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
- 1Clinical trials have demonstrated the clinical efficacy of the human papillomavirus vaccine in reducing the burden of vulvar intraepithelial neoplasia and, potentially, vulvar cancer (high).
- 2Early 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).
- 3The morbidity of inguinofemoral lymph node dissection for vulvar cancer can be significant and sentinel lymph node biopsy can reduce these complications (high).
- 4There is a detection rate for inguinofemoral sentinel lymph nodes of 87% per groin when using a combination of radioactive colloid and blue dye (moderate).
- 5Lateralized 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).
- 6Adjuvant radiation treatment improves overall survival when given for inguinofemoral macrometastases (high) and close surgical margins for squamous cell cancer of the vulva (low).
- 7The addition of chemotherapy as a radiation sensitizer to radiation treatments may improve overall outcomes (low).
- 8Primary radiotherapy can be used when surgery is either not an option or would cause extreme morbidity (moderate).
- 9There 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).
- 10Squamous cell cancers of the vulva have a high recurrence rate due to their association with human papillomavirus and skin dysplasia (high).
- 11Vulvar 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
- 1Any 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).
- 2Once vulvar squamous cell cancer is diagnosed, a referral should be made to a gynaecologic oncologist (strong, high).
- 3Clinicians 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).
- 4Inguinal 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).
- 5Surgeons 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).
- 6Adjuvant 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).
- 7We 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).
- 8The addition of radiosensitizing chemotherapy to adjuvant radiation may be beneficial; however, the evidence is extrapolation from cervical and anal canal cancer protocols (weak, low).
- 9Chemotherapy should be considered as a radiosensitizer in primary radiation treatment (weak, low).
- 10Primary 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).
- 11Patients 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).
- 12There 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).
- 13There 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).
- 14All 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)To read this article in full you will need to make a payment
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References
National Cancer Institute. Cancer Stat Facts: Vulvar Cancer. Bethesda, MD: National Cancer Institute. Available at: https://seer.cancer.gov/statfacts/html/vulva.html. Accessed on August 3, 2018.
- Canadian Cancer Statistics 2015.Canadian Cancer Society, Toronto2015 (Available at:) (Accessed on August 3, 2018)
- Cancer of the cervix, vagina and vulva.in: DeVita VT Jr Lawrence TS Rosenberg SA Cancer: principles & practice of oncology. 9th ed. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia2011: 1311-1344
- Cancer of the vulva: an analysis of 155 cases.Am J Obstet Gynecol. 1960; 79: 692-699
- New gynecologic cancer staging.Obstet Gynecol. 1990; 75: 287-288
- Cervical and vulva cancer: changes in FIGO definitions of staging.Br J Obstet Gynaecol. 1996; 103: 405-406
- Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium.Int J Gynaecol Obstet. 2009; 105: 103-104
- Validation of the 2009 FIGO staging system for for carcinoma of the vulva.Int J Gynecol Cancer. 2012; 22: 498-502
- Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival. (Gynecologic Oncology Group Study).Am J Obstet Gynecol. 1991; 164: 997-1003
- Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.J Low Genit Tract Dis. 2012; 16: 471-479
- Fall in human papillomavirus prevalence following a national vaccination program.J Infect Dis. 2012; 206: 1645-1651
- Improving diagnostic yield of punch biopsies of the skin.Indian J Dermatol Venereol Leprol. 2008; 74: 527-531
- Committee opinion no. 675: management of vulvar intraepithelial neoplasia.Obstet Gynecol. 2016; 128: e178-e182
- Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.N Engl J Med. 2007; 356: 1928-1943
- Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions.N Engl J Med. 2007; 356: 1915-1927
- Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial.Lancet. 2007; 369: 2161-2170
- Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica.Vaccine. 2008; 26: 4795-4808
