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Neoadjuvant chemotherapy for bladder cancer

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Abstract

The 30–45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both—treatment-related toxicity and the inability to prospectively identify likely responders—are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

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References

  1. Abol-Enein HE-MM, El-Baz M, Ghoneim MA (1997) Neo-adjuvant chemotherapy in the treatment of invasive transitional bladder cancer. BJU Int 79(suppl 4):174

    Google Scholar 

  2. Arnoletti JP, Bland KI (2006) Neoadjuvant and adjuvant therapy for rectal cancer. Surg Oncol Clin N Am 15(1):147–157

    PubMed  Google Scholar 

  3. Bassi P, Ferrante GD, Piazza N, Spinadin R, Carando R, Pappagallo G et al (1999) Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort. J Urol 161(5):1494–1497

    Article  PubMed  CAS  Google Scholar 

  4. Bassi P, Pappagallo GL, Sperandio P, Monfardini S, Pagano F, Cosciani S et al (1999) Neoadjuvant M-VAC chemotherapy of invasive bladder cancer: results of a multicenter phase III trial. J Urol 161(suppl):264

    Article  Google Scholar 

  5. Bex A, Nieuwenhuijzen JA, Kerst M, Pos F, van Boven H, Meinhardt W et al (2005) Small cell carcinoma of bladder: a single-center prospective study of 25 cases treated in analogy to small cell lung cancer. Urology 65(2):295–299

    Article  PubMed  Google Scholar 

  6. Cannobio L, Curotto A, Boccardo F, Venturini M, Orsatti M, Vitale V et al (1995) A randomized study between neo-adjuvant chemoradiotherapy (CT-RT) before radical cystectomy and cystectomy alone in bladder cancer. A 6 year follow-up. Proc Am Soc Clin Oncol 14:245

    Google Scholar 

  7. Carlini LE, Meropol NJ, Bever J, Andria ML, Hill T, Gold P et al (2005) UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res 11(3):1226–1236

    PubMed  CAS  Google Scholar 

  8. Chung D, Hersey K, Fleshner N (2005) Differences between urologists in United States and Canada in approach to bladder cancer. Urology 65(5):919–925

    Article  PubMed  Google Scholar 

  9. Cote RJ, Esrig D, Groshen S, Jones PA, Skinner DG (1997) p53 and treatment of bladder cancer. Nature 385(6612):123–125

    Article  PubMed  CAS  Google Scholar 

  10. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJH, Nicolson M et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20

    Article  PubMed  CAS  Google Scholar 

  11. Dalbagni G, Genega E, Hashibe M, Zhang ZF, Russo P, Herr H et al (2001) Cystectomy for bladder cancer: a contemporary series. J Urol 165(4):1111–1116

    Article  PubMed  CAS  Google Scholar 

  12. Donat SM, Genega EM, Herr HW, Reuter VE (2001) Mechanisms of prostatic stromal invasion in patients with bladder cancer: clinical significance. J Urol 165(4):1117–1120

    Article  PubMed  CAS  Google Scholar 

  13. Feneley MR, Harland S (2003) Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a new standard of care? BJU Int 92(9):877–878

    Article  PubMed  CAS  Google Scholar 

  14. Flanigan RC (2004) Debulking nephrectomy in metastatic renal cancer. Clin Cancer Res 10(18):6335S–6341S

    Article  PubMed  Google Scholar 

  15. Font A, Abad A, Saladie JM, Carles J, Pinsach L, Barnardas A et al (1994) Improved survival with induction chemotherapy in bladder cancer: preliminary results of a randomized trial. Ann Oncol 5:71

    Google Scholar 

  16. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL et al (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349(9):859–866

    Article  PubMed  CAS  Google Scholar 

  17. Haleblian GE, Skinner EC, Dickinson MG, Lieskovsky G, Boyd SD, Skinner DG (1998) Hydronephrosis as a prognostic indicator in bladder cancer patients. J Urol 160(6):2011–2014

