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Treatment of muscle-invasive and metastatic bladder cancer – update of the EAU Guidelines


Authors: A. Stenzl 1;  N. C. Cowan 2;  M. De Santis 3;  M. A. Kuczyk 4;  A. S. Merseburger 4;  M. J. Ribal 5;  A. Sherif 6;  J. A. Witjes 7
Authors‘ workplace: Department of Urology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 7 07 Tuebingen, Germany 1;  Department of Radiology, The Churchill Hospital, Oxford, United Kingdom 2;  3rd Medical Department and ACR-ITR/CEADDP and LBI-ACR Vienna-CTO, Kaiser Franz Josef Spital, Vienna, Austria 3;  Department of Urology and Urologic Oncology, Hannover Medical School (MHH), Hannover, Germany 4;  Department of Urology, Hospital Clinic, University of Barcelona, Barcelona, Spain 5;  Department of Urology, Karolinska University Hospital, Stockholm, Sweden 6;  Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 7
Published in: Urol List 2011; 9(3): 75-86

Overview

Context:
New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC.

Objective:
To review the new EAU guidelines for MiM-BC with a specific focus on treatment.

Evidence acquisition:
New literature published since the last update of the EAU Guidelines in 2008 was obtained from Medline, the Cochrane Database of Syste­matic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence.

Evidence synthesis:
Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomyis not considered formedical or personal reasons. Inmetastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available.

Conclusions:
In the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be con­sidered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.

Key words:
bladder cancer, muscle-invasive, chemotherapy, radiation therapy, cystectomy, EAU Guidelines, multidisciplinary management, quality of life


Sources

1. Oxford Centre for Evidence-based Medicine – levels of evidence (March 2009). Centre for Evidence-based Medicine Web site. http://www.cebm.net/index. aspx?o=1025. Updated March 2009.

2. Sternberg CN, Pansadoro V, Calabro F et al. Can patient selection for bladder preservation be based on response to chemotherapy? Cancer 2003; 97(7): 1644–1652.

3. Sanchez-Ortiz RF, Huang WC, Mick R et al. An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol 2003; 169(1): 110–115.

4. Stein JP. Contemporary concepts of radical cystectomy and the treatment of bladder cancer. J Urol 2003; 169(1): 116–117.

5. Grossman HB, Natale RB, Tangen CM et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003; 349(9): 859–866.

6. Sherif A, Holmberg L, Rintala E et al. Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies. Eur Urol 2004; 45(3): 297–303.

7. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data. Eur Urol 2005; 48(2): 189–201.

8. Herr HW, Bajorin DF, Scher HI. Neoadjuvant che­mo­therapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome. J Clin Oncol 1998; 16(4): 1298–1301.

9. Widmark A, Flodgren P, Damber JE et al. A systematic overview of radiation therapy effects in urinary bladder cancer. Acta Oncol 2003; 42(5–6): 567–581.

10. Granfors T, Tomic R, Ljungberg B. Downstaging and survival benefits of neoadjuvant radiotherapy before cystectomy for patients with invasive bladder carcinoma. Scand J Urol Nephrol 2009; 43(4): 293–299.

11. Rödel C, Weiss C, Sauder R. Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol 2006; 24(35): 5536–5544.

12. Hautmann RE, Abol-Enein H, Hafez K et al. Urinary diversion, WHO Consensus Conference on Bladder Cancer. Urology 2007; 69 (Suppl 1): 17–49.

13. Stenzl A, Nagele U, Kuczyk M et al. Cystectomy – technical considerations in male and female patients. EAU Update Series 2005; 3: 138–146.

14. Abdelhady M, Abusamra A, Pautler SE et al. Cli­ni­cally significant prostate cancer found incidentally in radical cystoprostatectomy specimens. BJU Int 2007; 99(2): 326–329.

15. Pettus JA, Al-Ahmadie H, Barocas DA et al. Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy. Eur Urol 2008; 53(2): 370–375.

16. Weizer AZ, Shah RB, Lee CT et al. Evaluation of the prostate peripheral zone/capsule in patients undergoing radical cystoprostatectomy: defining risk with prostate capsule sparing cystectomy. Urol Oncol 2007; 25(6): 460–464.

17. Gakis G, Schilling D, Bedke J et al. Incidental prostate cancer at radical cystoprostatectomy: implications for apex-sparing surgery. BJU Int 2010; 105(4): 468–471.

