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Guideline Summary
Guideline Title
Primary excision margins and sentinel lymph node biopsy in clinically node-negative cutaneous melanoma of the trunk or extremities: guideline recommendations.
Bibliographic Source(s)
Wright F, Spithoff K, Easson A, Murray C, Toye J, McCready D, Petrella T, Melanoma Disease Site Group. Primary excision margins and sentinel lymph node biopsy in clinically node-negative cutaneous melanoma of the trunk or extremities: guideline recommendations. Toronto (ON): Cancer Care Ontario (CCO); 2010 May 17. 38 p. (Evidence-based series; no. 8-2).  [56 references]
Guideline Status

This is the current release of the guideline.

The EVIDENCE-BASED SERIES report, initially the full original Guideline, over time will expand to contain new information emerging from their reviewing and updating activities.

Please visit the Cancer Care Ontario Web site External Web Site Policy for details on any new evidence that has emerged and implications to the guidelines.

Scope

Disease/Condition(s)

Truncal or extremity early-stage (clinically node-negative) cutaneous melanoma

Guideline Category
Assessment of Therapeutic Effectiveness
Treatment
Clinical Specialty
Dermatology
Family Practice
Geriatrics
Internal Medicine
Oncology
Pathology
Surgery
Intended Users
Advanced Practice Nurses
Physician Assistants
Physicians
Guideline Objective(s)
  • To evaluate what the optimal primary margins are of excision for clinically node-negative cutaneous melanoma that is a) in situ, b) <1 mm, c) 1 to 2 mm, d) 2 to 4 mm, or e) >4 mm
  • To evaluate if patients with clinically node-negative cutaneous melanoma that is a) in situ, b) <1 mm, c) 1 to 2 mm, d) 2 to 4 mm, or e) >4 mm should undergo sentinel lymph node biopsy (SLNB)
Target Population

Adult patients with truncal or extremity early-stage (clinically node-negative) cutaneous melanoma

Interventions and Practices Considered
  1. Narrow versus wide excision margins
  2. Wide excision plus sentinel lymph node biopsy (SLNB) followed by immediate completion lymphadenectomy (CLND) versus wide excision and postoperative observation with CLND at nodal recurrence
Major Outcomes Considered
  • Local and regional recurrence
  • Overall survival
  • Disease-free survival
  • Morbidity

Methodology

Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Literature Search Strategy

The MEDLINE and EMBASE databases were searched from 2002 to April week 3 2010 to identify evidence-based clinical practice guidelines on excision margins or sentinel lymph node biopsy (SLNB) for melanoma. In MEDLINE, the Medical Subject Heading (MeSH) terms "exp melanoma" or "exp skin neoplasms" were used and results were limited to the following publication types: consensus development conference, guideline, or practice guideline. In EMBASE, the MeSH terms "exp melanoma" or "exp skin tumours" were combined with "exp practice guidelines" and further limited by title keywords for melanoma and skin tumours to increase specificity. (See Appendix 1 in the original guideline document for the complete search strategies.)

The National Guideline Clearinghouse (http://www.guideline.gov/ External Web Site Policy) and Canadian Medical Association (CMA) Infobase (http://www.cma.ca/index.cfm/ci_id/54316/la_id/1.htm External Web Site Policy) websites were also searched for relevant guidelines using the keyword "melanoma". In addition, websites for the following guideline development organizations were searched: National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), National Health and Medical Research Council, New Zealand Guidelines Group, BC Cancer Agency, Alberta Cancer Board, Saskatchewan Cancer Agency, Cancer Care Manitoba, and Cancer Care Nova Scotia.

Guideline Selection Criteria

Evidence-based guidelines were included if they met the following criteria:

  • Provided recommendations on primary excision margins and/or SLNB for adult patients with early-stage cutaneous melanoma.
  • Described a systematic literature search process to identify evidence on which to base recommendations.
  • Published in English, due to the unavailability of translation services.
  • Published in 2002 or later.

Updated Literature Search Strategy

The literature search strategies for excision margins and SLNB used by the Australian Cancer Network/New Zealand Guidelines Group (AUS/NZ) guideline were modified where necessary and updated to April, week 3, 2010. The following databases were searched: MEDLINE, EMBASE, Cochrane Library, and ASCO Annual Meeting Proceedings. (See Appendix 1 in the original guideline document for the search strategies.)

