Integrating Perioperative Chemotherapy into the Treatment of Muscle-Invasive Bladder Cancer: Strategy Versus Reality

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S. Machele DonatDivision of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York

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Since the initial report in 2003 of the Intergroup-0080 trial confirming benefit of combined neoadjuvant M-VAC (methotrexate, vinblastine, adriablastine, and cisplatin) chemotherapy and cystectomy in the treatment of muscle-invasive bladder cancer, debate has continued in the literature as to the relative risk/benefits of integrating perioperative chemotherapy into the care of patients, especially in those with organ-confined, muscle-invasive, node-negative disease in whom the benefit may be less. Because of the inaccuracies of clinical staging, the potential morbidity related to M-VAC chemotherapy, a 70% cure rate in pT2No disease with surgery alone, and only a modest (5%) improvement in absolute overall survival with combined therapy, many favor limiting chemotherapy to patients with a pathologic stage of pT3 or greater or node-positive disease. This philosophy was also reflected in the 2008 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Bladder Cancer, in which neoadjuvant chemotherapy for clinical T2 disease versus adjuvant therapy based on pathologic risks is only “considered.” Additionally, a recent study looking at the perioperative integration of chemotherapy for stage III bladder cancer in the United States using the National Cancer Data Base showed that only 11.6% of patients underwent any perioperative chemotherapy, with most in the adjuvant setting. These findings indicate that despite randomized trial data showing survival benefit for perioperative chemotherapy, and the current guidelines for therapy supporting those findings, chemotherapy is not being integrated well into the care of patients with muscle-invasive bladder cancer, even in those who, experts agree, have the most potential for benefit.

Correspondence: S. Machele Donat, MD, Department of Urology, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, 1275 York Avenue, New York, NY 10065.E-mail: donats@mskcc.org
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  • 1

    Jemal A, Siegel R, Ward E et al.. Cancer statistics, 2008. CA Cancer J Clin 2008:58:7196.

  • 2

    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;19:666675.

    • Search Google Scholar
    • Export Citation
  • 3

    Dalbagni G, Genega E, Hashibe M et al.. Cystectomy for bladder cancer: a contemporary series. J Urol 2001;165:11111116.

  • 4

    Bassi P, Ferrante GD, Piazza N et al.. Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort. J Urol 1999;161:14941497.

    • Search Google Scholar
    • Export Citation
  • 5

    Ghoneim MA, el-Mekresh MM, el-Baz MA et al.. Radical cystectomy for carcinoma of the bladder: critical evaluation of the results in 1,026 cases. J Urol 1997;158:393399.

    • Search Google Scholar
    • Export Citation
  • 6

    Knap MM, Lundbeck F, Overgaard J. Prognostic factors, pattern of recurrence and survival in danish bladder cancer cohort treated with radical cystectomy. Acta Oncologica 2003;42:160168.

    • Search Google Scholar
    • Export Citation
  • 7

    Herr HW, Dotan Z, Donat SM, Bajorin DF. Defining optimal therapy for muscle invasive bladder cancer. J Urol 2007;177:437443.

  • 8

    Sternberg CN, Yagoda A, Scher HI et al.. Preliminary results of M-VAC for transitional cell carcinoma of the urothelium. J Urol 1985;133:403404.

  • 9

    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;23:46024608.

    • Search Google Scholar
    • Export Citation
  • 10

    Schultz PK, Herr HW, Zhang ZF et al.. Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up. J Clin Oncol 1994;12:13941401.

    • Search Google Scholar
    • Export Citation
  • 11

    Sonpavde G, Petrylak DP. Perioperative chemotherapy for bladder cancer. Crit Rev Oncol Hematol 2006;57:133144.

  • 12

    Izawa JI, Chin JL, Winquist E. Timing cystectomy and perioperative chemotherapy in the treatment of muscle invasive bladder cancer. Can J Urol 2006;13:4853.

    • Search Google Scholar
    • Export Citation
  • 13

    Dreicer R. Chemotherapy for muscle-invasive bladder cancer in the perioperative setting: current standards. Urol Oncol 2007;25:7275.

    • Search Google Scholar
    • Export Citation
  • 14

    Pectasides D, Pectasides M, Nikolaou M. Adjuvant and neoadjuvant chemotherapy in muscle invasive bladder cancer: literature review. Euro Urol 2005;48:6068.

    • Search Google Scholar
    • Export Citation
  • 15

    Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003;7:19271934.

    • Search Google Scholar
    • Export Citation
  • 16

    Winquist E, Kirchner TS, Segal R et al.. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 2004;171:561569.

    • Search Google Scholar
    • Export Citation
  • 17

    Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48:202206.

    • Search Google Scholar
    • Export Citation
  • 18

    Advanced Bladder Cancer Meta-analysis Collaboration. Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data. Eur Urol 2005;48:189201.