18. Ong CH, Schmitt M, Thalmann GN et al. Indi­vidualized seminal vesicle sparing cystoprostatec­tomy combined with ileal orthotopic bladder substitution achieves good functional results. J Urol 2010; 183(4): 1337–1341.

19. Colombo R, Hautmann RE. Open to debate. The motion: seminal-nerve sparing radical cystectomy is an efficacious and safe treatment for selected bladder cancer patients. Eur Urol 2008; 53(1): 203–207.

20. Stenzl A, Colleselli K, Poisel S et al. Rationale and technique of nerve sparing radical cystectomy before an orthotopic neobladder procedure in women. J Urol 1995; 154(6): 2044–2049.

21. Gakis G, Schilling D, Perner S et al. Sequential resection of malignant ureteral margins at radical cystectomy: a critical assessment of the value of frozen section analysis. World J Urol 2011; 29(4): 451–456.

22. Tollefson MK, Blute ML, Farmer SA et al. Sig­nificance of distal ureteral margin at radical cystectomy for urothelial carcinoma. J Urol 2010; 183(1): 81–86.

23. Schumacher MC, Scholz M, Weise ES et al. Is there an indication for frozen section examination of the ureteral margins during cystectomy for transitio­nal cell carcinoma of the bladder? J Urol 2006; 176 (6 Pt 1): 2409–2413.

24. Herr HW, Bochner BH, Dalbagni G et al. Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol 2002; 167(3): 1295–1298.

25. Leissner J, Hohenfellner R, Thuroff JW et al. Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis. BJU Int 2000; 85(7): 817–823.

26. Poulsen AL, Horn T, Steven K. Radical cystectomy: extending the limits of pelvic lymph node dissection improves survival for patients with bladder cancer con­fined to the bladder wall. J Urol 1998; 160 (6 Pt 1): 2015–2019.

27. Ghoneim MA, Abol-Enein H. Lymphadenectomy with cystectomy: is it necessary and what is its extent? Eur Urol 2004; 46(4): 457–461.

28. Roth B, Wissmeyer MP, Zehnder P et al. A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. Eur Urol 2010; 57(2): 205–211.

29. Pruthi RS, Nix J, McRackan D et al. Robotic-assisted laparoscopic intracorporeal urinary diversion. Eur Urol 2010; 57(6): 1013–1021.

30. Hautmann RE. The oncologic results of laparoscopic radical cystectomy are not (yet) equivalent to open cystectomy. Curr Opin Urol 2009; 19(5): 522–526.

31. Haber GP, Crouzet S, Gill IS. Laparoscopic and robotic assisted radical cystectomy for bladder cancer: a critical analysis. Eur Urol 2008; 54(1): 54–64.

32. Gakis G, Stenzl A. Ileal neobladder and its variants. Eur Urol 2010; Suppl 9: 745–753.

33. Pycha A, Comploj E, Martini T et al. Comparison of complications in three incontinent urinary diversions. Eur Urol 2008; 54(4): 825–832.

34. Nieuwenhuijzen JA, de Vries RR, Bex A et al. Urinary diversions after cystectomy: the association of clinical factors, complications and functional results of four different diversions. Eur Urol 2008; 53(4): 834–844.

35. Farnham SB, Cookson MS. Surgical complications of urinary diversion. World J Urol 2004; 22(3): 157–167.

36. Stenzl A, Sherif H, Kuczyk M. Radical cystectomy with orthotopic neobladder for invasive bladder cancer: a critical analysis of long term oncological, functional and quality of life results. Int Braz J Urol 2010; 36(5): 537–547.

37. Stein JP, Clark P, Miranda G et al. Urethral tumor recurrence following cystectomy and urinary diversion: clinical and pathological characteristics in 768 male patients. J Urol 2005; 173(4): 1163–1168.

38. Hautmann RE, Volkmer BG, Schumacher MC et al. Long-term results of standard procedures in urology: the ileal neobladder. World J Urol 2006; 24(3): 305–314.

39. Froehner M, Brausi MA, Herr HW et al. Com­plications following radical cystectomy for bladder cancer in the elderly. Eur Urol 2009; 56(3): 443–454.

40. Gschwend JE, Dahm P, Fair WR. Disease specific survival as endpoint of outcome for bladder cancer patients following radical cystectomy. Eur Urol 2002; 41(4): 440–448.

