FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 349:859-866 August 28, 2003 Number 9 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article PubMed Citation

ABSTRACT

Background Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy.

Methods Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy.

Results We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001).

Conclusions As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.

Source Information

From the M.D. Anderson Cancer Center, Houston (H.B.G.); Cedars–Sinai Comprehensive Cancer Center, Los Angeles (R.B.N.); the Southwest Oncology Group Statistical Center, Seattle (C.M.T.); Scott and White Clinic, Temple, Tex. (V.O.S.); the University of Chicago Cancer Research Center, Chicago (N.J.V.); the University of Pittsburgh School of Medicine, Pittsburgh (D.L.T.); the University of California, Davis, Sacramento (R.W.D.W.); the University of Texas Health Science Center, San Antonio, San Antonio (M.F.S.); Wayne State University Medical Center, Detroit (D.P.W.); the University of Southern California School of Medicine, Los Angeles (D.R.); and the University of Colorado, Denver (E.D.C.).

Address reprint requests to the Southwest Oncology Group (SWOG-8710) Operations Office at 14980 Omicron Dr., San Antonio, TX 78245-3217.

Full Text of this Article

Related Letters:

Chemotherapy for Bladder Cancer
Muñoz A., Barceló J. R., López-Vivanco G., Sonpavde G., Rawat A., Naveed F., Grossman H. B., Tangen C. M.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:2272-2273, Dec 4, 2003. Correspondence

This article has been cited by other articles:

