Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases

Zhihong Chi, Siming Li, Xinan Sheng, Lu Si, Chuanliang Cui, Mei Han, Jun Guo, Zhihong Chi, Siming Li, Xinan Sheng, Lu Si, Chuanliang Cui, Mei Han, Jun Guo

Abstract

Background: Malignant melanoma is a rare disease in Asia, and knowledge on its characteristics and clinical outcome in Asian patients is limited. The purpose of this observational study was to determine the clinical presentation and outcome of patients with melanoma in China.

Methods: A database was prospectively established for the purpose of this analysis. The elements of the database included basic demographic data of patients and prognosticators previously reported in literature, as well as follow-up data including clinical outcome after treatment. Medical record of all patients with pathologically diagnosed malignant melanoma consulted in our center since 2006 were retrieved and reviewed. No patient was excluded in this study. Statistical analyses including survival and multivariate analyses of factors associated with survival were respectively performed by Kaplan-Meier method and Cox proportional hazard model.

Results: A total of 522 consecutive and nonselected cases were evaluated. There were 218 cases (41.8%) of acral lentiginous melanoma (ALM), 118 (22.6%) of mucosal melanoma (MCM), 103 (19.7%) of nodular melanoma (NM), 33 (6.3%) of superficial spreading melanoma (SSM), and others were Lentigo maligna melanoma or unclassifiable disease. The proportion of patients with clinical stage I, II, III, and IV diseases were 6.1%, 55.9%, 25.1%, and 12.8%, respectively. Among the 357 cases of cutaneous melanoma, 234 patients (65.5%) had ulceration.The 5-year overall survival rate of all 522 patients was 41.6%, and the median survival time was 3.92 years (95% CI, 3.282 to 4.558). Five-year survival rates of patients with stage I, II, III, and IV diseases were 94.1%, 44.0%, 38.4% and 4.6% respectively (P < 0.001). Multivariate analysis revealed that clinical stage and the ulceration were two significant prognosticators for OS. In addition, extent of surgery and use of adjuvant therapy were significant prognosticators for DFS in patients with non-metastatic disease after definitive treatment. Pathological subtype was not a significant prognostic factor to predict wither OS or DFS.

Conclusions: Prognoses of patients with malignant melanoma diagnosed in China were suboptimal, and most patients were diagnosed with locally advanced disease (i.e., stage II or above). ALM and MCM are the two most commonly diagnosed pathological subtypes. Clinical staging and presence of ulceration was significantly associated with clinical outcome in terms of OS, while treatment strategy including extent of surgery and use of adjuvant therapy were significant predictors of DFS.

Figures

Figure 1
Figure 1
Patient distribution by (A) anatomic location (H-N, head and neck) and (B) histological type (Un, unclassifiable).
Figure 2
Figure 2
Kaplan-Meier analyses of overall survival (OS) for the entire group of patients according to different stratums by prognostic factors (overall comparison was administered by Mantel-Cox log-rank test). Overall survival (A), OS based on stage (P < .001) (B), histology (P < .001) (C), MCM and non-MCM patients (P = .036) (D), Breslow thickness (P = .29) (E), and Ulceration status (P = .08) (F).
Figure 3
Figure 3
Kaplan-Meier analyses of disease-free survival (DFS) of 450 patients with stage I-III melanoma received definitive therapy according to different stratums by prognostic factors (overall comparison was performed by Mantel-Cox log-rank test): (A) Male vs. Female (P = .035), (B) DFS estimates according to stage (P < .001), (C) DFS of patients receiving different excision (EE for extended excision, LE for local excision, LND for lymph node dissection) of primary tumor (P < .001), (D) DFS of patients receiving different adjuvant therapy (P < .001).

