Opinion statement
Intermediate and high risk for recurrence melanoma comprise a unique subset of patients with surgically treatable melanoma for whom cure is possible but relapse and distant metastases likely. Strategies to improve the prognosis for such patients with effective adjuvant therapies are critical. In recent randomized trials conducted by the cooperative groups in the United States of patients at high risk for recurrence (patients with thick primary melanomas and those with regional lymph node metastases) administered adjuvant therapy with high-dose interferon alfa-2b (HDI), relapse-free survival and overall survival rates improved significantly. Research efforts in this area continue to assess the role of intermediate-dose interferon, but there is no convincing evidence of success of the lower-dose regimens, despite the reduction in toxicity. For a subset of patients at highest risk (two or more involved lymph nodes), a regimen of therapy for metastatic stage IV melanoma (interleukin-2 based biochemotherapy) is being compared with HDI in an ongoing phase III trial. For intermediate-risk melanoma, no effective adjuvant therapy is available. For such patients, enrollment in ongoing clinical trials assessing the role of shorter courses of HDI or vaccines should be encouraged.
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References and Recommended Reading
Balch CM, Buzaid A, Atkins MB, et al.: A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer 2000, 88:1484–1491.
Balch CM, Buzaid AC, Soong S-J, et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma (original reports: melanoma). J Clin Oncol 2001, 19:3635–3648.
Buzaid AC, Ross MI, Balch CM, et al.: Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system. J Clin Oncol 1997, 15:1039–1051.
Kirkwood JM, Strawderman MH, Ernstoff MS, et al.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996, 14:7–17.
Kirkwood JM, Strawderman MH, Ernstoff MS, et al.: Adjuvant therapy of high-risk melanoma: the role of high-dose interferon α-2b. In Adjuvant Therapy of Cancer VIII. Edited by Salmon SE. Philadelphia: Lippincott-Raven; 1997:251–257.
Cole BF, Gelber RD, Kirkwood JM, et al.: A quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment for high-risk resected cutaneous melanoma: an Eastern Cooperative Oncology Group study (E1684). J Clin Oncol 1996, 14:2666–2673.
Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 2000, 18:2444–2458.
Bystryn J-C, Ferrone S, Livingston P, et al.: Immunotherapy of cancer with vaccines. Ann Clin Lab Sci 1993, 690:355–357.
Livingston PO: The case for melanoma vaccines that induce antibodies. In Molecular Diagnosis and Treatment of Melanoma. Edited by Kirkwood JM. New York: Marcel Dekker; 1997:139-157.
Kirkwood JM, Ibrahim J, Sosman JA, et al.: High-dose interferon alfa-2b significantly prolonged relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/ C509801. J Clin Oncol 2001, 19:2370–2380.
Veronesi U, Cascinelli N, Adamus J, et al.: Thin stage I primary cutaneous malignant melanoma: comparison of excision with margins of 1 or 3 cm. N Engl J Med 1988, 318:1159–1162.
Balch CM, Urist MM, Karakousis CP, et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1-4 mm): results of a multi-institutional randomized surgical trial. Ann Surg 1993, 218:262–269.
Balch CM, Soong S, Ross MI, et al.: Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol 2001, 7:87–97.
Santinarni M, Maurici A, Patuzzo R, et al.: Impact of clinical trials on the treatment of melanoma. Surg Oncol Clin North Am 2001, 10:935–947.
Heaton KM, Sussman JJ, Greshenwald JE, et al.: Surgical margins and prognostic factors in patients with thick (>4 mm) primary melanoma. Ann Surg Oncol 1998, 5:322–328.
Morton DL, Wen D-R, Foshag LJ, et al.: Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck. J Clin Oncol 1993, 11:1751–1756.
Reintgen D, Cruse CW, Wells K, et al.: The orderly progression of melanoma nodal metastases. Ann Surg 1994, 220:759–767.
Gershenwald JE, Thompson W, Mansfield PF, et al.: Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph bode status in 612 stage I or II melanoma patients. J Clin Oncol 1999, 17:976–983.
Reintgen D, Shivers S: Sentinel lymph node micrometastasis from melanoma: proven methodology and evolving significance. Cancer 1999, 86:551–552.
Morton DL, Thompson JF, Essner R, et al.: Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma. Ann Surg 1999, 230:453–465.
Gershenwald JE, Colome MI, Lee JE, et al.: Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol 1998, 16:2253–2260.
Veronesi U, Adamus J, Bandiera DC, et al.: Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. Cancer 1982, 49:2420–2430.
Coit DG, Brennan MF: Extent of lymph node dissection in melanoma of the trunk or lower extremity. Arch Surg 1989, 124:162–166.
Cascinelli N, Morabito A, Santinami M, et al.: Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomized trial. Lancet 1998, 351:793–796.
Marchalonis JJ, Schluter SF: Evolution of variable and constant domains and joining segments of rearranging immunoglobulins. FASEB J 1989, 3:2469–2479.
Morton DL, Foshag LJ, Hoon DS, et al.: Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg 1992, 216:463–482.
Berd D, Maguire HC Jr, McCue P, Mastrangelo MJ: Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. J Clin Oncol 1990, 8:1858–1867.
Berd D, Maguire HC Jr, Schuchter LM, et al.: Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment after resection of nodal metastasis. J Clin Oncol 1997, 15:2359–2370.
Wallack MK, Sivanandham M, Balch CM, et al.: A phase III randomized, double-blind, multiinstitutional trial of vaccinia melanoma oncolysate-active specific immunotherapy for patients with stage II melanoma. Cancer 1995, 75:34–42.
Hersey P, Coates A, McCarthy WH, et al.: A randomized controlled trial of vaccinia melanoma cell lysates (VMCL) in immunotherapy of stage IIb and III melanoma. Melanoma Res 2001, 11:S39-S40.
Sosman JA, Unger JM, Liu P, et al.: Significant impact of HLA class I alleles on outcome in T3NO melanoma patients with melacine (MEL): an allogenic melanoma cell lysate vaccine: prospective analysis of Southwest Oncology Group (SWOG)-9035. Proc ASCO 2001, 20:351a.
Bakker ABH, Schreurs MWJ, de Boer AJ, et al.: Melanocyte lineage-specific antigen qp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med 1994, 179:1005–1009.
Wolfel T, van Pel A, Brichard V, et al.: Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur J Immunol 1994, 24:759–764.
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Agarwala, S.S. Intermediate- and high-risk melanoma. Curr. Treat. Options in Oncol. 3, 205–217 (2002). https://doi.org/10.1007/s11864-002-0010-7
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DOI: https://doi.org/10.1007/s11864-002-0010-7