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No. 370-Management of Squamous Cell Cancer of the Vulva

      Abstract

      Objective

      This guideline reviews the clinical evaluation and management of squamous cell cancer (SCC) of the vulva with respect to diagnosis, primary surgical, radiation, or chemotherapy management and need for adjuvant treatment with chemotherapy and/or radiation therapy. Other vulvar cancer pathologic diagnoses are not included in the guideline.

      Intended Users

      The first part of this document which includes recommendations 1 through 3 is for general gynaecologists, obstetricians, family doctors, registered nurses, nurse practitioners, residents, and health care providers with a focus on the presentation, diagnosis, and updated information about surgical procedures performed by subspecialists. The surgical management and treatment of advanced vulvar cancer are intended for gynaecologic oncologists, radiation oncologists, and medical oncologists who treat these complex patients. This guideline is intended to provide information for interested parties who may follow these patients once treatment is complete.

      Target Population

      Adult women (18 years and older) with SCC of the vulva. Excluded from these guidelines are women with preinvasive disease.

      Options

      Women diagnosed with SCC of the vulva should be referred to a gynaecologic oncologist for initial evaluation, consideration for primary surgery and inguinal lymph node assessment, and potentially adjuvant radiation and/or chemotherapy. All cases of vulvar cancer should have access to discussion at a multidisciplinary cancer case conference. Women who would otherwise require radical surgery such as abdominal-perineal resection or exenterative procedures may be considered for primary treatment with radiation and/or chemotherapy.

      Evidence

      For this guideline, relevant studies were searched in PubMed, Medline, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials: vulva, vulvar cancer, inguinofemoral lymph node dissection, sentinel nodes, systemic chemotherapy, radiotherapy, neoadjuvant, adjuvant, primary, exenteration, survival, follow up. The initial search was performed in September 2016 with a final literature search in May 2017. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 286, and 78 studies were included in this review.

      Validation Methods

      The content and recommendations were drafted and agreed upon by the principal authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework (Table 1). The interpretation of strong and weak recommendations is described in Table 2. The Summary of Findings is available upon request.

      Benefits, harms, and/or costs

      These guidelines are to encourage physicians in the appropriate use of sentinel inguinal lymph node assessment for SCC of the vulva. The committee also promotes the centralization of treatment of vulvar cancer in specialized treatment centres.

      Guideline update

      Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.

      Sponsors

      This guideline was developed with resources funded by the Society of Gynecologic Oncology of Canada and the Society of Obstetricians and Gynaecologists of Canada.

      Summary Statements

      • 1
        Clinical trials have demonstrated the clinical efficacy of the human papillomavirus vaccine in reducing the burden of vulvar intraepithelial neoplasia and, potentially, vulvar cancer (high).
      • 2
        Early stage vulvar cancer is well managed with local surgical excision and assessment of inguinal lymph node status for those with International Federation of Gynecology and Obstetrics stage IB and resectable stage II tumours (high).
      • 3
        The morbidity of inguinofemoral lymph node dissection for vulvar cancer can be significant and sentinel lymph node biopsy can reduce these complications (high).
      • 4
        There is a detection rate for inguinofemoral sentinel lymph nodes of 87% per groin when using a combination of radioactive colloid and blue dye (moderate).
      • 5
        Lateralized squamous cell cancer of the mid to posterior vulva (>1 cm from the midline) can forgo bilateral surgical assessment of clinically normal inguinofemoral lymph nodes (high).
      • 6
        Adjuvant radiation treatment improves overall survival when given for inguinofemoral macrometastases (high) and close surgical margins for squamous cell cancer of the vulva (low).
      • 7
        The addition of chemotherapy as a radiation sensitizer to radiation treatments may improve overall outcomes (low).
      • 8
        Primary radiotherapy can be used when surgery is either not an option or would cause extreme morbidity (moderate).
      • 9
        There is a paucity of data for the systemic treatment of surgically unresectable squamous cell cancer of the vulva, advanced disease with distant metastases, or recurrent disease previously treated with surgery, and/or radiation with or without chemotherapy, but platinum-based therapies currently demonstrate the greatest activity available (low).
      • 10
        Squamous cell cancers of the vulva have a high recurrence rate due to their association with human papillomavirus and skin dysplasia (high).
      • 11
        Vulvar squamous cell cancer with nodal recurrence is typically fatal and its treatment should be individualized and guided by the size of disease and previous treatment (low).