41. Shariat SF, Karakiewicz PI, Palapattu GS et al. Nomograms provide improved accuracy for predicting survival after radical cystectomy. Clin Cancer Res 2006; 12(22): 6663–6676.

42. Zaak D, Burger M, Otto W et al. Predicting indivi­dual outcomes after radical cystectomy: an external validation of current nomograms. BJU Int 2010; 106(3): 342–348.

43. Stein JP, Lieskovsky G, Cote R et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001; 19(3): 666–675.

44. Madersbacher A, Hochreiter F, Burkhard F et al. Radical cystectomy for bladder cancer today—a homogeneous series without neoadjuvant therapy. J Clin Oncol 2003; 21(4): 690–696.

45. Hollenbeck BK, Miller DC, Taub D et al. Aggressive treatment for bladder cancer is associated with improved overall survival among patients 80 years old or older. Urology 2004; 64(2): 292–297.

46. Lodde M, Palermo S, Comploj E et al. Four years experience in bladder preserving management for muscle invasive bladder cancer. Eur Urol 2005; 47(6): 773–779.

47. Nagele U, Anastasiadis AG, Merseburger AS et al. The rationale for radical cystectomy as primary therapy for T4 bladder cancer. World J Urol 2007; 25(4): 401–405.

48. Lawrentschuk N, Colombo R, Hakenberg OW et al. Prevention and management of complications following radical cystectomy for bladder cancer. Eur Urol 2010; 57(6): 983–1001.

49. Konety BR, Dhawan V, Allareddy V et al. Association between volume and charges for most frequently performed ambulatory and nonambulatory surgery for bladder cancer. Is more cheaper? J Urol 2004; 172(3): 1056–1061.

50. Hautmann RE, de Petriconi RC, Volkmer BG. Lessons learned from 1,000 neobladders: the 90-day complication rate. J Urol 2010; 184(3): 990–994.

51. Shamim Khan M, Elhage O et al. Analysis of early complications of robotic-assisted radical cystectomy using a standardized reporting system. Urology 2011; 77(2): 357–362.

52. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240(2): 205–213.

53. Svatek RS, Fisher MB, Matin SF et al. Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria. J Urol 2010; 183(3): 929–934.

54. Donat SM. Standards for surgical complication reporting in urologic oncology: time for a change. Urology 2007; 69(2): 221–225.

55. Novara G, De Marco V, Aragona M et al. Complications and mortality after radical cystectomy for bladder transitional cell cancer. J Urol 2009; 182(3): 914–921.

56. De Neve W, Lybeert ML, Goor C et al. Radiotherapy for T2 and T3 carcinoma of the bladder: the influence of overall treatment time. Radiother Oncol 1995; 36(3): 183–188.

57. Mameghan H, Fisher R, Mameghan J et al. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder. Int J Radiat Oncol Biol Phys 1995; 31(2): 247–254.

58. Näslund I, Nilsson B, Littbrand B. Hyper­fractionated radiotherapy of bladder cancer. A ten-year follow-up of a randomized clinical trial. Acta Oncol 1994; 33(4): 397–402.

59. Tonoli S, Bertoni F, De Stefani A et al. Radical radiotherapy for bladder cancer: retrospective analysis of a series of 459 patients treated in an Italian institution. Clin Oncol (R Coll Radiol) 2006; 18(1): 52–59.

60. Shelley MD, Barber J, Wilt T et al. Surgery versus radiotherapy for muscle invasive bladder cancer. Cochrane Database Syst Rev 2002; (1): CD002079.

61. Piet AH, Hulshof MC, Pieters BR et al. Clinical results of a concomitant boost radiotherapy technique for muscle-invasive bladder cancer. Strahle­nt­her Onkol 2008; 184(6): 313–318.

62. Eisenberg MS, Dorin RP, Bartsch G et al. Early complications of cystectomy after high dose pelvic radiation. J Urol 2010; 184(6): 2264–2269.

63. Kachni LA, Kaufman DS, Heney NM et al. Bladder preservation by combined modality therapy for invasive bladder cancer. J Clin Oncol 1997; 15(3): 1022–1029.

64. Als AB, Sengelov L, von der Maase H. Long-term survival after gemcitabine and cisplatin in patients with locally advanced transitional cell carcinoma of the bladder: focus on supplementary treatment strategies. Eur Urol 2007; 52(2): 478–487.

65. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data. Eur Urol 2005; 48(2): 202–206.

