Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer
- Derek Raghavan, MD, PhD, FACP, FASCO
Derek Raghavan, MD, PhD, FACP, FASCO
- Section Editor — Bladder Cancer
- President, Levine Cancer Institute
- Carolinas HealthCare System
- Charlotte, NC
- Section Editors
- Philip W Kantoff, MD
Philip W Kantoff, MD
- Section Editor — Testicular Cancer
- Chairman of Medicine
- Memorial Sloan Kettering Cancer Center
- Seth P Lerner, MD
Seth P Lerner, MD
- Section Editor — Bladder Cancer
- Beth and Dave Swalm Chair in Urologic Oncology
- Professor of Urology
- Baylor College of Medicine
Worldwide, bladder cancer accounts for approximately 450,000 new cases and 165,000 deaths . In developed areas of the world, such as North America and Western Europe, these bladder cancers are predominantly urothelial.
Despite radical cystectomy, approximately one-half of patients with muscle-invasive urothelial (transitional cell) bladder cancer involving the muscularis propria (T2), perivesical tissue (T3), or pelvic structures (T4) develop metastatic disease within two years (table 1); most of these patients will succumb to their disease [2,3]. (See "Epidemiology and risk factors of urothelial (transitional cell) carcinoma of the bladder", section on 'Epidemiology'.)
The preferred management of patients with muscle-invasive bladder cancer consists of a multimodal approach comprising neoadjuvant chemotherapy followed by radical cystectomy. Despite the evidence that neoadjuvant cisplatin-based chemotherapy improves survival compared with locoregional treatment alone, less than 20 percent of patients undergoing radical cystectomy actually receive neoadjuvant chemotherapy [4-6], although this may be increasing at higher-volume centers .
In appropriately selected patients who are not candidates for radical cystectomy or who prefer to retain their native bladder, a combined-modality approach of maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy is an alternative.
This topic discusses neoadjuvant chemotherapy followed by radical cystectomy for muscle-invasive urothelial bladder cancer. Related topics include:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Sauter G. Bladder Cancer. In: World Cancer Report 2014, Stewart BW, Wild CP (Eds), International Agency for Research on Cancer, Lyon 2014. p.445.
- Raghavan D, Shipley WU, Garnick MB, et al. Biology and management of bladder cancer. N Engl J Med 1990; 322:1129.
- Stenzl A, Cowan NC, De Santis M, et al. The updated EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 2009; 55:815.
- Porter MP, Kerrigan MC, Donato BM, Ramsey SD. Patterns of use of systemic chemotherapy for Medicare beneficiaries with urothelial bladder cancer. Urol Oncol 2011; 29:252.
- Miles BJ, Fairey AS, Eliasziw M, et al. Referral and treatment rates of neoadjuvant chemotherapy in muscle-invasive bladder cancer before and after publication of a clinical practice guideline. Can Urol Assoc J 2010; 4:263.
- Raj GV, Karavadia S, Schlomer B, et al. Contemporary use of perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer. Cancer 2011; 117:276.
- Apolo AB, Kim JW, Bochner BH, et al. Examining the management of muscle-invasive bladder cancer by medical oncologists in the United States. Urol Oncol 2014; 32:637.
- Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003; 361:1927.
- Meeks JJ, Bellmunt J, Bochner BH, et al. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2012; 62:523.
- Zargar H, Espiritu PN, Fairey AS, et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2015; 67:241.
- Galsky MD, Pal SK, Chowdhury S, et al. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer 2015; 121:2586.
- 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; 349:859.
- 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.
- Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet 1999; 354:533.
- Sternberg CN, de Mulder PH, Schornagel JH, et al. 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; 19:2638.
- 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; 42:50.
- Choueiri TK, Jacobus S, Bellmunt J, et al. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol 2014; 32:1889.
- Plimack ER, Hoffman-Censits JH, Viterbo R, et al. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol 2014; 32:1895.
- International Collaboration of Trialists, Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011; 29:2171.
- Mertens LS, Meijer RP, Kerst JM, et al. Carboplatin based induction chemotherapy for nonorgan confined bladder cancer--a reasonable alternative for cisplatin unfit patients? J Urol 2012; 188:1108.
- Russell PJ, Raghavan D, Gregory P, et al. Bladder cancer xenografts: a model of tumor cell heterogeneity. Cancer Res 1986; 46:2035.
- Raghavan D. Progress in the chemotherapy of metastatic cancer of the urinary tract. Cancer 2003; 97:2050.