      Recommendations

      • 1
        Any worrisome vulvar lesion should be referred to an appropriate clinician for vulvar biopsy. Punch biopsies of adequate size (at least 4 mm wide) and depth (to subcutaneous fat) are most likely to achieve pathologic diagnosis (strong, high).
      • 2
        Once vulvar squamous cell cancer is diagnosed, a referral should be made to a gynaecologic oncologist (strong, high).
      • 3
        Clinicians should strongly recommend the human papillomavirus vaccine for all females 9 to 45 years of age to reduce the burden of all human papillomavirus–related diseases (strong, high).
      • 4
        Inguinal sentinel lymph node mapping for surgical staging of vulvar cancer is appropriate for unifocal tumours, <4 cm in widest diameter, of squamous cell histology, and where lymph nodes are not clinically suspicious (strong, high).
      • 5
        Surgeons developing skills in sentinel lymph node mapping for vulvar cancer staging should perform a minimum of 10 correlated cases of sentinel lymph node biopsy with subsequent complete inguinofemoral lymph node dissection prior to sentinel node mapping alone to reduce false-negative rates (strong, high).
      • 6
        Adjuvant radiation, including both inguinal and pelvic fields, should be given for any inguinofemoral lymph node macrometastasis (≥5 mm), 2 or more micrometastases (<5 mm), or extracapsular spread (strong, high).
      • 7
        We suggest that adjuvant radiotherapy should be given for close (≤10 mm on fresh and ≤8 mm on fixed pathologic specimens) and positive surgical margins for squamous cell cancer of the vulva if surgical re-excision is not feasible or has potential for high surgical morbidity (weak, low).
      • 8
        The addition of radiosensitizing chemotherapy to adjuvant radiation may be beneficial; however, the evidence is extrapolation from cervical and anal canal cancer protocols (weak, low).
      • 9
        Chemotherapy should be considered as a radiosensitizer in primary radiation treatment (weak, low).
      • 10
        Primary radiotherapy should be given to patients who are not candidates for radical surgery, or where surgery would compromise the function of an organ (i.e., urethra, anus) (strong, moderate).
      • 11
        Patients with extensive vulvar squamous cell cancer that would require primary exenterative procedures for surgical removal should be assessed in a multidisciplinary setting with surgical and radiation teams for consideration of primary chemoradiation. When surgery is the preferred primary treatment for locally advanced squamous cell cancer of the vulva, a comprehensive approach is recommended for optimal results, including specialized surgical teams, which may include gynaecologic oncology, general surgery, plastic surgery, and urology (strong, high).
      • 12
        There is currently insufficient evidence to offer recommendations for a specific systemic chemotherapy combination, duration, or method of delivery for the treatment of squamous cell cancer of the vulva (weak, low).
      • 13
        There is a need for large cooperative group trials to determine the best treatment for women requiring systemic chemotherapy for squamous cell cancer of the vulva (strong, high).
      • 14
        All women previously treated for vulvar cancer benefit from long-term follow-up provided by an experienced health care provider able to detect any recurrence or second gynaecologic malignancy (weak, low).

      Key Words

      Abbreviations:

      FIGO (International Federation of Gynecology and Obstetrics), GROINNSS-V (GROningen INternational Study on Sentinel nodes in Vulvar cancer), HPV (human papillomavirus), IFLD (inguinofemoral lymph node dissection), OS (overall survival), SCC (squamous cell cancer), SLNB (sentinel lymph node biopsy)
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