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Journal of Clinical Oncology, Vol 19, Issue 16 (August), 2001: 3622-3634
© 2001 American Society for Clinical Oncology

Prognostic Factors Analysis of 17,600 Melanoma Patients: Validation of the American Joint Committee on Cancer Melanoma Staging System

By Charles M. Balch, Seng-Jaw Soong, Jeffrey E. Gershenwald, John F. Thompson, Douglas S. Reintgen, Natale Cascinelli, Marshall Urist, Kelly M. McMasters, Merrick I. Ross, John M. Kirkwood, Michael B. Atkins, John A. Thompson, Daniel G. Coit, David Byrd, Renee Desmond, Yuting Zhang, Ping-Yu Liu, Gary H. Lyman, Aberto Morabito

From the Johns Hopkins Medical Institutions, Baltimore, MD; American Society of Clinical Oncology, Alexandria, VA; University of Alabama at Birmingham, Birmingham, AL; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Sydney Melanoma Unit, University of Sydney, Sydney, New South Wales, Australia; H. Lee Moffit Cancer Center, University of South Florida, Tampa, FL; Istituto Nazionale Tumori, World Health Organization Melanoma Program, Milan, Italy; University of Louisville Medical Center, Louisville, KY; University of Pittsburgh Medical Center, Pittsburgh, PA; Beth Israel Deaconess Medical Center, Boston, MA; University of Washington Medical Center and Fred Hutchinson Cancer Research Center, Seattle, WA; and Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Charles M. Balch, MD, American Society of Clinical Oncology, 1900 Duke St, Ste 200, Alexandria, VA 22314; email: balchc{at}asco.org

PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal.

PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients.

RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (<= 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients.

CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.


