCrossRefGoogle Scholar
  10. 10.
    Corral R, Lewinger JP, Van Den Berg D, Joshi AD, Yuan J-M, Gago-Dominguez M, et al. Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai. Int J Cancer. 2014;135(2):335–47.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Figueroa JD, Middlebrooks CD, Banday AR, Ye Y, Garcia-Closas M, Chatterjee N, et al. Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry. Hum Mol Genet. 2016;25(6):1203–14.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Steinmaus C, Ferreccio C, Acevedo J, Yuan Y, Liaw J, Durán V, et al. Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure. Cancer Epidemiol Biomark Prev. 2014;23(8):1529–38.CrossRefGoogle Scholar
  13. 13.
    Liu H, Wang X-C, Hu G-H, Guo Z-F, Lai P, Xu L, et al. Fruit and vegetable consumption and risk of bladder cancer: an updated meta-analysis of observational studies. Eur J Cancer Prev. 2015;24(6):508–16.PubMedCrossRefGoogle Scholar
  14. 14.
    Miyazaki J, Nishiyama H. Epidemiology of urothelial carcinoma. Int J Urol. 2017;24(10):730–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJL, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009;6(4):e1000058.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    WHO. Global estimate of the burden of disease from second-hand smoke [Internet]. WHO. [cited 2017 July 10].
  17. 17.
    Main—Mortality from smoking in developed countries [Internet]. [cited 2017 July 10].
  18. 18.
    Sosnowski R, Verze P, De Nunzio C, Bjurlin MA. Re: Marcus G. Cumberbatch, Matteo Rota, James W.F. Catto, Carlo La Vecchia. The role of tobacco smoke in bladder and kidney carcinogenesis: a comparison of exposures and meta-analysis of incidence and mortality risks. Eur Urol 2016;70:458-66: smoking cessation and urology: a new domain for prevention and treatment. Eur Urol. 2016;70(4):e102–3.PubMedCrossRefGoogle Scholar
  19. 19.
    Bjurlin MA, Cohn MR, Kim DY, Freeman VL, Lombardo L, Hurley SD, et al. Brief smoking cessation intervention: a prospective trial in the urology setting. J Urol. 2013;189(5):1843–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Lindson-Hawley N, Hartmann-Boyce J, Fanshawe TR, Begh R, Farley A, Lancaster T. Interventions to reduce harm from continued tobacco use. Cochrane Database Syst Rev. 2016;10:CD005231.PubMedGoogle Scholar
  21. 21.
    Chang P-Y, Lo P-C, Chang H-C, Hsueh K-C, Tsai Y-W. Comparative effectiveness of smoking cessation medications: a national prospective cohort from Taiwan. PLoS One. 2016;11(11):e0166992.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Lancaster T, Stead LF. Individual behavioural counselling for smoking cessation. Cochrane Database Syst Rev. 2017;3:CD001292.PubMedGoogle Scholar
  23. 23.
    Furberg H, Schoenberg M. The effect of smoking and timing of smoking cessation on clinical outcome in non-muscle-invasive bladder cancer. Urol Oncol. 2015;33(1):49.PubMedCrossRefGoogle Scholar
  24. 24.
    Rink M, Zabor EC, Furberg H, Xylinas E, Ehdaie B, Novara G, et al. Impact of smoking and smoking cessation on outcomes in bladder cancer patients treated with radical cystectomy. Eur Urol. 2013;64(3):456–64.PubMedCrossRefGoogle Scholar
  25. 25.
    Rink M, Furberg H, Zabor EC, Xylinas E, Babjuk M, Pycha A, et al. Impact of smoking and smoking cessation on oncologic outcomes in primary non-muscle-invasive bladder cancer. Eur Urol. 2013;63(4):724–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Kroeger N, Klatte T, Birkhäuser FD, Rampersaud EN, Seligson DB, Zomorodian N, et al. Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival. Cancer. 2012;118(7):1795–802.PubMedCrossRefGoogle Scholar
  27. 27.
    Crivelli JJ, Xylinas E, Kluth LA, Rieken M, Rink M, Shariat SF. Effect of smoking on outcomes of urothelial carcinoma: a systematic review of the literature. Eur Urol. 2014;65(4):742–54.PubMedCrossRefGoogle Scholar
  28. 28.
