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Prognostic factors in patients with vulvar cancer: the VULCAN study
  1. Ignacio Zapardiel1,
  2. Sara Iacoponi1,
  3. Pluvio J Coronado2,
  4. Kamil Zalewski3,
  5. Frank Chen4,
  6. Christina Fotopoulou4,
  7. Polat Dursun5,
  8. Ioannis C Kotsopoulos6,
  9. Robert Jach7,
  10. Alessandro Buda8,
  11. Maria J Martinez-Serrano9,
  12. Christoph Grimm10,
  13. Robert Fruscio8,
  14. Enrique Garcia11,
  15. Jacek Jan Sznurkowski12,
  16. Cristina Ruiz13,
  17. Maria C Noya14,
  18. Dib Barazi15,
  19. Javier Diez16,
  20. Begoña Diaz De la Noval17,
  21. Arnoldas Bartusevicius18,
  22. Pierandrea De Iaco19,
  23. Maria Otero20,
  24. Maria Diaz21,
  25. Dimitrios Haidopoulos22,
  26. Silvia Franco23,
  27. Pawel Blecharz24,
  28. Miguel A Zuñiga25,
  29. Patricia Rubio26,
  30. Barbara Gardella27,
  31. Dimitrios C Papatheodorou28,
  32. Yusuf Yildirim29,
  33. Francesc Fargas30 and
  34. Ronalds Macuks31
  35. VULCAN Study coinvestigators
    1. 1Gynecologic Oncology Unit, La Paz University Hospital - IdiPAZ, Madrid, Spain
    2. 2Gynecology Department, Hospital Clinico Universitario San Carlos - IdISSC, Madrid, Spain
    3. 3Gynecologic Oncology Department, Maria Sklodowska-Curie Memorial Cancer Center – Institute of Oncology, Warsaw, Poland
    4. 4Department of Gynecology, Campus Virchow-Klinikum, Charite Universitatsmedizin Berlin, Berlin, Germany
    5. 5Department of Obstetrics and Gynecology Division of Gynecologic Oncology, Baskent University School of Medicine, Ankara, Turkey
    6. 6Gynecological Oncology Department, Theagenio Cancer Hospital, Thessaloniki, Greece
    7. 7Gynecology Department, University Hospital, Jagiellonian University, Krakow, Poland
    8. 8Gynecologic Oncology Department, Hospital San Gerardo, Monza, Lombardia, Italy
    9. 9Gynecologic Oncology Unit, Vall d'Hebron Institut d'Oncologia, Barcelona, Spain
    10. 10Division of General Gynaecology and Gynaecological Oncology, Medical University of Vienna - Vienna General Hospital, Vienna, Austria
    11. 11Gynecologic Oncology Department, Fundacion Instituto Valenciano de Oncologia, Valencia, Spain
    12. 12Department of Surgical Oncology, Medical University of Gdańsk, Gdańsk, Poland
    13. 13Gynecologic Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain
    14. 14Gynecology Department, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, Spain
    15. 15Gynecologic Oncology Department, Ciudad Sanitaria de Bellvitge, Barcelona, Spain
    16. 16Gynecologic Oncology Department, Hospital de Cruces, Vizcaya, Spain
    17. 17Gynecology Department, Hospital Universitario Central de Asturias, Spain
    18. 18Gynecologic Oncology Department, Hospital of Lithuanian University of Health Sciences Kauno Klinikos, Kaunas, Lithuania
    19. 19Gynecology Department, Policlinico S. Orsola-Malpighi, Bologna, Italy
    20. 20Gynecology Department, Complejo Hospitalario de Leon, Leon, Spain
    21. 21Gynecology Department, Complejo Hospitalario Universitario Juan Canalejo, La Coruña, Spain
    22. 22Gynecologic Oncology, Alexandra Hospital, Athens, Greece
    23. 23Gynecology Department, Hospital Vall D’Hebron, Barcelona, Spain
    24. 24Gynecologic Oncology Department, Maria Sklodowska-Curie Memorial Cancer Center, Krakow, Poland
    25. 25Gynecology Department, Complejo Hospitalario Torrecardenas, Almeria, Spain
    26. 26Gynecology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain
    27. 27Gynecologic Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
    28. 28Gynecology Department, Metaxa Memorial Cancer Hospital, Athens, Greece
    29. 29Gynecologic Oncology Department, Ege Gynaecology Training and Research Hospital, Izmir, Turkey
    30. 30Gynecology Department, Instituto Universitario Dexeus, Barcelona, Spain
    31. 31Gynecologic Oncology Department, Riga East Clinical University Hospital Latvian Oncology Center, Riga, Latvia
    1. Correspondence to Professor Pluvio J Coronado, Hospital Clinico Universitario San Carlos, Madrid, Madrid, Spain; pcoronadom{at}


    Objective This study aimed to analyze the prognostic factors for overall and progression-free survival in patients with vulvar cancer.