Updated Literature Search Selection Criteria

Excision Margins

Studies were included if they met the following criteria:

  • Randomized controlled trials (RCTs) of adult patients with cutaneous melanoma comparing wide vs. narrow excision margins. Syntheses of evidence from RCTs in the form of systematic reviews or meta-analyses were also included. Abstract reports of RCTs or meta-analyses were included unless they reported results from preliminary analyses.
  • Reported on at least one of the following outcomes: local or regional recurrence, overall survival, disease-free survival, morbidity, quality of life.
  • Published in English, due to unavailability of translation services.
  • Published in April 2006 or later.

Sentinel Lymph Node Biopsy

Studies were included if they met the following criteria:

  • Comparative studies (randomized or non-randomized) comparing outcomes of interest for patients undergoing SLNB versus patients not undergoing SLNB, or non-comparative prospective or retrospective studies including ≥50 patients who underwent SLNB.
  • Reported on at least one of the following outcomes: local or regional recurrence, overall survival, disease-free survival, morbidity, quality of life.
  • Published in English, due to unavailability of translation services.
  • Published in May 2008 or later.
Number of Source Documents

Four evidence-based guidelines were identified that met the inclusion criteria.

Updated Literature Search Results

Excision Margins

One report of an updated meta-analysis and one other meta-analysis were identified that met the inclusion criteria.

Sentinel Lymph Node Biopsy

One article met the inclusion criteria.

Methods Used to Assess the Quality and Strength of the Evidence
Expert Consensus (Committee)
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence

Quality Appraisal of Guidelines

The Melanoma Disease Site Group (DSG) formed a working group to review and assess the clinical practice guidelines identified in the systematic search. The working group consisted of five clinicians with expertise in the surgical management of cutaneous melanoma and one methodologist. Working group members assessed the guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Assessments were collected and collated by one panel member (KS).

The AGREE instrument consists of six domains assessing guideline quality: 1) scope and purpose, 2) stakeholder involvement, 3) rigour of development, 4) clarity of presentation, 5) applicability, and 6) editorial independence. Each domain consists of a number of items addressing that particular aspect of guideline quality. The guideline is rated on each item using a scale from one (strongly disagree) to four (strongly agree). Agreement between reviewers consists of a difference between the highest and lowest scores of no more than one point on the scale, and disagreement exists when scores differ by 2 or more points.

Adoption of Evidence-based Guidelines

The AGREE domain scores for each evidence-based guideline identified in the systematic search were reviewed by the working group. The domain scores and overall assessment of guideline applicability were used as the basis for selection of a single evidence-based guideline for adoption. The guideline development group of the selected guideline was contacted to obtain additional information, including literature search strategies and study selection criteria.

Following the review of additional primary studies published since the search endpoint of the selected evidence-based guideline, the working group discussed each of the relevant recommendations within the guideline to determine whether they were appropriate given the available evidence and whether they should be applied in the context of Ontario. Individual recommendations were adopted as written.

Updated Literature Search

Quality Appraisal Results and Selection of Guideline for Adoption

The quality of the four evidence-based guidelines was appraised using the AGREE instrument. Results are reported in Table 1 in the original guideline document. The working group reviewed the suitability of each guideline for adaptation, with consideration of the AGREE ratings, the currency of the evidence review, and the applicability of the guideline for the purpose of answering the research questions. Working group members agreed that the Australia and New Zealand (AUS/NZ) guideline was most suitable for adoption.

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

Not stated

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

Report Approval Panel

Prior to the submission of this evidence-based series (EBS) draft report for external review, the report was reviewed and approved by the Program in Evidence-Based Care (PEBC) Report Approval Panel, which consists of two members, including an oncologist, with expertise in clinical and methodology issues.

External Review by Ontario Clinicians and Other Experts

The PEBC external review process is two-pronged and includes a targeted peer review that is intended to obtain direct feedback on the draft report from a small number of specified content experts and a professional consultation that is intended to facilitate dissemination of the final guidance report to Ontario practitioners.

Following the review and discussion of Section 1: Recommendations and Section 2: Evidentiary Base in the original guideline document of this EBS and the review and approval of the report by the PEBC Report Approval Panel, the Melanoma Disease Site Group (DSG) circulated Sections 1 and 2 to external review participants for review and feedback.

