Summary of Melanoma Trials
Margins
WHO Melanoma trial evaluated 612 patients with melanomas less than 2 mm thick
who underwent 1-versus 3-cm radial excision margins.
There were no local recurrences in patients with lesions less 1 mm thick regardless of
surgical margins, and survival was not different between the narrow- and wide-excision
groups.
Although the rate of local recurrence was not statistically different between the two
groups, five of the six local recurrences observed in this trial occurred in patients with
lesions between 1 and 2 mm thick who were treated with 1-cm excisions. On the basis of
these data, the authors of this trial concluded that a 1-cm margin for melanomas less
than 2 mm thick was safe.
Others have been reluctant to accept these recommendations for patients with 1- to 2mm thick melanomas because of the trend toward higher local recurrence rates in this
subgroup.
The Intergroup Melanoma Surgical Trial addressed the issue of surgical margins for
intermediate thickness melanomas. This study randomized 486 patients with melanomas
1 to 4 mm thick to undergo 2- versus 4-cm margins of excision. No statistically
significant differences in survival rate, local recurrence rate, or intransit metastases were
noted between these groups.
UK Melanoma Study Group - 900 patients with >2mm thickness enrolled, 453 were
randomly assigned to undergo surgery with a 1-cm margin of excision and 447 with a 3cm margin of excision. A 1-cm margin of excision for melanoma with a poor prognosis
(as defined by a tumor thickness of at least 2 mm) is associated with a significantly
greater risk of regional recurrence than is a 3-cm margin, but with a similar overall
survival rate.
Sentinel Lymph Node Biopsy
20% of clinical negative nodes will have pathologic nodes
20% of clinical positive nodes will have pathologic negative nodes (dependent on tumor
thickness)
Requires learning curve caseload of 25-50 cases
Should have >97% chance of successfully finding sentinel node
7-35% will have other positive nonsentinel nodes following CLND
A recent multicenter study showed the histologic status of the sentinel node to be a more
important prognostic factor than tumor thickness in patients with clinically negative
nodes before sentinel node biopsy.
MSLT-1 prelim results – melanoma >1mm or Clark>III
Positive SNB+immediate CLND vs delayed CLND – not significant
Positive SNB+immediate CLND vs delayed CLND – significantly prolongs overall
disease-free survival
SNB has prognostic significance
Accurately identifies occult nodal mets which will grow to palpable size if managed by
watch and wait
Prolongs survival after immediate CLND for pSNB vs delayed CLND (by 20%)
Adjuvant Therapy
Eastern Cooperative Oncology Group (ECOG) trial 1684 -comparing a 1-year course
of high-doseadjuvant interferon-a-2b with observation in a randomized group of Stage
III 287 patients( melanomas .4.0 mm thick and patients with surgically resected regional
nodal metastases.)
There were statistically significant improved 5-year relapse-free survival rates (37 versus
26 percent) and overall survival rates (46 versus 37 percent) in the high-dose interferon
group compared with untreated patients. This study is currently the only trial to show an
overall survival benefit for any regimen in the adjuvant treatment of melanoma.
Patients with other forms of lymphatic metastases, such as local recurrences,
extracapsular nodal disease, intransit metastases, and satellite nodules, were excluded
from this study. The role of adjuvant interferon in this population of patients is
unknown.
ECOG trial 1690 was a three arm study comparing the same high-dose interferon
regimen used in ECOG trial 1684 with a low-dose interferon regimen and an observation
arm. At a median follow-up of 52 months, preliminary analysis confirmed the relapsefree survival benefit for the high-dose interferon regimen but did not show an overall
survival benefit. The low-dose treatment arm showed no significant benefit for either
relapse-free or overall survival.