• Pollard, C., Nitz, M., Baras, A., Williams, P., Moskaluk, C., Theodorescu, D. (2009). Genoproteomic Mining of Urothelial Cancer Suggests {gamma}-Glutamyl Hydrolase and Diazepam-Binding Inhibitor as Putative Urinary Markers of Outcome after Chemotherapy. Am. J. Pathol. 175: 1824-1830 [Abstract] [Full Text]  
• Kibel, A. S., Dehdashti, F., Katz, M. D., Klim, A. P., Grubb, R. L., Humphrey, P. A., Siegel, C., Cao, D., Gao, F., Siegel, B. A. (2009). Prospective Study of [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Staging of Muscle-Invasive Bladder Carcinoma. JCO 27: 4314-4320 [Abstract] [Full Text]  
• Efstathiou, J. A., Bae, K., Shipley, W. U., Kaufman, D. S., Hagan, M. P., Heney, N. M., Sandler, H. M. (2009). Late Pelvic Toxicity After Bladder-Sparing Therapy in Patients With Invasive Bladder Cancer: RTOG 89-03, 95-06, 97-06, 99-06. JCO 27: 4055-4061 [Abstract] [Full Text]  
• Gallagher, D. J., Kemeny, N. E. (2009). Colorectal Hepatic Metastases: Adjuvant Chemotherapy and Survival. JCO 27: e18-e19 [Full Text]  
• Sonpavde, G., Elfiky, A. A., Rosenberg, J. E. (2009). Review: Novel agents for advanced bladder cancer. Therapeutic Advances in Medical Oncology 1: 37-50 [Abstract]  
• Messing, E. M., Madeb, R., Feng, C., Stephenson, L., Gilchrist, K. W., Young, T., Gee, J. (2009). Grade and Stage at Presentation Do Not Predict Mortality in Patients With Bladder Cancer Who Survive Their Disease. JCO 27: 2443-2449 [Abstract] [Full Text]  
• Bellmunt, J., Albiol, S., Kataja, V., On behalf of the ESMO Guidelines Working Group, (2009). Invasive bladder cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol 20: iv79-iv80 [Full Text]  
• Rosenberg, J. E., Hahn, W. C. (2009). Bladder cancer: modeling and translation. Genes Dev. 23: 655-659 [Abstract] [Full Text]  
• Boorjian, S. A., Sheinin, Y., Crispen, P. L., Farmer, S. A., Lohse, C. M., Kuntz, S. M., Leibovich, B. C., Kwon, E. D., Frank, I. (2008). T-Cell Coregulatory Molecule Expression in Urothelial Cell Carcinoma: Clinicopathologic Correlations and Association with Survival. Clin. Cancer Res. 14: 4800-4808 [Abstract] [Full Text]  
• Sweeney, C., Bajorin, D. F., Sternberg, C. N. (2008). Muscle-invasive Bladder Cancer: What Have We Learned and What's New on the Horizon?. Am Soc Clin Oncol Ed Book 2008: 200-208 [Abstract] [Full Text]  
• Glynne-Jones, R., Hoskin, P. (2007). Neoadjuvant Cisplatin Chemotherapy Before Chemoradiation: A Flawed Paradigm?. JCO 25: 5281-5286 [Abstract] [Full Text]  
• Kanehira, M., Katagiri, T., Shimo, A., Takata, R., Shuin, T., Miki, T., Fujioka, T., Nakamura, Y. (2007). Oncogenic Role of MPHOSPH1, a Cancer-Testis Antigen Specific to Human Bladder Cancer. Cancer Res. 67: 3276-3285 [Abstract] [Full Text]  
• Parekh, D. J., Bochner, B. H., Dalbagni, G. (2006). Superficial and Muscle-Invasive Bladder Cancer: Principles of Management for Outcomes Assessments. JCO 24: 5519-5527 [Abstract] [Full Text]  
• Garcia, J. A., Dreicer, R. (2006). Systemic Chemotherapy for Advanced Bladder Cancer: Update and Controversies. JCO 24: 5545-5551 [Abstract] [Full Text]  
• Shariat, S. F., Karakiewicz, P. I., Palapattu, G. S., Amiel, G. E., Lotan, Y., Rogers, C. G., Vazina, A., Bastian, P. J., Gupta, A., Sagalowsky, A. I., Schoenberg, M., Lerner, S. P. (2006). Nomograms Provide Improved Accuracy for Predicting Survival after Radical Cystectomy.. Clin. Cancer Res. 12: 6663-6676 [Abstract] [Full Text]  
• Maluf, F., Cordon-Cardo, C, Verbel, D., Satagopan, J., Boyle, M., Herr, H, Bajorin, D. (2006). Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment. Ann Oncol 17: 1677-1686 [Abstract] [Full Text]  
• Sawhney, R, Bourgeois, D, Chaudhary, U. (2006). Neo-adjuvant chemotherapy for muscle-invasive bladder cancer: a look ahead. Ann Oncol 17: 1360-1369 [Abstract] [Full Text]  
• Raj, G. V., Iasonos, A., Herr, H., Donat, S. M. (2006). Formulas Calculating Creatinine Clearance Are Inadequate for Determining Eligibility for Cisplatin-Based Chemotherapy in Bladder Cancer. JCO 24: 3095-3100 [Abstract] [Full Text]  
• Moschos, S. J., Edington, H. D., Land, S. R., Rao, U. N., Jukic, D., Shipe-Spotloe, J., Kirkwood, J. M. (2006). Neoadjuvant Treatment of Regional Stage IIIB Melanoma With High-Dose Interferon Alfa-2b Induces Objective Tumor Regression in Association With Modulation of Tumor Infiltrating Host Cellular Immune Responses. JCO 24: 3164-3171 [Abstract] [Full Text]  