    Bjurlin MA, Goble SM, Hollowell CMP. Smoking cessation assistance for patients with bladder cancer: a national survey of American urologists. J Urol. 2010;184(5):1901–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Reda AA, Kotz D, Evers SMAA, van Schayck CP. Healthcare financing systems for increasing the use of tobacco dependence treatment. Cochrane Database Syst Rev. 2012;(6):CD004305.Google Scholar
  30. 30.
    Gore JL, Lai J, Setodji CM, Litwin MS, Saigal CS. Urologic diseases in America project. Mortality increases when radical cystectomy is delayed more than 12 weeks: results from a surveillance, epidemiology, and end results-medicare analysis. Cancer. 2009;115(5):988–96.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Wallace DMA, Bryan RT, Dunn JA, Begum G, Bathers S. West Midlands urological research group. Delay and survival in bladder cancer. BJU Int. 2002;89(9):868–78.PubMedCrossRefGoogle Scholar
  32. 32.
    Hollenbeck BK, Dunn RL, Ye Z, Hollingsworth JM, Skolarus TA, Kim SP, et al. Delays in diagnosis and bladder cancer mortality. Cancer. 2010;116(22):5235–42.PubMedCrossRefGoogle Scholar
  33. 33.
    McCombie SP, Bangash HK, Kuan M, Thyer I, Lee F, Hayne D. Delays in the diagnosis and initial treatment of bladder cancer in Western Australia. BJU Int. 2017;120(Suppl 3):28–34.PubMedCrossRefGoogle Scholar
  34. 34.
    Lotan Y, Svatek RS, Malats N. Screening for bladder cancer: a perspective. World J Urol. 2008;26(1):13–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Larré S, Catto JWF, Cookson MS, Messing EM, Shariat SF, Soloway MS, et al. Screening for bladder cancer: rationale, limitations, whom to target, and perspectives. Eur Urol. 2013;63(6):1049–58.PubMedCrossRefGoogle Scholar
  36. 36.
    Steiner H, Bergmeister M, Verdorfer I, Granig T, Mikuz G, Bartsch G, et al. Early results of bladder-cancer screening in a high-risk population of heavy smokers. BJU Int. 2008;102(3):291–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Starke N, Singla N, Haddad A, Lotan Y. Long-term outcomes in a high-risk bladder cancer screening cohort. BJU Int. 2015;117(4):611–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Lotan Y, Elias K, Svatek RS, Bagrodia A, Nuss G, Moran B, et al. Bladder cancer screening in a high risk asymptomatic population using a point of care urine based protein tumor marker. J Urol. 2009;182(1):52–7; discussion 58.PubMedCrossRefGoogle Scholar
  39. 39.
    Zlotta AR, Roumeguere T, Kuk C, Alkhateeb S, Rorive S, Lemy A, et al. Select screening in a specific high-risk population of patients suggests a stage migration toward detection of non-muscle-invasive bladder cancer. Eur Urol. 2011;59(6):1026–31.PubMedCrossRefGoogle Scholar
  40. 40.
    Messing EM, Madeb R, Young T, Gilchrist KW, Bram L, Greenberg EB, et al. Long-term outcome of hematuria home screening for bladder cancer in men. Cancer. 2006;107(9):2173–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Hedelin H, Jonsson K, Salomonsson K, Boman H. Screening for bladder tumours in men aged 60-70 years with a bladder tumour marker (UBC) and dipstick-detected haematuria using both white-light and fluorescence cystoscopy. Scand J Urol Nephrol. 2006;40(1):26–30.PubMedCrossRefGoogle Scholar
  42. 42.
    Roobol MJ, Bangma CH, el Bouazzaoui S, Franken-Raab CG, Zwarthoff EC. Feasibility study of screening for bladder cancer with urinary molecular markers (the BLU-P project). Urol Oncol. 2010;28(6):686–90.PubMedCrossRefGoogle Scholar
  43. 43.