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J. M. Thomas, R. P. A'Hern, J. M. Grichnik, S. Retsas, D. Lipsker, M. H. Kanzler, L. Levitt, A. Lin, D. L. Morton, A. J. Cochran, et al.
Sentinel-Node Biopsy in Melanoma
N. Engl. J. Med., January 25, 2007; 356(4): 418 - 421.
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Y. Miao, K. Benwell, and T. P. Quinn
99mTc- and 111In-Labeled {alpha}-Melanocyte-Stimulating Hormone Peptides as Imaging Probes for Primary and Pulmonary Metastatic Melanoma Detection
J. Nucl. Med., January 1, 2007; 48(1): 73 - 80.
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S. M. Swetter, S. Soon, C. R. Harrington, and S. C. Chen
Effect of Health Care Delivery Models on Melanoma Thickness and Stage in a University-Based Referral Center: An Observational Pilot Study
Arch Dermatol, January 1, 2007; 143(1): 30 - 36.
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J. K. Robinson, R. Turrisi, and J. Stapleton
Efficacy of a Partner Assistance Intervention Designed to Increase Skin Self-examination Performance
Arch Dermatol, January 1, 2007; 143(1): 37 - 41.
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F. Tas, S. Kurul, H. Camlica, and E. Topuz
Malignant Melanoma in Turkey: A Single Institution's Experience on 475 Cases
Jpn. J. Clin. Oncol., December 1, 2006; 36(12): 794 - 799.
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W. Liu, J. P. Dowling, W. K. Murray, G. A. McArthur, J. F. Thompson, R. Wolfe, and J. W. Kelly
Rate of Growth in Melanomas: Characteristics and Associations of Rapidly Growing Melanomas
Arch Dermatol, December 1, 2006; 142(12): 1551 - 1558.
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H Gogas, A Polyzos, I Stavrinidis, K Frangia, D Tsoutsos, P Panagiotou, C Markopoulos, O Papadopoulos, D Pectasides, M Mantzourani, et al.
Temozolomide in combination with celecoxib in patients with advanced melanoma. A phase II study of the Hellenic Cooperative Oncology Group
Ann. Onc., December 1, 2006; 17(12): 1835 - 1841.
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J. Rangel, S. Torabian, L. Shaikh, M. Nosrati, F. L. Baehner, C. Haqq, S. P.L. Leong, J. R. Miller III, R. W. Sagebiel, and M. Kashani-Sabet
Prognostic Significance of Nuclear Receptor Coactivator-3 Overexpression in Primary Cutaneous Melanoma
J. Clin. Oncol., October 1, 2006; 24(28): 4565 - 4569.
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A. van Akkooi, J. de Wilt, C Verhoef, P. Schmitz, A. van Geel, A. Eggermont, and M Kliffen
Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative?
Ann. Onc., October 1, 2006; 17(10): 1578 - 1585.
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D. L. Morton, J. F. Thompson, A. J. Cochran, N. Mozzillo, R. Elashoff, R. Essner, O. E. Nieweg, D. F. Roses, H. J. Hoekstra, C. P. Karakousis, et al.
Sentinel-node biopsy or nodal observation in melanoma.
N. Engl. J. Med., September 28, 2006; 355(13): 1307 - 1317.
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C. M. Balch and N. Cascinelli
Sentinel-Node Biopsy in Melanoma
N. Engl. J. Med., September 28, 2006; 355(13): 1370 - 1371.
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N. Cascinelli, E. Bombardieri, R. Bufalino, T. Camerini, A. Carbone, C. Clemente, L. Lenisa, L. Mascheroni, A. Maurichi, E. Pennacchioli, et al.
Sentinel and Nonsentinel Node Status in Stage IB and II Melanoma Patients: Two-Step Prognostic Indicators of Survival
J. Clin. Oncol., September 20, 2006; 24(27): 4464 - 4471.
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 Arch SurgHome page
R. Essner, R. Scheri, M. Kavanagh, H. Torisu-Itakura, L. A. Wanek, and D. L. Morton
Surgical Management of the Groin Lymph Nodes in Melanoma in the Era of Sentinel Lymph Node Dissection
Arch Surg, September 1, 2006; 141(9): 877 - 884.
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H. Kittler, P. Guitera, E. Riedl, M. Avramidis, L. Teban, M. Fiebiger, R. A. Weger, M. Dawid, and S. Menzies
Identification of clinically featureless incipient melanoma using sequential dermoscopy imaging.
Arch Dermatol, September 1, 2006; 142(9): 1113 - 1119.
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 Genes Dev.Home page
L. Chin, L. A. Garraway, and D. E. Fisher
Malignant melanoma: genetics and therapeutics in the genomic era.
Genes & Dev., August 15, 2006; 20(16): 2149 - 2182.
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J. A. Campillo, J. A. Martinez-Escribano, M. R. Moya-Quiles, L. A. Marin, M. Muro, N. Guerra, A. Parrado, M. Campos, J. F. Frias, A. Minguela, et al.
Natural Killer Receptors on CD8 T Cells and Natural Killer Cells from Different HLA-C Phenotypes in Melanoma Patients.
Clin. Cancer Res., August 15, 2006; 12(16): 4822 - 4831.
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S. Mocellin, D. Hoon, A. Ambrosi, D. Nitti, and C. R. Rossi
The Prognostic Value of Circulating Tumor Cells in Patients with Melanoma: A Systematic Review and Meta-analysis
Clin. Cancer Res., August 1, 2006; 12(15): 4605 - 4613.
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A. J. Miller and M. C. Mihm Jr.
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N. Engl. J. Med., July 6, 2006; 355(1): 51 - 65.
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S. J. Moschos, H. D. Edington, S. R. Land, U. N. Rao, D. Jukic, J. Shipe-Spotloe, and J. M. Kirkwood
