Wider surgical margins needed for thicker primary cutaneous melanoma

A narrow excision margin appeared to increase risk for melanoma-specific death among patients with cutaneous melanoma on the trunk and/or limbs with a Breslow thickness greater than 2 mm, according to findings of a randomized, open-label multicenter trial.

“This long-term survival analysis of a randomized trial of 1 cm vs. 3 cm excision margins for melanomas greater than 2 mm in thickness has shown that a 1 cm margin is detrimental to a 3 cm margin in terms of melanoma-specific survival,” Andrew J. Hayes, MA(Oxon), MBBS, FRCS (Gen), PhD, a consultant general surgeon and surgical oncologist at the Royal Marsden Hospital National Health Foundation Trust in London, told HemOnc Today. “Although this did not translate into a significant effect in OS in this cohort, this result will be particularly pertinent to younger patients for whom the competing effects of death from other causes will be less.”

Previous data from the current trial — evaluated after a median follow-up of 5 years — showed narrow excision margins increased the frequency of locoregional relapse, without significantly affecting OS, among patients with thick cutaneous melanomas.

In the current analysis, Hayes and colleagues examined long-term follow-up data from the trial to present additional survival data.

The analysis included data from 900 patients enrolled on the trial between Dec. 16, 1992 and May 22, 2001. All patients had one primary cutaneous melanoma greater than 2mm in Breslow thickness on the trunk or limbs (excluding palms or soles of the feet). Researchers randomly assigned patients to surgery with a 1 cm excision margin (n = 453) or a 3 cm margin (n = 447).

After a median follow-up of 8.8 years (106 months; range, 76-135 months), 494 patients died.

Although a higher number of overall deaths occurred in the 1-cm vs. 3-cm arm (253 vs. 241), this difference was not statistically significant.

Of the 359 melanoma-specific deaths, 194 occurred in the 1-cm group and 165 occurred in the 3-cm group (HR = 1.24; 95% CI, 1.01-1.53).

The estimated absolute difference in melanoma-specific survival at 10 years between the two groups was 5.95% (95% CI, –0.54 to 12.44).

Because death certificates were not obtained for non-U.K. patients, researchers conducted a sensitivity analysis of only U.K. patients (n = 338 in the 1 cm arm; n = 392 in the 3 cm arm). Results appeared comparable to the primary analysis (HR for OS = 1.11; 95% CI, 0.92-1.33; HR for melanoma-specific survival = 1.21; 95% CI, 0.97-1.5).

Taking into account the effect of death by other causes, the cumulative incidence of death from melanoma at 8.8 years was higher in the 1-cm group (47.9%; 95% CI, 42.8-53.2) than the 3-cm group (38.1%; 95% CI, 33.3-43.4).

Surgical complications occurred in 8% of the patients in the 1-cm group and 15% of the patients in the 3-cm group. The most common complications were partial or complete graft loss (1 cm, 2%; 3 cm, 4%) and wound dehiscence (1 cm, 2%; 3 cm, 2%).

“Most current guidelines presently advise a 2 cm margin for melanomas greater than 2 mm and prior randomized studies have shown that this is equivalent to a 4 cm margin in terms of melanoma specific survival,” Hayes said. “Hence, the clinical relevance of this study may relate to melanomas less than 2 mm in thickness but with adverse prognostic features such as ulceration and a high mitotic rate, for which a 1 cm margin is still presently advised.”

Hayes added that this is an area under investigation in an ongoing randomized trial known as MelmarT. – by Anthony SanFilippo

For more information:

Andrew J. Hayes, MA( Oxon), MBBS, FRCS (Gen), PhD, can be reached at andrew.hayes@rmh.nhs.uk

Disclosure: The researchers report no relevant financial disclosures.