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Answer 3
  1. Neoadjuvant chemotherapy with MVAC, followed by radical cystoprostatectomy and lymphadenectomy. Two intergroup trials and a meta-analysis have shifted the treatment for muscle-invasive bladder TCC towards the use of neoadjuvant chemotherapy, with between 13% and 24% reduction in mortality.8-10 Compared with local treatment alone, neoadjuvant cisplatin-based chemotherapy was associated with a 14% relative decrease in the risk of death and a 5% absolute survival benefit at 5 years. Many oncologists substitute standard-dose MVAC for 12 weeks (3 cycles) in muscle-invasive TCC of the urothelium with either GC for 12 weeks or high-dose MVAC with granulocyte-colony stimulating factor for 4 cycles (8 weeks). This recommendation is based on the results of 2 randomized controlled studies performed in patients with metastatic disease, which showed that GC and high-dose MVAC are equally effective but less toxic than standard-dose MVAC.11,12

    8. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International Collaboration of Trialists [published erratum appears in Lancet 1999;354:1650]. Lancet 1999;354:533-40.

    9. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer [published erratum appears in N Engl J Med 2003;349:1880]. N Engl J Med 2003;349:859-66.

    10. Advanced Bladder Cancer Overview Collaboration. Neoadjuvant chemotherapy for invasive bladder cancer. Cochrane Database Syst Rev 2005;(2):CD005246.

    11. 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;18:3068-77.

    12. Sternberg CN, de Mulder P, Schornagel JH, et al; EORTC Genito-Urinary Cancer Group. 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 tumors. Eur J Cancer 2006;42:50-4.

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