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
J. Clin. Oncol., July 1, 2006; 24(19): 3164 - 3171.
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C. R. Scoggins, M. I. Ross, D. S. Reintgen, R. D. Noyes, J. S. Goydos, P. D. Beitsch, M. M. Urist, S. Ariyan, B. S. Davidson, J. J. Sussman, et al.
Prospective Multi-Institutional Study of Reverse Transcriptase Polymerase Chain Reaction for Molecular Staging of Melanoma
J. Clin. Oncol., June 20, 2006; 24(18): 2849 - 2857.
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T. A. Aloia, J. E. Gershenwald, R. H. Andtbacka, M. M. Johnson, C. W. Schacherer, C. S. Ng, J. N. Cormier, J. E. Lee, M. I. Ross, and P. F. Mansfield
Utility of Computed Tomography and Magnetic Resonance Imaging Staging Before Completion Lymphadenectomy in Patients With Sentinel Lymph Node-Positive Melanoma
J. Clin. Oncol., June 20, 2006; 24(18): 2858 - 2865.
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 JNMHome page
T. Z. Belhocine, A. M. Scott, E. Even-Sapir, J.-L. Urbain, and R. Essner
Role of Nuclear Medicine in the Management of Cutaneous Malignant Melanoma
J. Nucl. Med., June 1, 2006; 47(6): 957 - 967.
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P. S. Reddy, S. Ganesh, and D.-C. Yu
Enhanced gene transfer and oncolysis of head and neck cancer and melanoma cells by fiber chimeric oncolytic adenoviruses.
Clin. Cancer Res., May 1, 2006; 12(9): 2869 - 2878.
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T. Kakinuma and S. T. Hwang
Chemokines, chemokine receptors, and cancer metastasis
J. Leukoc. Biol., April 1, 2006; 79(4): 639 - 651.
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 Ann OncolHome page
D. Schadendorf, S. Ugurel, B. Schuler-Thurner, F. O. Nestle, A. Enk, E.-B. Brocker, S. Grabbe, W. Rittgen, L. Edler, A. Sucker, et al.
Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG
Ann. Onc., April 1, 2006; 17(4): 563 - 570.
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M. I. Ross
Early-stage melanoma: staging criteria and prognostic modeling.
Clin. Cancer Res., April 1, 2006; 12(7): 2312s - 2319s.
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 Mayo Clin Proc.Home page
D. L. Cummins, J. M. Cummins, H. Pantle, M. A. Silverman, A. L. Leonard, and A. Chanmugam
Cutaneous Malignant Melanoma
Mayo Clin. Proc., April 1, 2006; 81(4): 500 - 507.
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 JCOHome page
H. M. Shaw, M. J. Quinn, R. A. Scolyer, and J. F. Thompson
Survival in Patients With Desmoplastic Melanoma
J. Clin. Oncol., March 10, 2006; 24(8): e12 - e12.
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D. P. Livestro, A. Sober, and K. K. Tanabe
In Reply:
J. Clin. Oncol., March 10, 2006; 24(8): e13 - e13.
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M. J. Reinhardt, A. Y. Joe, U. Jaeger, A. Huber, A. Matthies, J. Bucerius, R. Roedel, H. Strunk, T. Bieber, H.-J. Biersack, et al.
Diagnostic Performance of Whole Body Dual Modality 18F-FDG PET/CT Imaging for N- and M-Staging of Malignant Melanoma: Experience With 250 Consecutive Patients
J. Clin. Oncol., March 1, 2006; 24(7): 1178 - 1187.
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R. Dummer, C. Garbe, J. A. Thompson, A. M. Eggermont, K. Yoo, T. Maier, and B. Bergstrom
Randomized Dose-Escalation Study Evaluating Peginterferon Alfa-2a in Patients With Metastatic Malignant Melanoma
J. Clin. Oncol., March 1, 2006; 24(7): 1188 - 1194.
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 NEJMHome page
H. Gogas, J. Ioannovich, U. Dafni, C. Stavropoulou-Giokas, K. Frangia, D. Tsoutsos, P. Panagiotou, A. Polyzos, O. Papadopoulos, A. Stratigos, et al.
Prognostic Significance of Autoimmunity during Treatment of Melanoma with Interferon
N. Engl. J. Med., February 16, 2006; 354(7): 709 - 718.
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H. Schmidt, J. S. Johansen, P. Sjoegren, I. J. Christensen, B. S. Sorensen, K. Fode, J. Larsen, and H. von der Maase
Serum YKL-40 Predicts Relapse-Free and Overall Survival in Patients With American Joint Committee on Cancer Stage I and II Melanoma
J. Clin. Oncol., February 10, 2006; 24(5): 798 - 804.
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R. F. Uren
Sentinel Lymph Node Biopsy in Melanoma
J. Nucl. Med., February 1, 2006; 47(2): 191 - 195.
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D. Berd, M. J. Mastrangelo, and T. Sato
Calculation of Survival of Patients With Stage III Melanoma
J. Clin. Oncol., December 20, 2005; 23(36): 9427 - 9427.
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C. M. Balch, S.-J. Soong, and R. Desmond
In Reply:
J. Clin. Oncol., December 20, 2005; 23(36): 9428 - 9428.
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R. W. Weber, S. O'Day, M. Rose, R. Deck, P. Ames, J. Good, J. Meyer, R. Allen, S. Trautvetter, M. Timmerman, et al.
Low-Dose Outpatient Chemobiotherapy With Temozolomide, Granulocyte-Macrophage Colony Stimulating Factor, Interferon-{alpha}2b, and Recombinant Interleukin-2 for the Treatment of Metastatic Melanoma
J. Clin. Oncol., December 10, 2005; 23(35): 8992 - 9000.
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J. M. Kirkwood
Building Upon the Standard of Care in Adjuvant Therapy of High-Risk Melanoma
J. Clin. Oncol., December 1, 2005; 23(34): 8559 - 8563.
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