- Contemporary clinical questions on HPV-related diseases and vaccination.2nd ed. Society of Gynecologic Oncology of Canada, Ottawa2015 (abridged versionAvailable at:) (Accessed on August 3, 2018)
- Radical resection of vulvar malignancies: a paradigm shift in surgical approaches.Curr Opin Obstet Gynecol. 1999; 11: 61-64
- Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early stage vulvar cancer: results from GROINSS-V, a multicentre observational study.Lancet Oncol. 2010; 11: 646-652
- Repeat sentinel lymph node procedure in patients with recurrent vulvar squamous cell carcinoma is feasible.Gynecol Oncol. 2016; 140: 415-419
- Secondary sentinel node biopsy after previous excision of the primary tumor in squamous cell carcinoma of the vulva.Ann Surg Oncol. 2013; 20: 1701-1706
- Is bilateral lymphadenectomy for midline squamous carcinoma of the vulva always necessary? An analysis from Gynecologic Oncology Group (GOG) 173.Gynecol Oncol. 2013; 128: 155-159
- The risk of contralateral non-sentinel metastasis in patients with primary vulvar cancer and unilaterally positive sentinel node.Ann Surg Oncol. 2016; 23: 2508-2514
- Sentinel lymph node biopsy in vulvar cancer: systematic review, meta-analysis and guideline recommendations.Gynecol Oncol. 2015; 137: 351-361
- Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: a Gynecologic Oncology Group study.J Clin Oncol. 2012; 30: 3786-3791
- Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer.Am J Clin Oncol. 1987; 10: 171-181
- Pelvic exenteration in the age of modern chemoradiation.Gynecol Oncol. 2011; 121: 131-134
- Effective chemotherapy consisting of bleomycin, vincristine, mitomycin C. and cisplatin (BOMP) for a patient with inoperable vulvar cancer.Gynecol Oncol. 1990; 36: 423-427
- Cisplatin (P), bleomycin (B) and methotrexate (M) preoperative chemotherapy in locally advanced vulvar carcinoma.Gynecol Oncol. 1993; 50: 49-53
- Bleomycin, methotrexate and CCNU in advanced inoperable squamous cell carcinoma of the vulva: a phase II study of the EORTC Gynaecological Cancer Cooperative Group (GCCG).Gynecol Oncol. 1990; 37: 359-362
- Neoadjuvant chemoradiation for advanced primary vulvar cancer.Cochrane Database Syst Rev. 2006; CD003752
- Preoperative chemo-radiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.Int J Radiat Oncol Biol Phys. 1998; 42: 79-85
- Primary versus preoperative radiation for locally advanced vulvar cancer.Int J Gynecol Cancer. 2017; 27: 794-804
- Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes.Obstet Gynecol. 1986; 68: 733-740
- Radiation therapy compared with pelvic node resection of node positive vulvar cancer: a randomized controlled trial.Obstet Gynecol. 2009; 114: 537-546
- Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study.Int J Radiat Oncol Biol Phys. 1992; 24: 389-396
- Femoral vessel depth and the implications for groin node radiation.Int J Radiat Oncol Biol Phys. 1993; 27: 969-974
- Inguinofemoral radiation of N0,N1 vulvar cancer may be equivalent to lymphadenectomy if proper radiation technique is used.Int J Radiat Oncol Biol Phys. 1993; 27: 963-967
- The role of radiation therapy in vulvar cancer: review of the current literature.Tumori. 2017; 103: 422-429
- Intensity-modulated radiotherapy for the treatment of vulvar carcinoma: a comparative dosimetric study with early clinical outcome.Int J Radiat Oncol Biol Phys. 2006; 64: 1395-1400
- Preoperative intensity-modulated radiotherapy and chemotherapy for locally advanced vulvar carcinoma.Gynecol Oncol. 2008; 109: 291-295
- Genital invasion or perigenital spread may pose a risk of marginal misses for intensity modulated radiotherapy (IMRT) in anal cancer.Radiat Oncol. 2016; 11: 53
- Vulvar recurrences after intensity-modulated radiation therapy for squamous cell carcinoma of the anus.Am J Clin Oncol. 2018; 41: 492-496
- Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva.Gynecol Oncol. 1990; 38: 309-314
- Tumour-free margins in vulvar squamous cell carcinoma: does distance really matter?.Eur J Cancer. 2016; 65: 139-149
- Role of tumour-free margin distance for loco-regional control in vulvar cancer: a subset analysis of the Arbeitsgemeinschaft Gynakologische Onkologie CaRE-1 multicenter study.Eur J Cancer. 2016; 69: 180-188
- Adjuvant radiotherapy for vulvar cancer with close or positive surgical margins.J Cancer Res Clin Oncol. 2016; 142: 489-495
- The role of chemo-radiotherapy in the management of locally advanced carcinoma of the vulva: single institutional experience and review of literature.Am J Clin Oncol. 2011; 34: 22-26
- Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: a National Cancer Database (NCDB) analysis.Gynecol Oncol. 2015; 137: 365-372
- Surgical management vs primary radiotherapy for vulvar cancer [abstract].Gynecol Oncol. 2017; 145: 216