    Article  PubMed  CAS  Google Scholar 

  18. Hall MC, Swanson DA, Dinney CP (1996) Complications of radical cystectomy: impact of the timing of perioperative chemotherapy. Urology 47(6):826–830

    Article  PubMed  CAS  Google Scholar 

  19. Hall RR (2002) Updated results of a randomised controlled trial of neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy for muscle invasive bladder cancer. Proc Am Soc Clin Oncol 21:178

    Google Scholar 

  20. Han J-Y, Lim H-S, Shin ES, Yoo Y-K, Park YH, Lee J-E et al (2006) Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol 24(15):2237–2244

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Herr HW, Donat SM (2001) Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy. J Urol 165(1):62–64

    Article  PubMed  CAS  Google Scholar 

  23. Herr HW, Faulkner JR, Grossman HB, Natale RB, deVere White R, Sarosdy MF et al (2004) Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol 22(14):2781–2789

    Article  PubMed  Google Scholar 

  24. Inoue K, Slaton JW, Karashima T, Yoshikawa C, Shuin T, Sweeney P et al (2000) The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy. Clin Cancer Res 6(12):4866–4873

    PubMed  CAS  Google Scholar 

  25. Kachnic LA, Kaufman DS, Heney NM, Althausen AF, Griffin PP, Zietman AL et al (1997) Bladder preservation by combined modality therapy for invasive bladder cancer. J Clin Oncol 15(3):1022–1029

    PubMed  CAS  Google Scholar 

  26. Kamat AM, Gee JR, Dinney CP, Grossman HB, Swanson DA, Millikan RE et al (2006) The case for early cystectomy in the treatment of nonmuscle invasive micropapillary bladder carcinoma. J Urol 175(3):881–885

    Article  PubMed  Google Scholar 

  27. Konety BR, Joslyn SA (2003) Factors influencing aggressive therapy for bladder cancer: an analysis of data from the SEER program. J Urol 170(5):1765–1771

    Article  PubMed  Google Scholar 

  28. Lee CT, Madii R, Daignault S, Dunn RL, Zhang Y, Montie JE et al (2006) Cystectomy delay more than 3 months from initial bladder cancer diagnosis results in decreased disease specific and overall survival. J Urol 175(4):1262–1267

    Article  PubMed  Google Scholar 

  29. Lopez-Beltran A, Pacelli A, Rothenberg HJ, Wollan PC, Zincke H, Blute ML et al (1998) Carcinosarcoma and sarcomatoid carcinoma of the bladder: clinicopathological study of 41 cases. J Urol 159(5):1497–1503

    Article  PubMed  CAS  Google Scholar 

  30. Madersbacher S, Hochreiter W, Burkhard F, Thalmann GN, Danuser H, Markwalder R et al (2003) Radical cystectomy for bladder cancer today—a homogeneous series without neoadjuvant therapy. J Clin Oncol 21(4):690–696

    Article  PubMed  Google Scholar 

  31. Maitland ML, DiRienzo A, Ratain MJ (2006) Interpreting disparate responses to cancer therapy: the role of human population genetics. J Clin Oncol 24(14):2151–2157

    Article  PubMed  Google Scholar 

  32. Malmstrom PU, Rintala E, Wahlqvist R, Hellstrom P, Hellsten S, Hannisdal E (1996) Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group. J Urol 155(6):1903–1906

    Article  PubMed  CAS  Google Scholar 

  33. Maranchie JK, Bouyounes BT, Zhang PL, O’Donnell MA, Summerhayes IC, DeWolf WC (2000) Clinical and pathological characteristics of micropapillary transitional cell carcinoma: a highly aggressive variant. J Urol 163(3):748–751

    Article  PubMed  CAS  Google Scholar 

  34. Marsh S, McLeod HL (2006) Pharmacogenomics: from bedside to clinical practice. Hum Mol Genet 15(1):R89–R93

    Article  PubMed  CAS  Google Scholar 

  35. Millikan R, Dinney C, Swanson D, Sweeney P, Ro JY, Smith TL et al (2001) Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. J Clin Oncol 19(20):4005–4013

