1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study

The trial management committee deemed that it was not appropriate to present any outcomes data related to the primary endpoints after 1 year of follow-up. The major clinical finding was that there was a significant increase in the use of reconstructive procedures between the two cohorts (Table 2). Overall, the rate of reconstruction was more than doubled in the 2-cm arm compared with the 1-cm arm (39.4 vs. 13.6%, respectively; p < 0.0001). The largest difference was seen in the head and neck region (1 cm: 8.3% vs. 2 cm: 68.8%; p = 0.002), although the subgroup sample size was small and the confidence intervals (CI) were wide; thus, the size of the difference needs to be interpreted with caution. Similarly, there was a large and significant difference in the incidence of reconstruction in the extremities. Clinically, these data are relevant, given the relative lack of tissue laxity in the extremities, the cosmetic implications of large excision margins in the head and neck region and the unique functional and anatomical considerations of both areas. It is interesting to note that only one prior RCT included patients with head and neck cutaneous melanoma, comprising only 0.3% (16/326) of cases in that particular study and < 0.02% of all participants in the pooled RCT evidence to date.22 Two of the previous RCTs reported a significantly increased need for reconstruction when comparing a 2-cm wider excision margin with a 4-cm margin. In the Scandinavian study, it was possible to close the wound directly in 69% of the 2-cm group, which is close to our findings (65.1%).5 In the Intergroup and the MSLT-1 studies, the overall reconstruction rates were 28 and 22% respectively, again similar to our own data.9,24 Haigh et al. performed a systematic review of all the available data at the time and estimated that the number needed to harm from a wider excision was 3 (95% CIs 2.38–3.7), indicating that for every three patients undergoing a wider excision, one patient would undergo a reconstruction who would otherwise not require it if a narrower margin had been used.25 In our dataset, the number needed to harm was calculated as 4.69 (95% CIs 3.45–8.1), indicating a substantial reconstructive burden that could be avoided with the use of a narrower 1-cm margin compared to a 2-cm margin.

Our QOL data yielded interesting and possibly surprising results. Ultimately there was no difference in quality of life or neuropathic pain data in any domain between the 1 and 2-cm groups. Similarly, there were no differences between the two margins in any subgroup analyses. One RCT QOL analysis was published from the UK BAPS/MSG study comparing 1 versus 3-cm margins for thicker melanoma.13 The wider margin was associated with a worse QOL initially, which normalised to baseline after 6 months. This was the case for both the mental and physical component scores of QOL tool employed. In our study, we noticed a significant worsening of the FACT-M melanoma surgery subscale, which persisted after 12 months (Fig. 2). Similarly, the emotional well-being subscale progressively improved over the 12-month postoperative period. The differences between our study and the U.K. BAPS/MSG study may be due to the different QOL tools used, although the improvement in emotional well-being may be representative of the improved multidisciplinary care and support most patients currently receive in major cancer centres.

We found that the surgical adverse event rate (AER) was nearly identical for both arms of the study: approximately 10–11%. The complication rate was the same between the two arms of the study except the wound necrosis/skin graft loss rate. We suggest that this is related to the increased rate of reconstruction in the 2-cm arm. The wide excision biopsy site surgical AER was 5.4 and 3.6% in the 1 and 2-cm groups, respectively. In comparison, the Intergroup trial demonstrated an approximate 5% complication rate at the primary site, regardless of margin.9 The Sunbelt Melanoma Trial demonstrated a 4.6% surgical AER at the sentinel node biopsy site, which is comparable to our data.26 Nearly all surgical AEs recorded in our study were grade I or II indicating that the procedures were performed to a uniformly high standard in the recruiting centres.

Our data indicate that the pilot study had a high rate of recruitment with the majority of potentially eligible patients declining participation rather than not being offered the trial. These are encouraging data and are likely to be due to both the permissive trial design, allowing patients to be recruited to subsequent trials upon progression or discovery of a positive sentinel node biopsy, and the relative lack of competing clinical trials for patients who are at the same stage of the disease. Furthermore, the successful completion of the pilot study indicates enthusiastic engagement by clinicians and consumer groups internationally who are keen to see the issue resolved for the benefit of future patients. A simple trial design with the experimental intervention representing a seemingly modest modification of the internationally accepted standard of care also lends itself greatly to successful recruitment.