title: Systemic therapy in squamous cell carcinoma of the vulva: current status and future directions.
abstract: OBJECTIVE
  The advances achieved in the surgical management of vulvar squamous cell carcinoma (SCC) have not been mirrored in systemic therapy options. The objective of this paper is to summarize current evidence regarding systemic therapy in vulvar cancer, review the latest research on the biology of this disease, and identify future strategies to improve patient management.
  
  
  METHODS
  MEDLINE and EMBASE were searched for all relevant English-language articles from inception to December 10, 2012. Existing evidence regarding systemic therapy in vulvar SCC was synthesized descriptively, with an emphasis on prospective studies when available. Single-patient case-reports were excluded.
  
  
  RESULTS
  We identified 12 studies of neoadjuvant chemoradiation, 8 studies of neoadjuvant chemotherapy alone, 18 studies of chemoradiation as primary therapy, 4 studies of chemotherapy in the adjuvant setting, and 8 studies of chemotherapy for recurrent or metastatic disease. Review of the biology of vulvar cancer was performed, and promising targets for the future were identified based on the two biologic pathways of disease development. New therapeutic strategies such as immune-therapy and targeted agents hold promise for the future.
  
  
  CONCLUSIONS
  Advances in systemic therapy for vulvar SCC are urgently needed, especially in the setting of recurrent and metastatic disease. A focus on the investigation of new targeted agents is encouraged and consideration of quality of life and sexual health issues is essential. International cooperation and adaptive trial designs are required to improve outcomes for this group of traditionally under-served women.
authors.affiliation: Division of Gynecologic Oncology, University of Toronto, M700-610 University Avenue, Toronto, ON M5N 2L5, Canada. Electronic address: clare.reade@mail.utoronto.ca.
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Reade
authors.affiliation: Division of Gynecologic Oncology, University of Toronto, M700-610 University Avenue, Toronto, ON M5N 2L5, Canada; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Juravinski Cancer Centre, McMaster University, 699 Concession St, Hamilton, ON L8V 5C2, Canada. Electronic address: lua.eiriksson@jcc.hhsc.ca.
authors.forename: Lua R
authors.initials: LR
authors.lastname: Eiriksson
authors.affiliation: Division of Medical Oncology and Hematology, University of Toronto, Canada; Princess Margaret Hospital, 610 University Avenue, Toronto, ON M5G 2M9, Canada. Electronic address: helen.mackay@uhn.ca.
authors.forename: Helen
authors.initials: H
authors.lastname: Mackay
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D014846:Vulvar Neoplasms / Q000628:therapy*
keywords: Chemoradiation; Chemotherapy; Systemic therapy; Targeted agents; Vulvar cancer