    Bangma CH, Loeb S, Busstra M, Zhu X, El Bouazzaoui S, Refos J, et al. Outcomes of a bladder cancer screening program using home hematuria testing and molecular markers. Eur Urol. 2013;64(1):41–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Giberti C, Gallo F, Schenone M, Genova A. Early results of urothelial carcinoma screening in a risk population of coke workers: urothelial carcinoma among coke workers. Biomed Environ Sci. 2010;23(4):300–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Pesch B, Nasterlack M, Eberle F, Bonberg N, Taeger D, Leng G, et al. The role of haematuria in bladder cancer screening among men with former occupational exposure to aromatic amines. BJU Int. 2011;108(4):546–52.PubMedCrossRefGoogle Scholar
  46. 46.
    Huber S, Schwentner C, Taeger D, Pesch B, Nasterlack M, Leng G, et al. Nuclear matrix protein-22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study. BJU Int. 2012;110(5):699–708.PubMedCrossRefGoogle Scholar
  47. 47.
    Taiwo OA, Slade MD, Cantley LF, Tessier-Sherman B, Galusha D, Kirsche SR, et al. Bladder cancer screening in aluminum smelter workers. J Occup Environ Med. 2015;57(4):421–7.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Lotan Y, Kamat AM, Porter MP, Robinson VL, Shore N, Jewett M, et al. Key concerns about the current state of bladder cancer: a position paper from the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology. Cancer. 2009;115(18):4096–103.PubMedCrossRefGoogle Scholar
  49. 49.
    Lotan Y, Roehrborn CG. Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses. Urology. 2003;61(1):109–18. discussion 118.PubMedCrossRefGoogle Scholar
  50. 50.
    Bastacky S, Ibrahim S, Wilczynski SP, Murphy WM. The accuracy of urinary cytology in daily practice. Cancer. 1999;87(3):118–28.PubMedCrossRefGoogle Scholar
  51. 51.
    Babjuk M, Bohle A, Burger M, Comperat E, Kaasinen E, Palou J, et al. Guidelines on non-muscle-invasive bladder cancer (Ta, T1 and CIS). In: EAU guidelines: European Association of Urology; 2015.Google Scholar
  52. 52.
    Bellmunt J, Orsola A, Leow JJ, Wiegel T, De Santis M, Horwich A, et al. Bladder cancer: ESMO practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii40–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Klatte T, Shariat SF. Novel urinary markers for detection of bladder cancer-are we failing? J Urol. 2014;191(1):9–10.PubMedCrossRefGoogle Scholar
  54. 54.
    Bensalah K, Montorsi F, Shariat SF. Challenges of cancer biomarker profiling. Eur Urol. 2007;52(6):1601–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Lotan Y, Svatek RS, Krabbe L-M, Xylinas E, Klatte T, Shariat SF. Prospective external validation of a bladder cancer detection model. J Urol. 2014;192(5):1343–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Böhle A, Jocham D, Bock PR. Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity. J Urol. 2003;169(1):90–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Han RF, Pan JG. Can intravesical bacillus Calmette-Guérin reduce recurrence in patients with superficial bladder cancer? A meta-analysis of randomized trials. Urology. 2006;67(6):1216–23.PubMedCrossRefGoogle Scholar
  58. 58.
    Shelley MD, Kynaston H, Court J, Wilt TJ, Coles B, Burgon K, et al. A systematic review of intravesical bacillus Calmette-Guérin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer. BJU Int. 2001;88(3):209–16.PubMedCrossRefGoogle Scholar
  59. 59.
    Shelley MD, Wilt TJ, Court J, Coles B, Kynaston H, Mason MD. Intravesical bacillus Calmette-Guérin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials. BJU Int. 2004;93(4):485–90.PubMedCrossRefGoogle Scholar
  60. 60.
    Malmström P-U, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer. Eur Urol. 2009;56(2):247–56.PubMedCrossRefGoogle Scholar
  61. 61.
    Spencer BA, McBride RB, Hershman DL, Buono D, Herr HW, Benson MC, et al. Adjuvant intravesical bacillus calmette-guérin therapy and survival among elderly patients with non-muscle-invasive bladder cancer. J Oncol Pract. 2013;9(2):92–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017;71(3):447–61.PubMedCrossRefGoogle Scholar
  63. 63.