    Methods This international, multicenter, retrospective study included 2453 patients diagnosed with vulvar cancer at 100 different institutions. Inclusion criteria were institutional review board approval from each collaborating center, pathologic diagnosis of invasive carcinoma of the vulva, and primary treatment performed at the participating center. Patients with intraepithelial neoplasia or primary treatment at non-participating centers were excluded. Global survival analysis and squamous cell histology subanalysis was performed.

    Results After excluding patients due to incomplete data entry, 1727 patients treated for vulvar cancer between January 2001 and December 2005 were registered for analysis (1535 squamous, 42 melanomas, 38 Paget’s disease and 112 other histologic types). Melanomas had the worse prognosis (p=0.02). In squamous vulvar tumors, independent factors for increase in local recurrence of vulvar cancer were: no prior radiotherapy (p<0.001) or chemotherapy (p=0.006), and for distant recurrence were the number of positive inguinal nodes (p=0.025), and not having undergone lymphadenectomy (p=0.03) or radiotherapy (p<0.001), with a HR of 1.1 (95% CI 1.2 to 1.21), 2.9 (95% CI 1.4 to 6.1), and 3.1 (95% CI 1.7 to 5.7), respectively. Number of positive nodes (p=0.008), FIGO stage (p<0.001), adjuvant chemotherapy (p=0.001), tumor resection margins (p=0.045), and stromal invasion >5 mm (p=0.001) were correlated with poor overall survival, and large case volume (≥9 vs <9 cases per year) correlated with more favorable overall survival (p=0.05).

    Conclusions Advanced patient age, number of positive inguinal lymph nodes, and lack of adjuvant treatment are significantly associated with a higher risk of relapse in patients with squamous cell vulvar cancer. Case volume per treating institution, FIGO stage, and stromal invasion appear to impact overall survival significantly. Future prospective trials are warranted to establish these prognostic factors for vulvar cancer.

    • vulvar and vaginal cancer
    • vulvar neoplasms
    • neoplasm recurrence, local

