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Melanoma Treatment (PDQ®)

Health Professional Version
Last Modified: 03/19/2014

Stage II Melanoma

Standard Treatment Options for Patients With Stage II Melanoma
Adjuvant Treatment Options for Patients With Stage II Melanoma
Treatment Options Under Clinical Evaluation for Patients With Stage II Melanoma
Current Clinical Trials

Stage II melanoma is defined by the American Joint Committee on Cancer's TNM classification system:[1]

  • T2b, N0, M0
  • T3a, N0, M0
  • T3b, N0, M0
  • T4a, N0, M0
  • T4b, N0, M0
Standard Treatment Options for Patients With Stage II Melanoma
  • Current evidence suggests that for melanomas with a thickness between 2 mm and 4 mm, the surgical margins need to be 2 cm or less.

    The Intergroup Melanoma Surgical Trial compared 2-cm margins versus 4-cm margins for patients with 1-mm thick melanomas to 4-mm thick melanomas. With a median follow-up of more than 10 years, no significant difference was observed between the two groups in terms of local recurrence or survival. The reduction in margins from 4 cm to 2 cm was associated with a statistically significant reduction in the need for skin grafting (46% to11%; P < .001) and a reduction in the length of the hospital stay.[2] Depending on the location of the melanoma, most patients can now have this surgery performed on an outpatient basis.

    A study conducted in the United Kingdom randomly assigned patients with melanomas more than 2 mm in thickness to excision with either 1 cm margins or 3 cm margins.[3] Patients treated with 1 cm margins of excision had a higher rate of local regional recurrence (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.00–1.59; P = .05), but no difference in survival was seen (HR, 1.24; 95% CI, 0.96–1.61; P = .1).

    This suggests that 1 cm margins may not be adequate for patients with melanomas that are more than 2 mm in thickness. Few data are available to guide treatment in patients with melanomas more than 4 mm thick; however, most guidelines recommend margins of 3 cm whenever anatomically possible. Although prophylactic regional lymph node dissections (LNDs) have been used in patients with stage II melanomas, four prospective randomized trials have failed to show a benefit for this procedure in terms of survival.[4-7]

    Lymphatic mapping and sentinel lymph node (SLN) biopsy have been used to assess the presence of occult metastasis in the regional lymph nodes of patients with stage II disease, which potentially identifies individuals who may be spared the morbidity of regional LND and individuals who may benefit from adjuvant therapy.[8-12] The diagnostic accuracy of SLN biopsy has been demonstrated in several studies with a false-negative rate of 0% to 2%.[8,13-17] Using a vital blue dye and a radiopharmaceutical agent, which are injected at the site of the primary tumor, the first lymph node in the lymphatic basin that drains the lesion can be identified, removed, and examined microscopically. If metastatic melanoma is detected, a complete regional lymphadenectomy can be performed in a second procedure. To ensure accurate identification of the SLN, lymphatic mapping and removal of the SLN should be performed prior to wide excision of the primary melanoma.

    To date, no published data from prospective trials are available on the clinical significance of micrometastatic melanoma in regional lymph nodes, but some evidence suggests that for patients with tumors of intermediate thickness and occult metastasis, survival is better among those patients who undergo immediate regional lymphadenectomy than it is among those who delay lymphadenectomy until the clinical appearance of nodal metastasis.[7] Because this finding arose from a post-hoc subset analysis of data from a randomized trial, it should be viewed with caution.

    The International Multicenter Selective Lymphadenectomy Trial (MSLT-1 [JWCI-MORD-MSLT-1193]) included 1,269 patients with intermediate-thickness (defined as 1.2 mm–3.5 mm in this study) primary melanomas.[18] There was no melanoma-specific survival advantage (the primary endpoint) for those patients randomly assigned to wide excision plus SLN biopsy followed by immediate complete lymphadenectomy for node positivity versus patients randomly assigned to nodal observation and delayed lymphadenectomy for subsequent nodal recurrence at a median of 59.8 months.[18][Level of evidence: 1iiB]

    This trial was not designed to detect a difference in the impact of lymphadenectomy in patients with microscopic lymph node involvement.[18]

Adjuvant Treatment Options for Patients With Stage II Melanoma
  • Adjuvant treatment after resection (e.g., with interferons) has not been shown to impact survival.
Treatment Options Under Clinical Evaluation for Patients With Stage II Melanoma
  • Clinical trials testing adjuvant treatment following surgery.
Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II melanoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

  1. Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44. 

  2. Balch CM, Urist MM, Karakousis CP, et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial. Ann Surg 218 (3): 262-7; discussion 267-9, 1993.  [PUBMED Abstract]

  3. Thomas JM, Newton-Bishop J, A'Hern R, et al.: Excision margins in high-risk malignant melanoma. N Engl J Med 350 (8): 757-66, 2004.  [PUBMED Abstract]

  4. 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 49 (11): 2420-30, 1982.  [PUBMED Abstract]

  5. Sim FH, Taylor WF, Ivins JC, et al.: A prospective randomized study of the efficacy of routine elective lymphadenectomy in management of malignant melanoma. Preliminary results. Cancer 41 (3): 948-56, 1978.  [PUBMED Abstract]

  6. Balch CM, Soong SJ, Bartolucci AA, et al.: Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg 224 (3): 255-63; discussion 263-6, 1996.  [PUBMED Abstract]

  7. Cascinelli N, Morabito A, Santinami M, et al.: Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet 351 (9105): 793-6, 1998.  [PUBMED Abstract]

  8. Gershenwald JE, Thompson W, Mansfield PF, et al.: Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 17 (3): 976-83, 1999.  [PUBMED Abstract]

  9. McMasters KM, Reintgen DS, Ross MI, et al.: Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement. J Clin Oncol 19 (11): 2851-5, 2001.  [PUBMED Abstract]

  10. Cherpelis BS, Haddad F, Messina J, et al.: Sentinel lymph node micrometastasis and other histologic factors that predict outcome in patients with thicker melanomas. J Am Acad Dermatol 44 (5): 762-6, 2001.  [PUBMED Abstract]

  11. Essner R: The role of lymphoscintigraphy and sentinel node mapping in assessing patient risk in melanoma. Semin Oncol 24 (1 Suppl 4): S8-10, 1997.  [PUBMED Abstract]

  12. Chan AD, Morton DL: Sentinel node detection in malignant melanoma. Recent Results Cancer Res 157: 161-77, 2000.  [PUBMED Abstract]

  13. Morton DL, Wen DR, Wong JH, et al.: Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127 (4): 392-9, 1992.  [PUBMED Abstract]

  14. Reintgen D, Cruse CW, Wells K, et al.: The orderly progression of melanoma nodal metastases. Ann Surg 220 (6): 759-67, 1994.  [PUBMED Abstract]

  15. Thompson JF, McCarthy WH, Bosch CM, et al.: Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res 5 (4): 255-60, 1995.  [PUBMED Abstract]

  16. Uren RF, Howman-Giles R, Thompson JF, et al.: Lymphoscintigraphy to identify sentinel lymph nodes in patients with melanoma. Melanoma Res 4 (6): 395-9, 1994.  [PUBMED Abstract]

  17. Bostick P, Essner R, Glass E, et al.: Comparison of blue dye and probe-assisted intraoperative lymphatic mapping in melanoma to identify sentinel nodes in 100 lymphatic basins. Arch Surg 134 (1): 43-9, 1999.  [PUBMED Abstract]

  18. Morton DL, Thompson JF, Cochran AJ, et al.: Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355 (13): 1307-17, 2006.  [PUBMED Abstract]