    Rentsch CA, Birkhäuser FD, Biot C, Gsponer JR, Bisiaux A, Wetterauer C, et al. Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy. Eur Urol. 2014;66(4):677–88.PubMedCrossRefGoogle Scholar
  64. 64.
    Witjes JA, Dalbagni G, Karnes RJ, Shariat S, Joniau S, Palou J, et al. The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer. Urol Oncol. 2016;34(11):484.e19–25.CrossRefGoogle Scholar
  65. 65.
    Guerrero-Ramos F, Lara-Isla A, Justo-Quintas J, Duarte-Ojeda JM, de la Rosa-Kehrmann F, Villacampa-Aubá F. Adjuvant intravesical treatment for nonmuscle invasive bladder cancer: the importance of the strain and maintenance. Actas Urol Esp. 2017;41(9):590–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Sengiku A, Ito M, Miyazaki Y, Sawazaki H, Takahashi T, Ogura K. A prospective comparative study of intravesical bacillus Calmette-Guérin therapy with the Tokyo or Connaught strain for nonmuscle invasive bladder cancer. J Urol. 2013;190(1):50–4.PubMedCrossRefGoogle Scholar
  67. 67.
    Boehm BE, Cornell JE, Wang H, Mukherjee N, Oppenheimer JS, Svatek RS. Efficacy of bacillus Calmette-Guérin strains for treatment of nonmuscle invasive bladder cancer: a systematic review and network meta-analysis. J Urol. 2017;198(3):503–10.PubMedCrossRefGoogle Scholar
  68. 68.
    Steinberg RL, Brooks NA, Thomas LJ, Mott SL, O’Donnell MA. Bacillus Calmette-Guerin strain may not effect recurrence-free survival when used intravesically with interferon-alpha2b for non-muscle-invasive bladder cancer. Urol Oncol. 2017;35(5):201–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Steinberg RL, Thomas LJ, Nepple KG. Intravesical and alternative bladder-preservation therapies in the management of non-muscle-invasive bladder cancer unresponsive to bacillus Calmette-Guérin. Urol Oncol. 2016;34(6):279–89.PubMedCrossRefGoogle Scholar
  70. 70.
    Gual Frau J, Palou J, Rodríguez O, Parada R, Breda A, Villavicencio H. Failure of Bacillus Calmette-Guérin therapy in non-muscle-invasive bladder cancer: definition and treatment options. Arch Esp Urol. 2016;69(7):423–33.PubMedGoogle Scholar
  71. 71.
    Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol. 2000;163(3):761–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Dinney CPN, Greenberg RE, Steinberg GD. Intravesical valrubicin in patients with bladder carcinoma in situ and contraindication to or failure after bacillus Calmette-Guérin. Urol Oncol. 2013;31(8):1635–42.PubMedCrossRefGoogle Scholar
  73. 73.
    Morales A, Phadke K, Steinhoff G. Intravesical mycobacterial cell wall-DNA complex in the treatment of carcinoma in situ of the bladder after standard intravesical therapy has failed. J Urol. 2009;181(3):1040–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Morales A, Herr H, Steinberg G, Given R, Cohen Z, Amrhein J, et al. Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin. J Urol. 2015;193(4):1135–43.PubMedCrossRefGoogle Scholar
  75. 75.
    Dalbagni G, Russo P, Bochner B, Ben-Porat L, Sheinfeld J, Sogani P, et al. Phase II trial of intravesical gemcitabine in bacille Calmette-Guérin-refractory transitional cell carcinoma of the bladder. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(18):2729–34.CrossRefGoogle Scholar
  76. 76.
    Skinner EC, Goldman B, Sakr WA, Petrylak DP, Lenz H-J, Lee CT, et al. SWOG S0353: phase II trial of intravesical gemcitabine in patients with nonmuscle invasive bladder cancer and recurrence after 2 prior courses of intravesical bacillus Calmette-Guérin. J Urol. 2013;190(4):1200–4.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Di Lorenzo G, Perdonà S, Damiano R, Faiella A, Cantiello F, Pignata S, et al. Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial. Cancer. 2010;116(8):1893–900.PubMedCrossRefGoogle Scholar
  78. 78.