    PubMed  CAS  Google Scholar 

  36. Millikan R, Siefker-Radtke A, Grossman HB (2003) Neoadjuvant chemotherapy for bladder cancer. Urol Oncol 21(6):464–467

    PubMed  Google Scholar 

  37. Natale RB, Grossman HB, Blumenstein B, Vogelzang NJ, Trump DL, Speights VO (2001) SWOG 8710 (INT-0080): randomized phase III trial of neoadjuvant MVAC+ cystectomy versus cystectomy alone in patients with locally advanced bladder cancer [abstract]. Proc Am Soc Clin Oncol 20:2a

    Google Scholar 

  38. Neoadjuvant chemotherapy for invasive bladder cancer (2005) Cochrane Database Syst Rev (2):CD005246

  39. Advanced Bladder Cancer (2003) (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 361(9373):1927–1934

    Google Scholar 

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

    Google Scholar 

  41. International Collaboration of Trialists (1999) Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet 354(9178):533–540

    Google Scholar 

  42. Italian Bladder Cancer Study Group (1996) Neoadjuvant treatment for locally advanced bladder cancer: a randomized prospective clinical trial. J Chemother 8(suppl):345

    Google Scholar 

  43. Nieuwenhuijzen JA, Bex A, Meinhardt W, Kerst JM, Schornagel JH, Vant H et al (2005) Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for histologically proven lymph node positive bladder cancer. J Urol 174(1):80–85

    Article  PubMed  CAS  Google Scholar 

  44. Prout GR Jr, Griffin PP, Shipley WU (1979) Bladder carcinoma as a systemic disease. Cancer 43(6):2532–2539

    Article  PubMed  Google Scholar 

  45. RR H (2002) Updated results of a randomised controlled trial of neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy for muscle invasive bladder cancer. Proc Am Soc Clin Oncol 21:178

    Google Scholar 

  46. Sanchez-Ortiz RF, Huang WC, Mick R, Van Arsdalen KN, Wein AJ, Malkowicz SB (2003) An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol 169(1):110–115

    Article  PubMed  Google Scholar 

  47. Sarkis AS, Bajorin DF, Reuter VE, Herr HW, Netto G, Zhang ZF et al (1995) Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC. J Clin Oncol 13(6):1384–1390

    PubMed  CAS  Google Scholar 

  48. Schrag D, Mitra N, Xu F, Rabbani F, Bach PB, Herr H et al (2005) Cystectomy for muscle-invasive bladder cancer: patterns and outcomes of care in the Medicare population. Urology 65(6):1118–1125

    Article  PubMed  Google Scholar 

  49. Schultz PK, Herr HW, Zhang ZF, Bajorin DF, Seidman A, Sarkis A et al (1994) Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up. J Clin Oncol 12(7):1394–1401

    PubMed  CAS  Google Scholar 

  50. Sengelov L, von der Maase H, Lundbeck F, Barlebo H, Colstrup H, Engelholm SA et al (2002) Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours. Acta Oncol 41(5):447–456

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  52. Sherif A, Rintala E, Mestad O, Nilsson J, Holmberg L, Nilsson S et al (2002) Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer—Nordic cystectomy trial 2. Scand J Urol Nephrol 36(6):419–425

    Article  PubMed  CAS  Google Scholar 

  53. Shipley WU, Kaufman DS, Tester WJ, Pilepich MV, Sandler HM (2003) Overview of bladder cancer trials in the Radiation Therapy Oncology Group. Cancer 97(8):2115–2119

    Article  PubMed  CAS  Google Scholar 

  54. Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR et al (1998) Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89–03. J Clin Oncol 16(11):3576–3583

    PubMed  CAS  Google Scholar 

  55. Shokeir AA (2004) Squamous cell carcinoma of the bladder: pathology, diagnosis and treatment. BJU Int 93(2):216–220

    Article  PubMed  CAS  Google Scholar 

  56. Siefker-Radtke A (2006) Systemic chemotherapy options for metastatic bladder cancer. Expert Rev Anticancer Ther 6(6):877–885