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    • Collaborators Arones M (Complejo Hospitalario Universitario de Albacete, Spain), Arque M (Hospital de Santa Creu i Sant Pau, Spain), Barbara Gardella B (Fondazione IRCCS Policlinico San Matteo, Pavia, Italy), Bartusevicius A (Lithuanian University of Health Sciences, Kaunas, Lithuania), Bernal MT (Hospital de Donostia, San Sebastian, Spain), Blecharz P (Maria Sklodowska-Curie Memorial Cancer Center, Krakow, Poland), Ceccaroni M (Sacred Heart Hospital Negrar, Verona, Italy), Covo-Pinto L (Hospital Universitario Marques de Valdecilla, Santander, Spain), Cristobal I (Hospital Sanitas La Zarzuela, Madrid, Spain), Cruz JL (Hospital de la Ribera, Spain), De la Torre J (Hospital Universitario de Canarias, Spain), De Iaco P (Policlinico S. Orsola-Malpighi, Bologna, Italy), Diaz M (Complejo Hospitalario Universitario Juan Canalejo, La Coruña, Spain), Diaz-De la Noval B (Hospital Universitario Central de Asturias, Spain), DiFiore H (Fundacion Jimenez Diaz, Madrid, Spain), Dogan A (Ege Gynaecology Training and Research Hospital, Turkey), Etxabe I (Instituto Oncologico de Gipuzkoa, Spain), Fargas F (Instituto Universitario Dexeus, Barcelona, Spain), Franco S (Hospital Vall D'Hebron, Barcelona, Spain), Feijoo L (Hospital Virgen de la Concha, Zamora, Spain), Fernandez A (Hospital Costa del Sol, Marbella, Spain), Fernandez L (Hospital de Cabueñes, Gijon, Spain), Fernandez M (Complejo Hospitalario de Pontevedra, Spain), Festi A (Policlinico G.B. Rossi, Verona, Italy), Garcia-Casals C, (Complejo Hospitalario Juan Canalejo, La Coruña, Spain), Garrido RA (Complejo Hospitalario de Ciudad Real, Spain), Gil-Ibañez B (Corporacion Sanitaria Parc Tauli, Spain), Gil-Moreno A (Hospital Vall D'Hebron, Barcelona, Spain), Gines A (Hospital Universitario Puerto Real, Spain), Gomez AI (Complejo Asistencial de Segovia, Spain), Gomez I (Hospital Virgen del Camino, Pamplona, Spain), Gonçalves E (Unidade Local Saude Alto Minho, Portugal), Gonzalez L (Hospital Universitario Marques de Valdecilla, Santander, Spain),Grane N (Hospital General de Vic, Spain), Grigoriadis C (University of Athens, Aretaieion Hospital, Greece), Gutierrez L (Hospital Universitario Nuestra Señora de Valme, Spain), Haidopoulos D (Alexandra Hospital, Athens, Greece), Herraiz N (Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain), Irslinger E (UFK Tuebingen, Germany), Iyibozkurt A (Istanbul Faculty of Medicine, Istanbul University, Turkey), Joigneau L (Hospital de Fuenlabrada, Madrid, Spain), Karlsson H (Hospital Virgen del Camino, Pamplona, Spain), Kondi-Pafiti A (Aretaieion University Hospital, Athens, Greece), Mardas M (Poznan University of Medical Sciences, Poland), Marino M (Complejo Hospitalario de Caceres, Spain), Martinez A (Hospital de Sant Pau i Santa Tecla, Tarragona, Spain), Martinez C (Hospital Son Dureta, Mallorca, Spain), Martos MA (Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain), Menjon S (Hospital Universitario Virgen de las Nieves, Spain), Mitsopoulos V (Metaxa Memorial Cancer Hospital, Athens, Greece), Mora P (Hospital Clinico Universitario, Valladolid, Spain), Morales S (Hospital de Poniente, Spain), Moreno A (Hospital de la Linea de la Concepción, Spain), Nieto A (Complejo Hospitalario de Caceres, Spain), Novo A (Complejo Hospitalario Santiago de Compostela, Spain), Oehler M (Royal Adelaide Hospital, Adelaide), Otero M (Complejo Hospitalario de Leon, Spain), Papatheodorou DC, (Metaxa Memorial Cancer Hospital, Athens, Greece), Perez I (Fundacion Jimenez Diaz, Madrid, Spain), Piek J (VU University Medical Center, Amsterdam, The Netherlands), Polterauer S (Medical University of Vienna, Austria), Prado A (Hospital Costa del Sol, Marbella, Spain), Reula MC (Hospital de Santa Creu i Sant Pau, Spain), Robles M (Complejo Hospitalario de Pontevedra, Spain), Romeo M (Hospital Universitario Germans Trias i Pujol, Spain), Rosado C (Hospital de Mataro, Barcelona, Spain), Rubio P (Hospital Universitario Miguel Servet, Zaragoza, Spain), Rzepka J (MSC Memorial Cancer Center Warsaw, Poland), Sanz R (Fundacion Jimenez Diaz, Madrid, Spain), Sehouli J (Charité, Campus Virchow Clinic, University Hospital, Berlin, Germany), Soler C (Hospital de Santa Creu i Sant Pau, Spain), Sukhin V (Grigoriev Institute of Medical Radiology, Ukraine), Tsolakidis D (General Hospital Papageorgiou, Greece), Vieira-Baptista P (Hospital de Sao Joao, Portugal), Yildirim Y (Ege Gynaecology Training and Research Hospital, Izmir, Turkey), Zuñiga MA (Complejo Hospitalario Torrecardenas, Almeria, Spain).

    • Contributors This publication does not include any figures or tables from any other publications.

    • Funding The Spanish Society of Obstetrics and Gynecology partially funded the online database used for data collection.

    • Disclaimer No other funding agency or sponsor played a role in the design or performance of the study, including the collection, management, analysis, and interpretation of the data, and preparation, review, and approval of the report.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.