    Lightfoot AJ, Breyer BN, Rosevear HM, Erickson BA, Konety BR, O’Donnell MA. Multi-institutional analysis of sequential intravesical gemcitabine and mitomycin C chemotherapy for non-muscle invasive bladder cancer. Urol Oncol. 2014;32(1):35.e15–9.CrossRefGoogle Scholar
  79. 79.
    Steinberg RL, Thomas LJ, O’Donnell MA, Nepple KG. Sequential Intravesical gemcitabine and docetaxel for the salvage treatment of non-muscle invasive bladder cancer. Bl Cancer. 2015;1(1):65–72.CrossRefGoogle Scholar
  80. 80.
    McKiernan JM, Masson P, Murphy AM, Goetzl M, Olsson CA, Petrylak DP, et al. Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(19):3075–80.CrossRefGoogle Scholar
  81. 81.
    Barlow LJ, McKiernan JM, Benson MC. Long-term survival outcomes with intravesical docetaxel for recurrent nonmuscle invasive bladder cancer after previous bacillus Calmette-Guérin therapy. J Urol. 2013;189(3):834–9.PubMedCrossRefGoogle Scholar
  82. 82.
    McKiernan JM, Holder DD, Ghandour RA, Barlow LJ, Ahn JJ, Kates M, et al. Phase II trial of intravesical nanoparticle albumin bound paclitaxel for the treatment of nonmuscle invasive urothelial carcinoma of the bladder after bacillus Calmette-Guérin treatment failure. J Urol. 2014;192(6):1633–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Robins DJ, Sui W, Matulay JT, Ghandour R, Anderson CB, DeCastro GJ, et al. Long-term survival outcomes with intravesical nanoparticle albumin-bound paclitaxel for recurrent non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin therapy. Urology. 2017;103:149–53.PubMedCrossRefGoogle Scholar
  84. 84.
    Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;342(6165):1432–3.PubMedCrossRefGoogle Scholar
  85. 85.
    Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Rezvani K, Rouce R, Liu E, Shpall E. Engineering natural killer cells for cancer immunotherapy. Mol Ther. 2017;25(8):1769–81.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–3.PubMedCrossRefGoogle Scholar
  88. 88.
    Redelman-Sidi G, Glickman MS, Bochner BH. The mechanism of action of BCG therapy for bladder cancer—a current perspective. Nat Rev Urol. 2014;11(3):153–62.PubMedCrossRefGoogle Scholar
  89. 89.
    Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet Lond Engl. 2017;389(10064):67–76.CrossRefGoogle Scholar
  90. 90.
    Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. 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 Lond Engl. 2016;387(10031):1909–20.CrossRefGoogle Scholar
  91. 91.
    Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(26):3119–25.CrossRefGoogle Scholar
  92. 92.
    Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K, et al. 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 Off J Am Soc Clin Oncol. 2017;35(19):2117–24.CrossRefGoogle Scholar
  93. 93.
    Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312–22.PubMedCrossRefGoogle Scholar
  94. 94.
    Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–26.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Meng X, Huang Z, Teng F, Xing L, Yu J. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41(10):868–76.PubMedCrossRefGoogle Scholar
  96. 96.
    Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F, et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol. 2016;27(4):559–74.PubMedCrossRefGoogle Scholar
  97. 97.
    Ascierto PA, Del Vecchio M, Robert C, Mackiewicz A, Chiarion-Sileni V, Arance A, et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2017;18(5):611–22.PubMedCrossRefGoogle Scholar
  98. 98.
    Maruf M, Brancato SJ, Agarwal PK. Nonmuscle invasive bladder cancer: a primer on immunotherapy. Cancer Biol Med. 2016;13(2):194–205.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Mihai Dorin Vartolomei
    • 1
    • 2
  • Shahrokh F. Shariat
    • 1
    • 3
    • 4
    • 5
    Email author
  1. 1.Department of UrologyMedical University of ViennaViennaAustria
  2. 2.Department of Cell and Molecular BiologyUniversity of Medicine and PharmacyTirgu MuresRomania
  3. 3.Karl Landsteiner Institute of Urology and AndrologyViennaAustria
  4. 4.Department of UrologyUniversity of Texas Southwestern Medical CenterDallasUSA
  5. 5.Department of UrologyWeill Cornell Medical CollegeNew YorkUSA

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