    Article  PubMed  CAS  Google Scholar 

  57. Siefker-Radtke AO, Dinney CP, Abrahams NA, Moran C, Shen Y, Pisters LL et al (2004) Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: a retrospective review of the M. D. Anderson cancer experience. J Urol 172(2):481–484

    Article  PubMed  Google Scholar 

  58. Siefker-Radtke AO, Thall PF, Tannir NM, Tu SM, Pagliaro LC, Williams DL et al (2004) Implementation of a novel statistical design to evaluate successive treatment courses for metastatic transitional cell carcinoma. A Phase II trial at the M. D. Anderson Cancer Center. J Clin Oncol 22(14):4543

    Google Scholar 

  59. Slaton JW, Millikan R, Inoue K, Karashima T, Czerniak B, Shen Y 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(2 Pt 1):570–574

    Article  PubMed  CAS  Google Scholar 

  60. Smith I, Chua S (2006) Medical treatment of early breast cancer. IV: neoadjuvant treatment. BMJ 332(7535):223–224

    Article  PubMed  Google Scholar 

  61. Snyder C, Harlan L, Knopf K, Potosky A, Kaplan R (2003) Patterns of care for the treatment of bladder cancer. J Urol 169(5):1697–1701

    Article  PubMed  Google Scholar 

  62. Sonpavde G, Petrylak DP (2006) Perioperative chemotherapy for bladder cancer. Crit Rev Oncol Hematol 57(2):133–144

    PubMed  Google Scholar 

  63. Splinter TA, Pavone-Macaluso M, Jacqmin D, Roberts JT, Carpentier P, de Pauw M et al (1992) A European Organization for Research and Treatment of Cancer–Genitourinary Group phase 2 study of chemotherapy in stage T3–4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response. J Urol 148(6):1793–1796

    PubMed  CAS  Google Scholar 

  64. Splinter TA, Scher HI, Denis L, Bukowski R, Simon S, Klimberg I et al (1992) The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. European Organization for Research on Treatment of Cancer–Genitourinary Group. J Urol 147(3):606–608

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  66. Sternberg CN, de Mulder PH, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT et al (2001) 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 19(10):2638–2646

    PubMed  CAS  Google Scholar 

  67. Sternberg CN, Pansadoro V, Calabro F, Schnetzer S, Giannarelli D, Emiliozzi P et al (2003) Can patient selection for bladder preservation be based on response to chemotherapy? Cancer 97(7):1644–1652

    Article  PubMed  Google Scholar 

  68. Sternberg CN, Parmar MK (2001) Neoadjuvant chemotherapy is not (yet) standard treatment for muscle-invasive bladder cancer. J Clin Oncol 19(18 Suppl):21S–26S

    PubMed  CAS  Google Scholar 

  69. Sternberg CN, Yagoda A, Scher HI, Watson RC, Ahmed T, Weiselberg LR et al (1985) Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. J Urol 133(3):403–407

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  71. Vieweg J, Gschwend JE, Herr HW, Fair WR (1999) Pelvic lymph node dissection can be curative in patients with node positive bladder cancer. J Urol 161(2):449–454

    Article  PubMed  CAS  Google Scholar 

  72. von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ et al (2000) 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 18(17):3068–3077

    PubMed  Google Scholar 

  73. Winquist E, Kirchner TS, Segal R, Chin J, Lukka H (2004) Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 171(2):561–569

    Article  PubMed  CAS  Google Scholar 

  74. Winquist E, Waldron T, Segal R, Chin J, Lukka H et al (2005) Use of neoadjuvant chemotherapy in transitional cell carcinoma of the bladder. Practice guideline report #3–2–2 (Version 2.2005), May 5

  75. Wu X, Gu J, Grossman HB, Amos CI, Etzel C, Huang M et al (2006) Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet 78(3):464–479

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Colin P. Dinney.

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Black, P.C., Brown, G.A., Grossman, H.B. et al. Neoadjuvant chemotherapy for bladder cancer. World J Urol 24, 531–542 (2006). https://doi.org/10.1007/s00345-006-0113-z

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