66. Weight CJ, Garcia JA, Hansel DE et al. Lack of pathologic down-staging with neoadjuvant chemo­therapy for muscle-invasive urothelial carcinoma of the bladder: a contemporary series. Cancer 2009; 115(4): 792–799.

67. Loehrer PJ Sr., Einhorn LH, Elson PJ et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 1992; 10(7): 1066–1073.

68. Bajorin DF, Dodd PM, Mazumdar M et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol 1999; 17(10): 3173–3181.

69. Bellmunt J, Albanell J, Paz-Ares L et al. Pre­treatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer 2002; 95(4): 751–757.

70. Bajorin D. The phase III candidate: can we improve the science of selection? J Clin Oncol 2004; 22(2): 211–213.

71. Bellmunt J, Choueiri TK, Fougeray R et al. Prog­nostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens. J Clin Oncol 2010; 28(11): 1850–1855.

72. De Santis M, Bachner M. New developments in first- and second-line chemotherapy for transitional cell, squamous cell and adenocarcinoma of the bladder. Curr Opin Urol 2007; 17(5): 363–368.

73. Sternberg CN, Yagoda A, Scher HI et al. Metho­trexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothe­lium. Efficacy and patterns of response and relapse. Cancer 1989; 64(12): 2448–2458.

74. Sternberg CN, Yagoda A, Scher HI et al. M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium. J Urol 1988; 139(3): 461–469.

75. von der Maase H, Hansen SW, Roberts JT et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000; 18(17): 3068–3077.

76. von der Maase H, Sengelov L, Roberts JT et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005; 23(21): 4602–4608.

77. Sternberg CN, de Mulder PH, Schornagel JH et al. European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol 2001; 19(10): 2638–2646.

78. Sternberg CN, de Mulder P, Schornagel JH et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer 2006; 42(1): 50–54.

79. Milowsky MI, Nanus DM, Maluf FC et al. Final results of sequential doxorubicin plus gemcitabine and ifosfamide, paclitaxel, and cisplatin chemotherapy in patients with metastatic or locally advanced transitional cell carcinoma of the urothelium. J Clin Oncol 2009; 27(25): 4062–4067.

80. Hussain MH, MacVicar GR, Petrylak DP et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol 2007; 25(16): 2218–2224.

81. De Santis M, Bellmunt J, Mead G et al. Randomized phase II/III trial assessing gemcita­bine/carboplatin and methotrexate/carboplatin/ /vinblastine in patients with advanced urothelial cancer “unfit” for cisplatin-based chemotherapy: phase II—results of EORTC study 30986. J Clin Oncol 2009; 27(33): 5634–5639.

82. Culine S, Theodore C, De Santis M. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer 2006; 94(10): 1395–1401.

83. Bellmunt J, Theodore C, Demkov T et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009; 27(27): 4454–4461.

84. Youssef RF, Mitra AP, Bartsch G Jr. et al. Molecular targets and targeted therapies in bladder cancer management. World J Urol 2009; 27(1): 9–20.

85. Shariat SF, Youssef RF, Gupta A et al. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol 2010; 183(5): 1744–1750.

86. Song S, Wientjes MG, Gan Y et al. Fibroblast growth factors: an epigenetic mechanism of broad spectrum resistance to anticancer drugs. Proc Natl Acad Sci USA 2000; 97(15): 8658–8663.

87. Gomez-Roman JJ, Saenz P, Molina M et al. Fibro­blast growth factor receptor 3 is overexpressed in urinary tract carcinomas and modulates the neoplastic cell growth. Clin Cancer Res 2005; 11 (2 Pt 1): 459–465.

88. Ioachim E, Michael MC, Salmas M et al. Throm­bospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components. BMC Cancer 2006; 6: 140.

89. Gallagher DJ, Milowsky MI, Ishill N et al. Detection of circulating tumor cells in patients with urothelial cancer. Ann Oncol 2009; 20(2): 305–308.

90. Hoffmann AC, Wild P, Leicht C et al. MDR1 and ERCC1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia 2010; 12(8): 628–636.

91. Aapro M, Abrahamsson PA, Body JJ et al. Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol 2008; 19(3): 420–432.

92. Zaghloul MS, Boutrus R, El-Hossieny H et al. A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer. Int J Clin Oncol 2010; 15(4): 382–389.

93. Rosen LS, Gordon D, Tchekmedyian NS et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer 2004; 100(12): 2613–2621.

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