- Comparison of outcome measures in patients with advanced squamous cell carcinoma of the vulva treated with surgery or primary chemoradiation.Gynecol Oncol. 2008; 108: 584-590
- Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.Int J Radiat Oncol Biol Phys. 1998; 42: 79-85
- Treatment outcomes of curative radiotherapy in patients with vulvar cancer: results of the retrospective KROG 1203 study.Radiat Oncol J. 2015; 33: 198-206
- Principles and practice of gynecologic oncology.6th ed. Lippincott Williams & Wilkins, Philadelphia2013
- Berek and Hacker's gynecologic oncology.6 ed. Lippincott Williams & Wilkins, Philadelphia2014
- Neoadjuvant chemotherapy in advanced vulvar cancer.Int J Gynecol Cancer. 2010; 20: 294-298
- Role of paclitaxel and cisplatin as the neoadjuvant treatment for locally advanced squamous cell carcinoma of the vulva.J Gynecol Oncol. 2014; 25: 22-29
- Neoadjuvant chemotherapy in vulvar cancer: avoiding primary exenteration.Gynecol Oncol. 2006; 100: 53-57
- Tailoring the treatment of locally advanced squamous cell carcinoma of the vulva: neoadjuvant chemotherapy followed by radical surgery: results from a multicenter study.Int J Gynecol Cancer. 2012; 22: 1258—63
- Weekly paclitaxel/carboplatin in the treatment of locally advanced, recurrent, or metastatic vulvar cancer.Int J Gynecol Cancer. 2012; 22: 865-868
- Phase II study on paclitaxel in patients with recurrent, metastatic or locally advanced vulvar cancer not amenable to surgery or radiotherapy: a study of the EORTC-GCG (European Organisation for Research and Treatment of Cancer–Gynaecological Cancer Group).Ann Oncol. 2009; 20: 1511-1516
- Neoadjuvant and definitive chemotherapy or chemoradiation for stage III and IV vulvar cancer: a pooled reanalysis.Eur J Obstet Gynecol Reprod Biol. 2017; 212: 115-118
- A case of recurrent squamous cell carcinoma of the vulva successfully treated by combination therapy with cetuximab and paclitaxel.Br J Dermatol. 2016; 174: 677-678
- Recurrent metastatic vulvar carcinoma treated with cisplatin plus cetuximab.Int J Gynecol Cancer. 2008; 18: 1132-1135
- Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva.Gynecol Oncol. 2012; 127: 141-146
- Patterns of recurrence in patients with squamous cell carcinoma of the vulva: a multicentre CTF study.Cancer. 2000; 89: 116-122
- The value of routine follow-up in patients treated for carcinoma of the vulva.Cancer. 2003; 98: 2624-2629
- Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.Crit Rev Oncol Hematol. 2012; 83: 71-83
- Local and regional recurrence of vulval cancer: management dilemmas.Best Pract Res Clin Obstet Gynaecol. 2003; 17: 663-681
- Risk factors and treatment for recurrent vulvar squamous cell carcinoma.Crit Rev Oncol Hematol. 2016; 106: 1-13
- Long-term survival and disease recurrence in patients with primary squamous cell carcinoma of the vulva.Gynecol. Oncol. 2005; 97 (828–3)
- Prognostic importance of human papillomavirus (HPV) and p16 positivity in squamous cell carcinoma treated with radiotherapy.Gynecol Oncol. 2016; 142: 293-298
- Carcinoma of the vulva. FIGO 26th annual report on the results of treatment in gynecological cancer.Int J Gynaecol Obstet. 2006; 95: S7-27
- Should groin recurrence still be considered as a palliative situation in vulvar cancer patients? A brief report.Int J Gynecol Cancer. 2016; 26: 575-579
- Groin recurrence in carcinoma of the vulva: management and outcome.Eur J Cancer Care (Engl). 2010; 19: 302-307
Article info
Publication history
No. 370, January 2019 (Replaces No. 180, July 2006)
Footnotes
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written permission of the publisher.
All people have the right and responsibility to make informed decisions about their care in partnership with their health care providers. In order to facilitate informed choice, patients should be provided with information and support that is evidence-based, culturally appropriate and tailored to their needs.
This guideline was written using language that places women at the centre of care. That said, the SOGC is committed to respecting the rights of all people - including transgender, gender non-binary, and intersex people - for whom the guideline may apply. We encourage healthcare providers to engage in respectful conversation with patients regarding their gender identity as a critical part of providing safe and appropriate care. The values, beliefs and individual needs of each patient and their family should be sought and the final decision about the care and treatment options chosen by the patient should be respected.
Identification
Copyright
© 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.