    • Search Google Scholar
    • Export Citation
  • 19

    David KA, Milowsky MI, Ritchey J et al.. Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the national cancer data base. J Urol 2007;178:451454.

    • Search Google Scholar
    • Export Citation
  • 20

    Lehmann N, Retz M, Stockle M. Chemotherapy in the post-MVAC era: the case for adjuvant chemotherapy. World J Urol 2002;20:144150.

  • 21

    Leissner J, Hohenfellner R, Thuroff JW et al.. Lymphadenectomy in patients with transitional cell carcinoma of the bladder: significance for staging and prognosis. BJU Int 2000;85:817821.

    • Search Google Scholar
    • Export Citation
  • 22

    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;167:12951298.

    • Search Google Scholar
    • Export Citation
  • 23

    Konety BR, Joslyn SA, O’Donnell MA. Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the surveillance, epidemiology and end results program data base. J Urol 2003;169:946950.

    • Search Google Scholar
    • Export Citation
  • 24

    Grossman HB, Natale RB, Tangen CM et al.. Neoadjuvant chemotherapy plus cytstectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349:859866.

    • Search Google Scholar
    • Export Citation
  • 25

    Herr HW, Faulkner JR, Grossman HB et al.. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol 2004;22:27812789.

    • Search Google Scholar
    • Export Citation
  • 26

    Raghavan D, Quinn D, Skinner DG, Stein JP. Surgery and adjunctive chemotherapy for invasive bladder cancer. Surg Oncol 2002;11:5563.

  • 27

    Nielsen ME, Palapattu GS, Karakiewicz PI et al.. A delay in radical cystectomy of > 3 months is not associated with a worse clinical outcome. BJU Int 2008;100:10151020.

    • Search Google Scholar
    • Export Citation
  • 28

    Millikan R, Dinney C, Swanson D et al.. Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy wtih both preoperative and postoperative M-VAC. J Clin Oncol 2001;19:40054013.

    • Search Google Scholar
    • Export Citation
  • 29

    Donat SM, Shabsigh A, Savage C et al.. Potential impact of postoperative complications on the timing of adjuvant chemotherapy in patients undergoing radical cystectomy: a high volume tertiary cancer center experience. Eur Urol 2008, in press.

    • Search Google Scholar
    • Export Citation
  • 30

    Rosenberg JE. Current status of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Expert Rev Anticancer Ther 2007;7:17291736.

    • Search Google Scholar
    • Export Citation
  • 31

    Schrag D, Mitra N, Xu F et al.. Cystectomy for muscle invasive bladder cancer: patterns and outcomes of care in the Medicare population. Urology 2005;65:11181125.

    • Search Google Scholar
    • Export Citation
  • 32

    Wallace DM, Raghavan D, Kelly KA et al.. Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder. Br J Urol 1991;67:608615.

    • Search Google Scholar
    • Export Citation
  • 33

    Martinez-Piñeiro JA, Gonzalez Martin M, Arocena F et al.. Neoadjuvant cisplatin chemotherapy before radical cystectomy in invasive transitional cell carcinoma of the bladder: a prospective randomized phase III study. J Urol 1995;153:964973.

    • Search Google Scholar
    • Export Citation
  • 34

    Bassi PF, Pappagallo GL, Sperandio P et al.. Neoadjuvant MVAC chemotherapy of invasive bladder cancer: results of a multicenter phase III trial. J Urol 1999;161:264.

    • Search Google Scholar
    • Export Citation
  • 35

    Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet 1999;354:533540. Erratum in: Lancet 1999;354:1650.

    • Search Google Scholar
    • Export Citation
  • 36

    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;45:297303.

    • Search Google Scholar
    • Export Citation
  • 37

    Sengeløv L, von der Maase H, Lundbeck F et al.. Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours. Acta Oncol 2002;41:447456.

    • Search Google Scholar
    • Export Citation
  • 38

    Studer UE, Bacchi M, Biedermann C et al.. Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial. J Urol 1994;152:8184.

    • Search Google Scholar
    • Export Citation
  • 39

    Skinner DG, Daniels JR, Russell CA et al.. Adjuvant chemotherapy following cystectomy benefits patients with deeply invasive bladder cancer. Semin Urol 1990;8:279284.

    • Search Google Scholar
    • Export Citation
  • 40

    Bono AV, Benvenuti C, Gibba A et al.. Adjuvant chemotherapy in locally advanced bladder cancer. Final analysis of a controlled multicentre study. Acta Urol Ital 1197;11:55.

    • Search Google Scholar
    • Export Citation
  • 41

    Freiha F, Reese J, Torti FM. A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. J Urol 1996;155:495499.

    • Search Google Scholar
    • Export Citation
  • 42

    Stöckle M, Meyenburg W, Wellek S et al.. Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience. J Urol 1995;153:4752.

    • Search Google Scholar
    • Export Citation
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