References

    1. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P. Cancer Incidence in Five Continents. IX. IARC Scientific Publications No. 160, Lyon: IARC; 2007.
    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–249. doi: 10.3322/caac.20006.
    1. Cormier JN, Xing Y, Ding M, Lee JE, Mansfield PF, Gershenwald JE, Ross MI, Du XL. Ethnic differences among patients with cutaneous melanoma. Arch Internal Medicine. 2006;166:1907–1914. doi: 10.1001/archinte.166.17.1907.
    1. Halder RM, Bridgeman-Shah S. Skin cancer in African Americans. Cancer. 1995;75(2 Suppl):667–673. doi: 10.1002/1097-0142(19950115)75:2+<667::AID-CNCR2820751409>;2-I.
    1. Bellows CF, Belafsky P, Fortgang IS, Beech DJ. Melanoma in African-Americans: trends in biological behavior and clinical characteristics over two decades. J Surg Oncol. 2001;78(1):10–6. doi: 10.1002/jso.1116.
    1. Shoo BA, Kashani-Sabet M. Melanoma arising in African-, Asian-, Latino- and Native-American populations. Semin Cutan Med Surg. 2009;28(2):96–102. doi: 10.1016/j.sder.2009.04.005.
    1. Ishihara K, Saida T, Yamamoto A. Updated statistical data for malignant melanoma in Japan. Int J Clin Oncol. 2001;6(3):109–116. doi: 10.1007/PL00012091.
    1. Ishihara K, Saida T, Otsuka F, Yamazaki N. Statistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update. Int J Clin Oncol. 2008;13(1):33–41. doi: 10.1007/s10147-007-0751-1.
    1. Chang JW, Yeh KY, Wang CH, Yang TS, Chiang HF, Wei FC, Kuo TT, Yang CH. Malignant melanoma in Taiwan: a prognostic study of 181 cases. Melanoma Res. 2004;14(6):537–541. doi: 10.1097/00008390-200412000-00016.
    1. Balch CM, buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19(16):3635–3648.
    1. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481. doi: 10.2307/2281868.
    1. Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK. SEER Cancer Statistics Review, 1975-2007. National Cancer Institute. Bethesda, MD; 2010. Accessed on November 25, 2010.
    1. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996;14(1):7–17.
    1. MacKie RM, Bray C, Vestey J, Doherty V, Evans A, Thomson D, Nicolson M. Melanoma incidence and mortality in Scotland 1979-2003. Br J Cancer. 2007;96(11):1772–1777. doi: 10.1038/sj.bjc.6603801.
    1. Markovic SN, Erickson LA, Rao RD, Weenig RH, Pockaj BA, Bardia A, Vachon CM, Schild SE, McWilliams RR, Hand JL, Laman SD, Kottschade LA, Maples WJ, Pittelkow MR, Pulido JS, Cameron JD, Creagan ET. Malignant Melanoma in the 21st Century, Part 2: Staging, Prognosis, and Treatment. Mayo Clin Proc. 2007;82(4):490–513. doi: 10.4065/82.4.490.
    1. Ishihara K, Saida T, Yamamoto A. Nationwide survey of malignant melanoma (1992-1998) Skin Cancer (Japan) 2000;15(1):7–14.
    1. Gimotty PA, Botbyl J, Soong SH, Guerry D. A population-based validation of the American Joint Committee on Cancer Melanoma Staging System. J Clin Oncol. 2005;23(31):8065–8075. doi: 10.1200/JCO.2005.02.4976.
    1. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, Urist M, McMasters KM, Ross MI, Kirkwood JM, Atkins MB, Thompson JA, Coit DG, Byrd D, Desmond R, Zhang Y, Liu PY, Lyman GH, Morabito A. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622–3634.
    1. Bradford PT, Goldstein AM, McMaster ML, Tucker MA. Acral lentiginous melanoma: Incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009;145(4):427–434. doi: 10.1001/archdermatol.2008.609.
    1. Reed RJ. New Concepts in Surgical Pathology of the Skin. New York: John Wiley & Sons; 1976. pp. 89–90.
    1. Krementz ET, Feed RJ, Coleman WP, Sutherland CM, Carter RD, Campbell M. Acral lentiginous melanoma. A clinicopathologic entity. Ann Surg. 1982;195(5):632–645. doi: 10.1097/00000658-198205000-00013.
    1. Ishihara K, Saida T, Otsuka F, Yamazaki N. Staistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update. Int J Clin Oncol. 2008;13(1):33–41. doi: 10.1007/s10147-007-0751-1.
    1. Mendenhall WM, Amdur RJ, Hinerman RW, Werning JW, Villaret DB, Mendenhall NP. Head and neck mucosal melanoma. Am J Clin Oncol. 2005;28(6):626–630. doi: 10.1097/01.coc.0000170805.14058.d3.
    1. Henderson MA, Burmeister B, Thompson JF, Di lulio J, Fisher R, Hong A, Scolyer R, Shannon K, Hoesktra H, Ainslie J. Adjuvant radiotherapy and regional lymph node field control in melanoma patients after lymphadenectomy: Results of an intergroup randomized trial (ANZMTG 01.02/TROG 02.01) J Clin Oncol. 2009;27(18s) suppl; abstr LBA9084.
    1. Verma S, Quirt I, McCready D, Bak K, Charette M, Iscoe N. Systematic review of systemic adjuvant therapy for patients at high risk for recurrent melanoma. Cancer. 2006;106(7):1431–42. doi: 10.1002/cncr.21760.
    1. Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2010;102(7):493–501. doi: 10.1093/jnci/djq009.
    1. Sasse AD, Sasse EC, Clark LG, Ulloa L, Clark OA. Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma. Cochrane Database Syst Rev. 2007;1:CD005413.
    1. Hainsworth JD, Infante JR, Spigel DR, Peyton JD, Thompson DS, Lane CM, Clark BL, Rubin MS, Trent DF, Burris HA. Bevacizumab and everolimus in the treatment of patients with metastatic melanoma: a phase 2 trial of the Sarah Cannon Oncology Research Consortium. Cancer. 2010;116(17):4122–4129. doi: 10.1002/cncr.25320.
    1. Vihinen PP, Hernberg M, Vuoristo MS, Tyynelä K, Laukka M, Lundin J, Ivaska J, Pyrhönen S. A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-alpha2a as first line treatment in metastatic melanoma. Melanoma Res. 2010;20(4):318–325. doi: 10.1097/CMR.0b013e3283390365.
    1. Hauschild A, Agarwala SS, Trefzer U, Hogg D, Robert C, Hersey P, Eggermont A, Grabbe S, Gonzalez R, Gille J, Peschel C, Schadendorf D, Garbe C, O'Day S, Daud A, White JM, Xia C, Patel K, Kirkwood JM, Keilholz U. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009;27(17):2823–2830. doi: 10.1200/JCO.2007.15.7636.
    1. O'Day S, Hodi FS, McDermott DF, Weber RW, Sosman JA, Haanen JB, Zhu X, Yellin MJ, Hoos A, Urba WJ. A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 peptide vaccine and the combination in patients with previously treated, unresectable stage III or IV melanoma. J Clin Oncol. 2010;28(18s) suppl; abstr 4.

Source: PubMed

3
Sottoscrivi