Methods

Targeted Peer Review

During the guideline development process, three targeted peer reviewers from Ontario and Alberta considered to be clinical and/or methodological experts on the topic were identified by working group. Several weeks prior to completion of the draft report, the nominees were contacted by email and asked to serve as reviewers. Three reviewers agreed, and the draft report and a questionnaire were sent via email for their review. The questionnaire consisted of items evaluating the methods, results, and interpretive summary used to inform the draft recommendations and whether the draft recommendations should be approved as a guideline. Written comments were invited. The questionnaire and draft document were sent out on February 9, 2010. Follow-up reminders were sent at two weeks (email) and at four weeks (telephone call). The working group from the Melanoma DSG reviewed the results of the survey.

Professional Consultation

Feedback was obtained through a brief online survey of healthcare professionals who are the intended users of the guideline. All plastic surgeons, general surgeons, head and neck surgeons, gynecological oncologists, and dermatologists in the PEBC database were contacted by email to inform them of the survey. Participants were asked to rate the overall quality of the guideline (Section 1) and whether they would use and/or recommend it. Written comments were invited. Participants were contacted by email and directed to the survey website where they were provided with access to the survey, the guideline recommendations (Section 1) and the evidentiary base (Section 2). The notification email was sent on March 2, 2010. The consultation period ended on April 15, 2010. The working group from the Melanoma DSG reviewed the results of the survey.

Conclusion

This EBS report reflects the integration of feedback obtained through the external review process with final approval given by the Melanoma DSG and the Report Approval Panel of the PEBC.

Recommendations

Major Recommendations

The following recommendations are adopted from the "Clinical practice guidelines for the management of melanoma in Australia and New Zealand."

Excision Margins

After initial excision biopsy, the radial excision margins, measured clinically from the edge of the melanoma, should be:

Melanoma Depth Margin
pTis melanoma in situ 5 mm
pT1 melanoma <1.0 mm 1 cm
pT2 melanoma 1.0 - 2.0 mm 1-2 cm
pT3 melanoma 2.0 - 4.0 mm 1-2 cm
pT4 melanoma >4.0 mm 2 cm

Caution should 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.

Sentinel Lymph Nodes

  • Patients with a melanoma greater than 1.0 mm in thickness should be given the opportunity to discuss sentinel lymph node biopsy (SLNB) to provide staging and prognostic information.
  • SLNB should be performed only, following discussion of the options with the patient, in a unit with access to appropriate surgical, nuclear medicine and pathology services.

Technical Considerations

Excision Margins

  • The depth of the excision should be down to the fascia.
  • Margins (e.g., 1 cm or 2 cm) should be included in the surgical operating room (OR) report.
  • Standard synoptic pathology reporting should be used
  • Excision margins should be 1 to 2 cm where possible but may involve amputation depending on the anatomical location of the lesion (e.g., fingers and toes). For more complex areas such as anus, vulva, vagina, fingers and toes, or where the primary melanoma involves anatomic areas not amenable to simple wide excision, multidisciplinary input should be sought.

Sentinel Lymph Node Biopsy

  • Lymphoscintigraphy is mandatory to identify sentinel lymph nodes.
  • Intradermal injection of radioactive tracer and either patent blue or Lymphazurin blue dye is recommended.
  • SLNB should be discussed with patients with melanomas <1.0 mm in thickness and with high-risk features such as young age, mitotic rate ≥1 mm2, ulceration, and diagnosis by shave biopsy if the deep margin is positive and consequently the depth of the lesion may be underestimated. High-risk features within the clinical context should be considered on an individual basis. In the future, the size of micro-metastases may be used to guide whether or not completion lymph node dissection is performed. However, the data regarding this is still evolving.
  • SLNB should include the use of immunohistochemistry (IHC) and hematoxylin and eosin (H & E) staining.
Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The recommendations are supported by evidence-based guidelines, meta-analyses, and randomized controlled trials.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Sentinel Lymph Node Biopsy

The Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) trial reported no significant difference in melanoma-specific survival between wide excision plus sentinel lymph node biopsy (SLNB) followed by immediate completion lymphadenectomy (CLND) versus wide excision and postoperative observation with CLND at nodal recurrence (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.6-1.25; p=0.58) in patients with melanoma lesions between 1.2 and 3.5 mm thick. Five-year disease-free survival was significantly higher in the SLNB arm than in the control arm (78.3% [versus] vs. 73.1%; HR, 0.74; 95% CI, 0.59 to 0.93; p=0.009). In a planned post-randomization subgroup analysis, patients who underwent immediate lymphadenectomy following positive SLNB had significantly higher five-year survival than did patients who underwent delayed lymphadenectomy for clinically apparent nodal metastases (observation arm). A greater number of metastatic lymph nodes was observed in patients who underwent delayed lymphadenectomy compared to patients who underwent immediate lymphadenectomy following positive SLNB (3.3 vs. 1.4 p<0.001). A multivariate analysis demonstrated that sentinel node status is a significant prognostic factor for disease recurrence and death from melanoma (p<0.001) in the MSLT-1 trial.

Potential Harms

Morbidities associated with sentinel lymph node biopsy include seroma and hematoma (<1 to 5.5%), lymphedema (<1 to 9.2%), wound infection (1 to 4.8%), neurapraxia (≤1.0%), and allergic reactions to blue dye (<1 to 1.2%).

Qualifying Statements

Qualifying Statements
  • Although the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) data regarding sentinel lymph node biopsy (SLNB) is limited to patients with melanomas that are 1.2 to 3.5 mm thick, it was the expert opinion of the working group that the data should be extrapolated to those with melanomas that are ≥1.0-1.2 mm thick and to those with melanomas greater than 3.5 mm thick and clinically node negative. The opinion was that SLNB provides good staging and prognostic information and potentially improved locoregional control.
  • Care has been taken in the preparation of the information contained in this report. Nonetheless, any person seeking to apply or consult the report is expected to use independent medical judgment in the context of individual clinical circumstances or seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representation or guarantees of any kind whatsoever regarding the report content or use or application and disclaims any responsibility for its application or use in any way.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Staying Healthy
IOM Domain
Effectiveness
Safety

Identifying Information and Availability

Bibliographic Source(s)
Wright F, Spithoff K, Easson A, Murray C, Toye J, McCready D, Petrella T, Melanoma Disease Site Group. Primary excision margins and sentinel lymph node biopsy in clinically node-negative cutaneous melanoma of the trunk or extremities: guideline recommendations. Toronto (ON): Cancer Care Ontario (CCO); 2010 May 17. 38 p. (Evidence-based series; no. 8-2).  [56 references]
Adaptation

The recommendations are adopted from the Cancer Council Australia and Australian Cancer Network, Sydney and New Zealand Guidelines Group, "Clinical practice guidelines for the management of melanoma in Australia and New Zealand."

Date Released
2010 May 17
Guideline Developer(s)
Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]
Guideline Developer Comment

The Program in Evidence-based Care (PEBC) is a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Source(s) of Funding

Cancer Care Ontario
Ontario Ministry of Health and Long-Term Care

Guideline Committee

Melanoma Disease Site Group

Composition of Group That Authored the Guideline

For a current list of past and present members, please see the Cancer Care Ontario Web site External Web Site Policy.

Financial Disclosures/Conflicts of Interest

All authors declared no conflicts of interest.

Guideline Status

This is the current release of the guideline.

The EVIDENCE-BASED SERIES report, initially the full original Guideline, over time will expand to contain new information emerging from their reviewing and updating activities.

Please visit the Cancer Care Ontario Web site External Web Site Policy for details on any new evidence that has emerged and implications to the guidelines.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the Cancer Care Ontario Web site External Web Site Policy.

Availability of Companion Documents

The following is available:

  • Browman GP, Levine MN, Mohide EA, Hayward RSA, Pritchard KI, Gafni A, et al. The practice guidelines development cycle: a conceptual tool for practice guidelines development and implementation. J Clin Oncol 1995;13(2):502-12.
Patient Resources

None available

NGC Status

This summary was completed by ECRI Institute on December 10, 2010.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions. Please refer to the Copyright and Disclaimer Statements External Web Site Policy posted at the Program in Evidence-based Care section of the Cancer Care Ontario Web site.

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouseâ„¢ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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