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Guideline Summary
Guideline Title
Merkel cell carcinoma.
Bibliographic Source(s)
Alberta Cutaneous Tumour Team. Merkel cell carcinoma. Edmonton (Alberta): Alberta Health Services, Cancer Care; 2011 Feb. 12 p. (Clinical practice guideline; no. CU-004).  [41 references]
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Merkel cell carcinoma

Guideline Category
Diagnosis
Evaluation
Management
Treatment
Clinical Specialty
Dermatology
Family Practice
Internal Medicine
Oncology
Pathology
Radiation Oncology
Surgery
Intended Users
Advanced Practice Nurses
Physician Assistants
Physicians
Guideline Objective(s)

To provide consensus-based guidelines to improve the diagnosis, treatment, and follow-up for all stages of Merkel cell carcinoma

Target Population

Adults over the age of 18 years with Merkel cell carcinoma

Note: Different principles may apply to pediatric patients.

Interventions and Practices Considered

Diagnosis/Evaluation

  1. Staging (e.g., Memorial Sloan-Kettering Cancer Center Staging System for Merkel cell carcinoma)
  2. History, physical examination, and relevant investigation

Treatment/Management

  1. Surgery
    • Sentinel lymph node biopsy prior to excision
    • Wide local excision
    • Mohs micrographic surgery
    • Pathology report
  2. Adjuvant radiation therapy (primary site and regional lymph node basin)
  3. Chemotherapy
    • Cisplatin or carboplatin
    • Etoposide
    • Topotecan
    • Doxorubicin
  4. Follow-up
    • Physical exam
    • Chest x-ray
    • Monitoring for recurrence
  5. Treatment of recurrent disease
Major Outcomes Considered
  • 2-year, 3-year, and 5-year, and disease-specific survival
  • Recurrence/relapse rate
  • Median time to recurrence
  • Regional lymph node involvement
  • Rate of regional or distant metastasis

Methodology

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

Research Questions

Specific research questions to be addressed by the guideline document were formulated by the guideline lead(s) and Knowledge Management (KM) Specialist using the PICO question format (patient or population, intervention, comparisons, outcomes).

Guideline Questions

  1. What is the widely accepted staging classification for Merkel cell carcinoma (MCC)?
  2. What is the most appropriate treatment for MCC Stage I-IV?
  3. What are the management strategies for recurrence of MCC?
  4. How should a patient with MCC be followed?

Search Strategy

The MEDLINE (1966 through January 2011), CINAHL, Cochrane, American Society of Clinical Oncology (ASCO) Abstracts and proceedings, and CANCERLIT databases were searched. The search included practice guidelines, systematic reviews, meta-analyses, randomized controlled trials, and clinical trials. Search terms included: Merkel cell and cancer or Merkel cell carcinoma.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Not stated
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Evidence was selected and reviewed by a working group comprised of members from the Alberta Cutaneous Tumour Team and a Knowledge Management (KM) Specialist from the Guideline Utilization Resource Unit (GURU). A detailed description of the methodology followed during the guideline development process can be found in the Guideline Utilization Resource Unit Handbook External Web Site Policy (see the "Availability of Companion Documents" field).

Evidence Tables

Evidence tables containing the first author, year of publication, patient group/stage of disease, methodology, and main outcomes of interest are assembled using the studies identified in the literature search. Existing guidelines on the topic are assessed by the KM Specialist using portions of the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument (http://www.agreetrust.org External Web Site Policy) and those meeting the minimum requirements are included in the evidence document. Due to limited resources, GURU does not regularly employ the use of multiple reviewers to rank the level of evidence; rather, the methodology portion of the evidence table contains the pertinent information required for the reader to judge for himself the quality of the studies.

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

Formulating Recommendations

The working group members formulate the guideline recommendations based on the evidence synthesized by the Knowledge Management Specialist during the planning process, blended with expert clinical interpretation of the evidence. As detailed in the Guideline Utilization Resource Unit Handbook External Web Site Policy (see the "Availability of Companion Documents" field), the working group members may decide to adopt the recommendations of another institution without any revisions, adapt the recommendations of another institution or institutions to better reflect local practices, or develop their own set of recommendations by adapting some, but not all, recommendations from different guidelines.

The degree to which a recommendation is based on expert opinion of the working group and/or the Provincial Tumour Team members is explicitly stated in the guideline recommendations. Similar to the American Society of Clinical Oncology (ASCO) methodology for formulating guideline recommendations, the Guideline Utilization Resource Unit does not use formal rating schemes for describing the strength of the recommendations, but rather describes, in conventional and explicit language, the type and quality of the research and existing guidelines that were taken into consideration when formulating the recommendations.

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

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

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

This guideline was reviewed and endorsed by the Alberta Cutaneous Tumour Team.

