Margins in Melanoma: Enough is Enough
Margins in Melanoma: Enough is Enough
Abstract & Commentary
Synopsis: The authors retrospectively studied 1155 patients with melanoma to determine the optimum excision margins. They recommend 1 cm for tumors smaller than 1 mm, 1.5 cm for tumors 1.01-2.00 mm, and 2 cm for tumors larger than 2 mm.
Source: Ng A, et al. Brit J Surg 2001;88:137-142.
To determine the relationship between excision margins and local recurrence, Ng and colleagues retrospectively studied 1155 patients who were treated for melanoma at the Auckland Melanoma Unit in New Zealand. The primary melanoma lesions were separated into five groups by 1 mm increments (0-1 mm, 1-2 mm, etc.) and the excision margins were stratified by 0.5 cm intervals. Local recurrence was defined as a recurrence within 5 cm of the scar. About one-half of the local recurrences were accompanied by simultaneous regional or distant metastases.
For each thickness group, a regression analysis was performed to study the relationship between the local recurrence rate and the excision margin. The regression analysis was then used to determine the predicted minimum excision margin, termed the "optimum margin." If the surgical margins met or exceeded the optimum margin, the predicted local recurrence rate would be zero. The optimum margins were found to be 1 cm for tumors smaller than 1 mm, 1.5 cm for tumors 1.01-2.00 mm, and 2 cm for tumors larger than 2 mm.
Ng et al then applied these "optimum margins" to the entire group of patients. There was a statistically significant difference in the recurrence rate between optimally and suboptimally resected melanomas for each thickness group with the exception of lesions more than 4 mm thick. Even mortality was strongly influenced by appropriate excision margins with a P value of less than 0.03 for each thickness group, except tumors larger than 4 mm (P = 0.11). The importance of local control is suggested by the fact that 39% of patients with a local recurrence died compared with 8% without a local recurrence.
COMMENT by Kenneth W. Kotz, MD
With the incidence of melanoma rapidly increasing in the United States, defining the most appropriate surgical margins is of critical importance. Based on retrospective data on more than 1000 patients, Ng et al provide specific recommendations for resection margins in primary melanoma: 1, 1.5 and 2 cm for less than 1, 1.01-2 and more than 2 mm lesions, respectively.
In general, recommendations regarding the most appropriate surgical margins have been based on a number of retrospective and several prospective randomized trials. This has led to a general consensus for the following approach: 0.5 cm margins for melanoma in situ, 1 cm margins for melanoma less than 1 cm and 2 cm margins for melanoma 2-4 mm,1-3 conclusions also reached by Ng et al. Unfortunately, there remains some controversy regarding those lesions over 4 mm and those with a depth of 1-2 mm.
For more than 4 mm lesions, Ng et al found the "optimum margin" to be 2 cm. Unfortunately, randomized data for these thick melanomas is lacking. Nevertheless, most authors have similar approaches, such as "at least a 2 cm margin,"3 a "2 cm margin,"1 and text stating, "it appears that the 2 cm margin can be safely applied" with the table stating "> 2 cm" margins.2
For 1-2 mm lesions, 2 cm margins are frequently advocated.1-3 This is based in part on the World Health Organization trial which randomized 612 patients with melanomas less than 2 mm thick to 1 or 3 cm margins.4 There were four local recurrences among the cases with 1.1-2.0 mm lesions treated with 1 cm margins vs. none for the 3 cm group. While this local recurrence rate was not statistically different, and there were no differences in disease-free or overall survival either, there remains enough of a concern that 2 cm margins continue to be widely used. Ng et al recommend margins of 1.5 cm for this group of patients. Although the study by Ng et al lacks the benefits of a prospective randomization, the wide variation in regional surgical techniques provided the advantage of being able to study a range of margins.
Because both biologic factors as well as appropriate surgical margins are likely to contribute to the risk of a local relapse,2 there will not be any margin above which the local recurrence rate will be zero. For example, there was still a local recurrence rate of 2.3% for lesions 1.0-2.0 mm in a trial of 742 patients randomized to either 2 or 4 cm margins.5 Even so, care should be taken before universally adopting smaller margins because of the potentially devastating consequences of a local recurrence. On the other hand, one must also consider the long-term morbidity of the larger surgical margins, a factor not easily amenable to research, particularly in a retrospective study. Therefore, while 2 cm remains a standard for 1-2 mm melanomas, those patients requiring smaller margins for anatomical or medical considerations can be reassured that they still have an extremely low local recurrence rate.
References
1. Lotze M, et al. In: DeVita VT, et al, eds. Cancer: Principles and Practice of Oncology Vol. 2, 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2001.
2. Ross M, et al. In: Balch C, et al, eds. Cutaneous Melanoma, 3rd ed. St. Louis, Mo: Quality Medical Publishing; 1998.
3. Margolin K, et al. In: Padzur R, et al, eds. Cancer Management: A Multidisciplinary Approach, 4th ed. Melville, NY: Publisher Research & Representation, Inc, 2000.
4. Veronesi U, et al. Arch Surg 1991;126:438-441.
5. Karakousis C, et al. Ann Surg Onc 1996;3:446-452.
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