• Cohen, S. M., Goel, A., Phillips, J., Ennis, R. D., Grossbard, M. L. (2006). The Role of Perioperative Chemotherapy in the Treatment of Urothelial Cancer. The Oncologist 11: 630-640 [Abstract] [Full Text]  
• Teramukai, S., Nishiyama, H., Matsui, Y., Ogawa, O., Fukushima, M. (2006). Evaluation for Surrogacy of End Points by Using Data from Observational Studies: Tumor Downstaging for Evaluating Neoadjuvant Chemotherapy in Invasive Bladder Cancer. Clin. Cancer Res. 12: 139-143 [Abstract] [Full Text]  
• Galsky, M. D. (2005). The Role of Taxanes in the Management of Bladder Cancer. The Oncologist 10: 792-798 [Abstract] [Full Text]  
• Lotan, Y., Gupta, A., Shariat, S. F., Palapattu, G. S., Vazina, A., Karakiewicz, P. I., Bastian, P. J., Rogers, C. G., Amiel, G., Perotte, P., Schoenberg, M. P., Lerner, S. P., Sagalowsky, A. I. (2005). Lymphovascular Invasion Is Independently Associated With Overall Survival, Cause-Specific Survival, and Local and Distant Recurrence in Patients With Negative Lymph Nodes at Radical Cystectomy. JCO 23: 6533-6539 [Abstract] [Full Text]  
• Galsky, M. D., Scher, H. I. (2005). Bladder Cancer "Adjuvant-Lite": Tastes Great (works as well) and Less Filling (less toxic)?. JCO 23: 4823-4826 [Full Text]  
• Lehmann, J., Retz, M., Wiemers, C., Beck, J., Thuroff, J., Weining, C., Albers, P., Frohneberg, D., Becker, T., Funke, P.-J., Walz, P., Langbein, S., Reiher, F., Schiller, M., Miller, K., Roth, S., Kalble, T., Sternberg, D., Wellek, S., Stockle, M. (2005). Adjuvant Cisplatin Plus Methotrexate Versus Methotrexate, Vinblastine, Epirubicin, and Cisplatin in Locally Advanced Bladder Cancer: Results of a Randomized, Multicenter, Phase III Trial (AUO-AB 05/95). JCO 23: 4963-4974 [Abstract] [Full Text]  
• Takata, R., Katagiri, T., Kanehira, M., Tsunoda, T., Shuin, T., Miki, T., Namiki, M., Kohri, K., Matsushita, Y., Fujioka, T., Nakamura, Y. (2005). Predicting Response to Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Neoadjuvant Chemotherapy for Bladder Cancers through Genome-Wide Gene Expression Profiling. Clin. Cancer Res. 11: 2625-2636 [Abstract] [Full Text]  
• Lange, P. H., Lin, D. W. (2004). Does the Who and How of Surgery in Bladder Cancer Matter?. JCO 22: 2762-2764 [Full Text]  
• Herr, H. W., Faulkner, J. R., Grossman, H. B., Natale, R. B., deVere White, R., Sarosdy, M. F., Crawford, E. D. (2004). Surgical Factors Influence Bladder Cancer Outcomes: A Cooperative Group Report. JCO 22: 2781-2789 [Abstract] [Full Text]  
• Tsukamoto, T., Kitamura, H., Takahashi, A., Masumori, N. (2004). Treatment of Invasive Bladder Cancer: Lessons from the Past and Perspective for the Future. Jpn J Clin Oncol 34: 295-306 [Abstract] [Full Text]  
• Bamias, A., Deliveliotis, Ch., Fountzilas, G., Gika, D., Anagnostopoulos, A., Zorzou, M.P., Kastritis, E., Constantinides, C., Kosmidis, P., Dimopoulos, M.A. (2004). Adjuvant Chemotherapy With Paclitaxel and Carboplatin in Patients With Advanced Carcinoma of the Upper Urinary Tract: A Study by the Hellenic Cooperative Oncology Group. JCO 22: 2150-2154 [Abstract] [Full Text]  
• Bajorin, D. (2004). The Phase III Candidate: Can We Improve the Science of Selection?. JCO 22: 211-213 [Full Text]  
• Takahashi, A., Tsukamoto, T., Tobisu, K.-i., Shinohara, N., Sato, K., Tomita, Y., Komatsubara, S.-i., Nishizawa, O., Igarashi, T., Fujimoto, H., Nakazawa, H., Komatsu, H., Sugimura, Y., Ono, Y., Kuroda, M., Ogawa, O., Hirao, Y., Hayashi, T., Tsushima, T., Kakehi, Y., Arai, Y., Ueda, S.-i., Nakagawa, M. (2004). Radical Cystectomy for Invasive Bladder Cancer: Results of Multi-institutional Pooled Analysis. Jpn J Clin Oncol 34: 14-19 [Abstract] [Full Text]  
• Munoz, A., Barcelo, J. R., Lopez-Vivanco, G., Sonpavde, G., Rawat, A., Naveed, F., Grossman, H. B., Tangen, C. M. (2003). Chemotherapy for Bladder Cancer. NEJM 349: 2272-2273 [Full Text]  
• Unger, J. M., LeBlanc, M., Crowley, J. J., Grossman, H. B., Natale, R. B., Wozniak, A. J., Berenson, J. R., List, A. F., Peters, W. A. III, Flanigan, R. C., Macdonald, J. S., Al-Sarraf, M., Thompson, I. M., Coltman, C. A. Jr (2003). Estimating the Impact of New Clinical Trial Proven Cancer Therapy and Cancer Chemoprevention on Population Mortality: The Karnofsky Memorial Lecture. JCO 21: 246s-252 [Abstract] [Full Text]  
• Spurgeon, D. (2003). Chemotherapy before surgery improves survival from bladder cancer. BMJ 327: 520- [Full Text]