Trial of Surgical Excision Margins in Thick Primary Melanoma
Primary Purpose
Melanoma, Surgery, Treatment Outcome
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
2-cm margin
4-cm margin
Sponsored by

About this trial
This is an interventional treatment trial for Melanoma focused on measuring Melanoma/mortality/pathology/*surgery, Randomized Controlled Trials as Topic, Survival, Disease-Free Survival
Eligibility Criteria
Inclusion Criteria:
- Melanoma >2 mm
- Age ≤ 75 yr
- Patients operated on with ≤ 2-cm at diagnosis
- Final surgery planned within 8 weeks after date of diagnosis
- Patient fit for surgery
- Signed patient consent form
Exclusion Criteria:
- Melanoma on hand, foot, head-neck or ano-genital regions
- The presence of in-transit- regional and/or distant spread of the disease
- Illness making patient unfit for surgery
- Previous malignancies except basal cell- and in-situ colli uteri cancer
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
2 cm margin of excision
4 cm margin of excision
Arm Description
Patients with CMM >2 mm treated with an excision of 2-cm.
Patients with CMM >2 mm treated with an excision of 4-cm.
Outcomes
Primary Outcome Measures
Overall survival
Secondary Outcome Measures
Recurrence free survival
Full Information
NCT ID
NCT01183936
First Posted
August 17, 2010
Last Updated
August 17, 2010
Sponsor
Karolinska Institutet
Collaborators
Swedish Cancer Society, Stockholm Cancer Society
1. Study Identification
Unique Protocol Identification Number
NCT01183936
Brief Title
Trial of Surgical Excision Margins in Thick Primary Melanoma
Official Title
A Randomised Trial of Surgical Excision Margins for Thick Primary Cutaneous Melanoma (>2 mm). A Multicenter Trial Comparing 2-cm vs 4-cm
Study Type
Interventional
2. Study Status
Record Verification Date
June 1991
Overall Recruitment Status
Completed
Study Start Date
January 1992 (undefined)
Primary Completion Date
May 2004 (Actual)
Study Completion Date
December 2006 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Karolinska Institutet
Collaborators
Swedish Cancer Society, Stockholm Cancer Society
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Objectives: The purpose of this study was to assess the effects of an excision margin of 2 cm versus 4 cm for patients with primary cutaneous malignant melanoma (CMM).
Study hypothesis: The hypothesis is that there is no difference between the two treatment arms measured as overall survival and recurrence free survival.
Detailed Description
Traditionally CMM have been excised with wide resection margins of 5-cm (sometimes with 10-cm towards the local lymph node basin) with the radical removal of lymph nodes. This treatment emerged from a recommendation from Handley in 1907 based on a single pathological specimen. This "radical" surgical management resulted in bad cosmetic results, lymph oedema, long hospital inpatient stay, frequent skin grafting and/or complicated skin flap reconstructions. Not until some 60-plus years later did questions arise in clinical practices whether the need for this extensive surgery was mandated and clinical practice was not substantially changed until the late 1980's. Retrospective studies published in the 1980s suggested that narrower excision margins may be appropriate for treatment of some CMMs, especially thinner lesions.
Breslow tumour thickness of the CMM is the most important prognostic indicator of localised disease and is therefore the information upon which today's surgical strategies are founded. However, recommendations vary over the world especially for thicker tumors. For CMM of ≤ 1 mm thickness most centers use a 1 cm margin, but for tumours 1.01 - 4 mm the margins of resection are 1-3 cm depending on the country. Most patients with CMM > 4 mm are operated on with a margin of 2-cm today. The different national guidelines are thus, somewhat confusing and in a report from 2004 Thomas showed that a 1-cm margin for CMM with a poor prognosis (≥2 mm) is associated with a greater risk of regional recurrence than in a 3-cm margin, but with a similar survival rate.
