Surgical excision margins for primary cutaneous melanoma: a Cochrane review

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Surgical excision margins for primary cutaneous
melanoma a Cochrane review

• Clinical

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Clinical question

• Does the width of the excision margins influence
  survival following surgery for primary cutaneous
  melanoma?

Source Sladden MJ, Balch C, Barzilai DA, Berg D,
Freiman A, Handiside T, Hollis S, Lens MB,
Thompson JF. Surgical excision margins for
primary cutaneous melanoma. Cochrane Database of
Systematic Reviews 2009, Issue 4. Art. No.
CD004835. DOI 10.1002/14651858.CD004835.pub2.
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Context

• Cutaneous melanoma accounts for 5 of skin
  cancers, but 75 of skin cancer deaths.
• Primary cutaneous melanoma is confined to the
  skin, with no evidence of spread elsewhere in the
  body.
• The only potentially curative treatment currently
  available is surgery.
• National guidelines provide some consistent
  generalisations regarding the width of excision
  margins, but offer slightly different advice.

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Current national guidelines for excision margins
for primary cutaneous melanoma
Breslow Thickness UK (2002) US (2009) Australian (2008) Swiss (2005) Dutch (2005) German (2008)
In-situ 2 to 5 mm 5 mm 5 mm 5 mm 5 mm 5 mm
1 mm 1 cm 1 cm 1 cm 1 cm 1 cm 1 cm
1.01 to 2 mm 1 to 2 cm 1 to 2 cm 1 to 2 cm 1 cm 1 cm 1 cm
2.01 to 4 mm 2 to 3 cm 2 cm 1 to 2 cm 2 cm 2 cm 2 cm
gt 4 mm 2 to 3 cm 2 cm 2 cm 2 cm 2 cm 2 cm
Margins may be modified to accommodate
individual anatomic or functional
considerations. Caution be exercised for
melanomas 2 to 4 mm thick, because evidence
concerning optimal excision margins is unclear.
Where possible, it may be desirable to take a
wider margin (2 cm) for these tumours depending
on tumour site and surgeon/patient preference.
www.cochranejournalclub.com
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Methods

• A Cochrane intervention review.
• Authors searched for eligible studies in the
  Cochrane Skin Group register, The Cochrane
  Central Register of Controlled Trials, MEDLINE
  and EMBASE up to August 2009.
• Hazard ratios (HR) were used for the primary
  analyses, summarising the average effect over 5
  and 10 years of follow up.
• Planned subgroup analysis by site of the melanoma
  and its thickness were not possible because of
  insufficient data.

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PICO(S) to assess eligible studies

• Participants All ages and all ethnic groups with
  primary cutaneous melanoma, of all Breslow
  thicknesses, confirmed histologically on biopsy
  and without metastases (AJCC/UICC Stage I and
  II). Patients diagnosed with in-situ melanoma
  (Stage 0) were not eligible.
• Intervention and Comparison Different widths of
  excision margins. Narrow and wide margins were
  not pre-defined.
• Outcomes include
• Time to death, and time to death or recurrence
• Quality of life
• Adverse effects (including surgical
  complications)
• Studies Randomized controlled trials.

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Description of eligible studies

• Five randomised controlled trials (RCTs),
  published in 11 reports, testing three different
  comparisons of excision margins
• 1 cm versus 3 cm (2 RCTs, 1603 participants)
• 2 cm versus 4 cm (1 RCT, 486 participants)
• 2 cm versus 5 cm (2 RCTs, 1326 participants)
• All trials reported analyses of death and
  recurrence, one trial reported on quality of life
  and two trials reported on adverse events.

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Results Deaths and recurrence

• Deaths from any cause
• Hazard Ratio for all deaths was non-significantly
  in favour of wider excision (1.04, 95 confidence
  interval 0.95 to 1.15).
• This is compatible with between about 6 fewer
  deaths per 1000 patients over ten years after
  narrow excision and 18 fewer deaths per 1000
  after wider excision.
• Recurrence or deaths from any cause
• Hazard ratio for recurrence or death was
  non-significantly in favour of wider excision
  (1.13, 95 confidence interval 0.99 to 1.28).

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Results Quality of life and adverse events

• Quality of life
• Patients treated with a 3 cm margin had
  significantly poorer physical and mental function
  than those in the 1 cm group one month after
  surgery. This difference was not apparent by six
  months.
• Those treated with a 3 cm margin had a poorer
  perception of their scar than those treated with
  a 1 cm margin.
• Adverse effects
• Skin grafts were reduced from 46 with 4 cm
  margins to 11 with 2 cm margins. This led to
  hospital stays that were shorter by 1 or 2 days.
• There was no significant difference in wound
  infection.

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Results Deaths from any cause
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Useful links

• Surgical excision margins for primary cutaneous
  melanoma (the Cochrane Review)
• Cochrane Journal Club discussion points
• Cochrane Handbook for Systematic Reviews of
  Interventions
• Chapter 7.7.6  Data extraction for time-to-event
  outcomes
• Chapter 9.2.6  Effect measures for time-to-event
  (survival) outcomes
• ParmarMK, Torri V, Stewart L. Extracting summary
  statistics to perform meta-analyses of the
  published literature for survival endpoints.
  Statistics in Medicine 199817(24)281534.
• Williamson PR, Smith CT, Hutton JL, Marson AG.
  Aggregate data meta-analysis with time-to-event
  outcomes. Statistics in Medicine
  200221(22)333751