When the draft guideline document has been completed, revised, and reviewed by the Knowledge Management Specialist and the working group members, it is sent to all members of the Provincial Tumour Team for review and comment. The working group members then make final revisions to the document based on the received feedback, as appropriate. Once the guideline is finalized, it is officially endorsed by the Provincial Tumour Team Lead and the Executive Director of Provincial Tumour Programs.

Recommendations

Major Recommendations

Staging

No widely accepted or standardized staging classification based upon prognosis is available. The Memorial Sloan-Kettering Cancer Center (MSKCC) has developed a four tier staging system based on clinical presentation for patients with Merkel cell carcinoma (MCC). MSKCC's staging system shown in the table below is the most commonly used staging system consistent with the American Joint Committee on Cancer (Allen et al., 2005).

Table. Memorial Sloan-Kettering Cancer Center Staging System for Merkel Cell Carcinoma

  Stage Localized Disease Lymph Node Metastasis
I Primary lesion ≤2 cm + - -
II Primary lesion >2 cm + - -
III Positive lymph node +/- + -
IV Distant metastasis +/- +/- +

History, physical examination, and relevant investigation should guide further treatment.

Treatment

MCC patients with a tumour that is amenable to surgery, and is considered both radiosensitive and chemosensitive, benefit from management in a multidisciplinary manner.

Stage I and II

  • Surgery
    • Sentinel lymph node biopsy (protocol below) should precede excision if possible.
    • Wide local excision (i.e., intra-operative margins of 2 cm if possible, with the final goal being histologically clear pathological margins) has been recommended whenever possible.
    • Mohs micrographic surgery could be considered as a tissue-sparing technique when the tumour is in a sensitive area such as head and neck.
    • Standard elements to be included in the pathology report have been defined by the College of American Pathologists and can be found in the appendix to the original guideline document.
  • Radiation
    • Adjuvant radiation therapy to the primary site should be considered.
    • Adjuvant radiation therapy to the regional lymph node basin is recommended if a sentinel node biopsy cannot be performed.
    • Regimen: 50 Gy to the surgical bed and the draining regional lymphatics, delivered in 2 Gy fractions.
    • For patients with unresected tumours or tumours with microscopic evidence of spread beyond resected margins, higher doses of 56 Gy to 65 Gy have been recommended.
    • As an alternative to adjuvant radiotherapy, observation following surgery could be considered in select patients (i.e., small primary, widely excised, no risk factors).
  • Follow-up
    • Physical exam including complete skin exam and regional lymph node exam
    • Chest x-ray (optional)
    • Frequency:
      • Year 1: every 1 to 3 months
      • Year 2: every 3 to 6 months
      • Years 3+: annual

Stage III

  • Surgery
    • Sentinel lymph node biopsy (protocol below) should precede excision if possible.
    • Wide local excision (i.e., intra-operative margins of 2 cm if possible, with the final goal being histologically clear pathological margins) has been recommended whenever possible.
    • Mohs micrographic surgery could be considered as a tissue-sparing technique when the tumour is in a sensitive area such as head and neck.
    • Completion lymph node dissection or radiation therapy or both should be given to the nodal basin if the sentinel node is positive (Fang et al., 2010).
    • Standard elements to be included in the pathology report have been defined by the College of American Pathologists and can be found in the appendix to the original guideline document.
  • Radiation
    • Adjuvant radiation therapy to the primary site.
    • Adjuvant radiation therapy to the regional lymph node basin if there is macroscopic, clinically positive disease.
    • Regimen: 50 Gy to the surgical bed and the draining regional lymphatics, delivered in 2 Gy fractions.
    • For patients with unresected tumours or tumours with microscopic evidence of spread beyond resected margins, higher doses of 56 Gy to 65 Gy have been recommended.
  • Chemotherapy
    • If sentinel lymph node is positive (i.e., all blue stained nodes and nodes with radioactive counts exceeding 10% of the ex vivo count of the hottest lymph node [Cadili & Dabbs, 2010]), consider adjuvant chemotherapy.
    • Agents:
      • Cisplatin or carboplatin
      • Etoposide
      • Topotecan (in older patients)
  • Follow-up
    • Physical exam including complete skin exam and regional lymph node exam
    • Chest x-ray (optional)
    • Frequency:
      • Year 1: every 1 to 3 months
      • Year 2: every 3 to 6 months
      • Years 3+: annual

Stage IV

  • Chemotherapy
    • Systemic chemotherapy is the treatment most often used for patients with stage IV disease.
    • Because of morphologic and immunohistochemical similarities, the regimens employed are similar to those used for patients with small cell lung cancer:
      • Cisplatin or carboplatin
      • Etoposide
      • Topotecan (in older patients)
      • Doxorubicin
  • Surgery: as indicated
  • Radiation: as indicated
  • Follow-up
    • Physical exam including complete skin exam and regional lymph node exam
    • Chest x-ray (optional)
    • Frequency:
      • Year 1: every 1 to 3 months
      • Year 2: every 3 to 6 months
      • Years 3+: annual

Recurrence

  • Local or regional recurrences: Individualize treatment.
  • Disseminated recurrence: Treat as Stage IV disease.

