Surgical excision margins for primary cutaneous melanoma

Abstract

Background

Cutaneous melanoma accounts for 75% of skin cancer deaths. Standard treatment is surgical excision with a safety margin some distance from the borders of the primary tumour. The purpose of the safety margin is to remove both the complete primary tumour and any melanoma cells that might have spread into the surrounding skin.

Excision margins are important because there could be trade‐off between a better cosmetic result but poorer long‐term survival if margins become too narrow. The optimal width of excision margins remains unclear. This uncertainty warrants systematic review.

Objectives

To assess the effects of different excision margins for primary cutaneous melanoma.

Search methods

In August 2009 we searched for relevant randomised trials in the Cochrane Skin Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2009), MEDLINE, EMBASE, LILACS, and other databases including Ongoing Trials Registers.

Selection criteria

We considered all randomised controlled trials (RCTs) of surgical excision of melanoma comparing different width excision margins.

Data collection and analysis

We assessed trial quality, and extracted and analysed data on survival and recurrence. We collected adverse effects information from included trials.

Main results

We identified five trials. There were 1633 participants in the narrow excision margin group and 1664 in the wide excision margin group. Narrow margin definition ranged from 1 to 2 cm; wide margins ranged from 3 to 5 cm. Median follow‐up ranged from 5 to 16 years.

Authors' conclusions

This systematic review summarises the evidence regarding width of excision margins for primary cutaneous melanoma. None of the five published trials, nor our meta‐analysis, showed a statistically significant difference in overall survival between narrow or wide excision.

The summary estimate for overall survival favoured wide excision by a small degree [Hazard Ratio 1.04; 95% confidence interval 0.95 to 1.15; P = 0.40], but the result was not significantly different. This result is compatible with both a 5% relative reduction in overall mortality favouring narrower excision and a 15% relative reduction in overall mortality favouring wider excision. Therefore, a small (but potentially important) difference in overall survival between wide and narrow excision margins cannot be confidently ruled out.

The summary estimate for recurrence free survival favoured wide excision [Hazard Ratio 1.13; P = 0.06; 95% confidence interval 0.99 to 1.28] but again the result did not reach statistical significance (P < 0.05 level).

Current randomised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma.

Author(s)

Michael J Sladden, Charles Balch, David A Barzilai, Daniel Berg, Anatoli Freiman, Teenah Handiside, Sally Hollis, Marko B Lens, John F Thompson

Abstract

Plain language summary

Surgical excision margins for primary cutaneous melanoma

Whilst melanoma accounts for only 5% of skin cancers, it is important because it is the cause of 75% of all skin cancer deaths. For primary cutaneous melanoma, standard treatment is complete surgical removal of the melanoma with a safety margin some distance from the visible edges of the primary tumour. The purpose of the safety margin is to remove both the primary tumour and any melanoma cells that might have spread into the surrounding skin. However, the optimal width of the safety (excision) margin remains unclear.

This systematic review summarises the evidence about how much tissue (safety margin) should be removed for primary cutaneous melanoma (skin cancer). Excision margins are important because there could be a trade‐off between a better cosmetic result but poorer long‐term survival if excision margins become too narrow.

It is important to note that for the purposes of this review we consider only invasive melanoma ‐ that has invaded into the deeper layer of the skin (dermis) ‐ and not melanoma‐in‐situ where the melanoma cells are confined to the outermost layer of the skin (epidermis).

We found five published randomised trials, none of which showed a statistically significant difference in overall survival for patients who had either narrow or wide removal of the melanoma and surrounding tissue.  Similarly, our meta‐analysis showed there was no statistically significant difference in overall survival between the two groups treated with either narrow or wide excision. 

The summary estimate for overall survival favoured wide excision by a small degree, but the result was not significantly different. This result is compatible with both a 5% relative reduction in overall mortality favouring narrower excision and a 15% relative reduction in overall mortality favouring wider excision. 

Current randomised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma.

Author(s)

Michael J Sladden, Charles Balch, David A Barzilai, Daniel Berg, Anatoli Freiman, Teenah Handiside, Sally Hollis, Marko B Lens, John F Thompson

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

None of the individual trials, nor our meta‐analysis, has shown a statistically significant difference in overall survival between the two groups that were treated with narrow or wide excision margins. Current randomised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma.

Despite this, however, numerous expert international committees have produced fairly consistent guidelines for melanoma excision margins.

It is important to determine whether the absence of any statistically significant overall survival difference in randomised studies (or meta‐analyses thereof) conducted to date preclude the possibility that there may actually be a real but very small difference in survival for different margin widths (Johnson 2004). So far this question remains unanswered. There is a potential for causing harm if excision margins become excessively narrow. Narrow excision margins reduce surgical morbidity and complications, and the need for general anaesthesia, but should only be used if cure is not compromised.

Implications for research 

Further randomised trials would be needed to clarify optimal excision margins for primary cutaneous melanoma. Any future trials should be appropriately designed and powered to determine whether different subsets of Breslow thickness can be treated with different excision margins and, if so, the minimum optimal margins.

Current data suggest that 'narrow' margins produce similar outcomes to 'wider' margins so perhaps trials should compare different degrees of narrow excision margin, for example 1 versus 2 cm. However, an extremely large study would be required to demonstrate a lack of important difference between these different excision margins, because only a very small survival deficit (if any) would be acceptable. Similarly, a prospective trial for facial melanomas, perhaps comparing 0.5 cm and 1.0 cm excision margins, would be clinically very useful, but would likely require huge numbers of participants and resources.

In future trials, primary outcomes should focus on overall survival and report number of events. Authors should provide clear and consistent definitions of 'recurrences'. All trials should include and assess quality of life outcomes.

Individual patient data meta‐analysis could be helpful in further investigating the impact of Breslow thickness on excision margins.

Access to detailed outcome data, broken down by Breslow thickness, would enhance the quality of future meta‐analyses. This might improve the quality of treatment recommendations and subsequent care, and help researchers focus on the most appropriate clinical questions.

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