Still, quite sound evidence now exists to state that narrower excisions - for thinner tumors - is as safe as more wide surgery. To date, five published randomised trials (11 reports) have been published to access what type of surgery to recommend in the different prognostic groups but despite this effort there are still controversies. In a report by Lens based on 4 randomised trials the authors concluded that current evidence was not sufficient to address the optimal surgical margins for all CMM. Furthermore the Cochrane report from 2009 states; "Current randomised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma". However, the studies were not designed to access "optimal" surgery, they were designed to compare one surgical strategy with another, where after the results have been interpreted into clinical guidelines.
In conclusion there is a need for additional studies and further research is required especially for the patients with poorer prognoses, i.e. with tumors >2 mm.
In 1992 a multicenter trial was launched from the Swedish Melanoma Study Group. The 936 patients in the study were included from January 22 1992 to May 19 2004. Patients were recruited from Sweden ( 6 centres with 644 pat), Denmark (180 pat), Estonia (80 pat) and Norway (32 pat). Randomisation routines were set up by the steering committee and eligible patients were randomised locally by telephone calls to national and international cancer centres (upon a histologically proven diagnoses and signed patient consent form). Only patients with a CMM >2 mm and with localised disease (who fulfilled the in- and exclusion criteria) were eligible for study inclusion. Patients with CMM on the hands, feet, head-neck and ano-genital region were excluded. Final surgery must had been planned within 8 weeks after date of diagnosis. All analyses were conducted according to the intention-to-treat principle.
Patients were followed clinically every 3 months for 2 years and thereafter every 6 months up to 5 years. Follow-up data was thus collected from cancer registries, cause of death registries and medical records. The overall mean follow-up time was 6 years and 9 months (6 years and 7 months vs. 6 years and 10 months).
Statistical analyses were made by Kaplan Meier life-table curves. Prognostic factors was assessed with the use of a uni- and multivariate Cox regression analysis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma, Surgery, Treatment Outcome
Keywords
Melanoma/mortality/pathology/*surgery, Randomized Controlled Trials as Topic, Survival, Disease-Free Survival
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
936 (Actual)
8. Arms, Groups, and Interventions
Arm Title
2 cm margin of excision
Arm Type
Active Comparator
Arm Description
Patients with CMM >2 mm treated with an excision of 2-cm.
Arm Title
4 cm margin of excision
Arm Type
Active Comparator
Arm Description
Patients with CMM >2 mm treated with an excision of 4-cm.
Intervention Type
Procedure
Intervention Name(s)
2-cm margin
Intervention Description
Patients with CMM treated with a surgical safety margin of 2-cm in the surrounding skin and down to the fascia.
Intervention Type
Procedure
Intervention Name(s)
4-cm margin
Intervention Description
Patients with CMM treated with a surgical safety margin of 4-cm in the surrounding skin and down to the fascia.
Primary Outcome Measure Information:
Title
Overall survival
Secondary Outcome Measure Information:
Title
Recurrence free survival
10. Eligibility
Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Melanoma >2 mm
Age ≤ 75 yr
Patients operated on with ≤ 2-cm at diagnosis
Final surgery planned within 8 weeks after date of diagnosis
Patient fit for surgery
Signed patient consent form
Exclusion Criteria:
Melanoma on hand, foot, head-neck or ano-genital regions
The presence of in-transit- regional and/or distant spread of the disease
Illness making patient unfit for surgery
Previous malignancies except basal cell- and in-situ colli uteri cancer
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulrik Ringborg, M.D., Ph.D.
Organizational Affiliation
Dept of Oncology-Pathology, Karolinska Institute
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
22027547
Citation
Gillgren P, Drzewiecki KT, Niin M, Gullestad HP, Hellborg H, Mansson-Brahme E, Ingvar C, Ringborg U. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial. Lancet. 2011 Nov 5;378(9803):1635-42. doi: 10.1016/S0140-6736(11)61546-8. Epub 2011 Oct 23. Erratum In: Lancet. 2011 Nov 5;378(9803):1626.
Results Reference
derived
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Trial of Surgical Excision Margins in Thick Primary Melanoma
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