Sentinel Lymph Node Biopsy Protocol

Lymph node deposits of metastatic MCC may be difficult to identify on routine hematoxylin and eosin (H&E)-stained sections. As for melanoma and breast carcinoma, the use of immunohistochemistry has been shown to increase the sensitivity of identifying occult lymph node metastases (Allen et al., 2001).

Based on recommendations from the College of American Pathologists (Rao et al., 2010) and discussions with M.D. Anderson Cancer Center (Prieto, personal communication, 2010), the following protocol is suggested:

  • Bisect sentinel lymph node.
  • If initial H&E section is negative, then cut 200 μm into block and repeat H&E stain.
  • Perform anti-keratin immunohistochemistry, preferably using an antibody cocktail, including antibody against low-molecular weight keratin (e.g., Cam 5.2).
  • If any concerns regarding non-epithelial keratin staining, anti-cytokeratin 20 immunohistochemistry can be performed.

As for melanoma, the number, size, and intra-nodal location of any metastatic deposits of MCC should be documented in the final pathology report (see the appendix to the original guideline document).

Prognosis and Follow-up Evaluation

  • Patients should be monitored closely for recurrence of locoregional or distant disease. Lymph node or distant metastatic disease has a uniformly grave prognosis; however, there may be a role for chemotherapy in prolonging survival.
  • Given the complex issues in dealing with this aggressive tumour, patients are best served by being cared for in a tertiary care setting with a multidisciplinary approach.
Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

References Supporting the Recommendations
Type of Evidence Supporting the Recommendations

The recommendations are supported in part by systematic reviews and/or new or updated practice guidelines.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate management of Merkel cell carcinoma

Potential Harms

Not stated

Qualifying Statements

Qualifying Statements

The recommendations contained in this guideline are a consensus of the Alberta Cutaneous Tumour Team and are a synthesis of currently accepted approaches to management, derived from a review of relevant scientific literature. Clinicians applying these guidelines should, in consultation with the patient, use independent medical judgment in the context of individual clinical circumstances to direct care.

Implementation of the Guideline

Description of Implementation Strategy
  • Present the guideline at the local and provincial tumour team meetings and weekly rounds.
  • Post the guideline on the Alberta Health Services Web site.
  • Send an electronic notification of the new guideline to all members of Alberta Health Services, Cancer Care.
Implementation Tools
Chart Documentation/Checklists/Forms
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Living with Illness
IOM Domain
Effectiveness

Identifying Information and Availability

Bibliographic Source(s)
Alberta Cutaneous Tumour Team. Merkel cell carcinoma. Edmonton (Alberta): Alberta Health Services, Cancer Care; 2011 Feb. 12 p. (Clinical practice guideline; no. CU-004).  [41 references]
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2011 Feb
Guideline Developer(s)
CancerControl Alberta - State/Local Government Agency [Non-U.S.]
Source(s) of Funding

Alberta Health Services, Cancer Care

Guideline Committee

Alberta Cutaneous Tumour Team

Composition of Group That Authored the Guideline

Not stated

Financial Disclosures/Conflicts of Interest

Participation of members of the Alberta Provincial Cutaneous Tumour Team in the development of this guideline has been voluntary and the authors have not been remunerated for their contributions. There was no direct industry involvement in the development or dissemination of this guideline. Alberta Health Services, Cancer Care recognizes that although industry support of research, education and other areas is necessary in order to advance patient care, such support may lead to potential conflicts of interest. Some members of the Alberta Provincial Cutaneous Tumour Team are involved in research funded by industry or have other such potential conflicts of interest. However the developers of this guideline are satisfied it was developed in an unbiased manner.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the Alberta Health Services Web site External Web Site Policy.

Availability of Companion Documents

The following is available:

  • Guideline utilization resource unit handbook. Edmonton (Alberta): Alberta Health Services, Cancer Care; 2011 Dec. 5 p. Electronic copies: Available in Portable Document Format (PDF) from the Alberta Health Services Web site External Web Site Policy.

In addition, the College of American Pathologists' checklist for reporting elements for Merkel cell carcinoma following incisional biopsy, excision, re-excision, or lymphadenectomy is available in the appendix to the original guideline document External Web Site Policy.

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on December 24, 2012. The information was verified by the guideline developer on February 13, 2013.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

Disclaimer

NGC Disclaimer

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

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