- Trump DL, Elson P, Madajewicz S, et al. Randomized phase II evaluation of carboplatin and CHIP in advanced transitional cell carcinoma of the urothelium. The Eastern Cooperative Oncology Group. J Urol 1990; 144:1119.
- Raabe NK, Fossa SD, Parø G. Phase II study of carboplatin in locally advanced and metastatic transitional cell carcinoma of the urinary bladder. Br J Urol 1989; 64:604.
- Hansen PV, Glavind K, Panduro J, Pedersen M. Paternity in patients with testicular germ cell cancer: pretreatment and post-treatment findings. Eur J Cancer 1991; 27:1385.
- Hussain M, Vaishampayan U, Du W, et al. Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer. J Clin Oncol 2001; 19:2527.
- Ording AG, Nielsen ME, Smith AB, et al. Venous thromboembolism and effect of comorbidity in bladder cancer: A danish nationwide cohort study of 13,809 patients diagnosed between 1995 and 2011. Urol Oncol 2016; 34:292.e1.
- Duivenvoorden WC, Daneshmand S, Canter D, et al. Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy. J Urol 2016; 196:1627.
- Whitmore WF Jr, Batata MA, Ghoneim MA, et al. Radical cystectomy with or without prior irradiation in the treatment of bladder cancer. J Urol 1977; 118:184.
- Shipley WU, Cummings KB, Coombs LJ, et al. 4,000 RAD preoperative irradiation followed by prompt radical cystectomy for invasive bladder carcinoma: a prospective study of patient tolerance and pathologic downstaging. J Urol 1982; 127:48.
- Cole CJ, Pollack A, Zagars GK, et al. Local control of muscle-invasive bladder cancer: preoperative radiotherapy and cystectomy versus cystectomy alone. Int J Radiat Oncol Biol Phys 1995; 32:331.
- Bloom HJ, Hendry WF, Wallace DM, Skeet RG. Treatment of T3 bladder cancer: controlled trial of pre-operative radiotherapy and radical cystectomy versus radical radiotherapy. Br J Urol 1982; 54:136.
- 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 with both preoperative and postoperative M-VAC. J Clin Oncol 2001; 19:4005.
- deVere White RW, Lara PN Jr, Goldman B, et al. A sequential treatment approach to myoinvasive urothelial cancer: a phase II Southwest Oncology Group trial (S0219). J Urol 2009; 181:2476.
- Sternberg CN, Pansadoro V, Calabrò F, et al. Can patient selection for bladder preservation be based on response to chemotherapy? Cancer 2003; 97:1644.
- 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; 19:666.
- Esrig D, Elmajian D, Groshen S, et al. Accumulation of nuclear p53 and tumor progression in bladder cancer. N Engl J Med 1994; 331:1259.
- Sarkis AS, Bajorin DF, Reuter VE, et al. Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC. J Clin Oncol 1995; 13:1384.
- Garcia del Muro X, Munoz J, Condom E, et al. p21 and p53 as prognostic factors for bladder preservation and survival in patients with bladder cancer treated with neoadjuvant chemotherapy (abstract). Proc Am Soc Clin Oncol 2002; 21:179a.
- Herr HW, Bajorin DF, Scher HI, et al. Can p53 help select patients with invasive bladder cancer for bladder preservation? J Urol 1999; 161:20.
- Kuczyk MA, Bokemeyer C, Serth J, et al. p53 overexpression as a prognostic factor for advanced stage bladder cancer. Eur J Cancer 1995; 31A:2243.
- Tsuji M, Kojima K, Murakami Y, et al. Prognostic value of Ki-67 antigen and p53 protein in urinary bladder cancer: immunohistochemical analysis of radical cystectomy specimens. Br J Urol 1997; 79:367.
- Stadler WM, Lerner SP, Groshen S, et al. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol 2011; 29:3443.
- Takata R, Katagiri T, Kanehira M, et al. Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling. Clin Cancer Res 2005; 11:2625.
- Smith SC, Baras AS, Dancik G, et al. A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol 2011; 12:137.
- Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515:558.
- OVERVIEW OF TREATMENT APPROACH
- NEOADJUVANT CHEMOTHERAPY
- Choice of chemotherapy regimens
- - Classic MVAC
- - Dose-dense MVAC
- Patients with renal insufficiency
- Thromboembolic complications
- NEOADJUVANT RADIATION THERAPY?
- ADJUVANT CHEMOTHERAPY
- RADICAL CYSTECTOMY
- POSTTREATMENT SURVEILLANCE AND TREATMENT
- FUTURE DIRECTIONS
- p53 status for risk-directed clinical trials
- Gene expression profiling
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS