Clinical Research
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Prognostic Factors and Recurrence Patterns of Vulvar Cancer

Year 2025, Volume: 11 Issue: 3, 457 - 466, 29.09.2025
https://doi.org/10.53394/akd.1658502

Abstract

Objective: Vulvar cancer is a rare disease among gynecological cancers, mostly affecting postmenopausal women. The associated prognostic factors are not clear enough and the results in the studies are inconclusive due to rarity. We aimed to determine the impact of clinicopathological and therapeutic prognostic factors on the course of treatment and the patient's survival. The characteristics of recurrences, anatomic localization, and treatment strategies are also described.
Material and Methods: A total of 46 patients with clinicopathological diagnosis of squamous cell carcinoma of vulva who were treated at our tertiary care center between 2004 and 2021 were included in this retrospective cohort analysis study. Data on demographic, clinical and obstetric characteristics of patients at the time of initial diagnosis as well as tumor clinicopathologic features, treatment modalities, and oncological outcomes were recorded. Data were analyzed using Cox proportional hazards regression and Kaplan-Meier methods.
Results: The overall recurrence rate was 34.7% (n=16). The average median overall survival (OS), 5-year OS rate and median 5-year OS was 172 months, 63.6% and 51.9 months, respectively. Five-year progression-free survival rate was 71.7%. Patients experiencing recurrence demonstrating a notably shorter survival duration compared to those without recurrence (p<0.05). On logistic regression analysis receiving radiotherapy and neutrophil value were important prognostic factors for recurrence. The risk of recurrence in those who received radiotherapy was found to be 15 times higher compared to those who did not receive radiotherapy (OR = 15.032). The chance of recurrence rises by 0.05% (OR = 1.0005) for every unit increase in the neutrophil value.
Conclusion: Receiving radiotherapy is an important predictor of vulvar cancer recurrence.

Ethical Statement

The study was approved by the institutional ethics committee (Akdeniz University Clinical Research Ethics Committee - KAEK-854; date: 01.12.2021). Informed consent was obtained from each subject or their first-degree relatives (for the deceased ones).

Supporting Institution

none

Thanks

We would like to thank the staff of the Department of Pathology and the archives of our hospital who contributed to the digital recording of the patients' data. We are also grateful to the authors of the studies cited in this article.

References

  • 1. Miljanović-Špika I, Madunić MD, Topolovec Z, Kenjereš DK, Vidosavljević D. Prognostic Factors For Vulvar Cancer. Acta Clin Croat 2021; 60(1):25-32.
  • 2. Wohlmuth C, I Wohlmuth-Wieser. Vulvar malignancies: an interdisciplinary perspective. J Dtsch Dermatol Ges 2019; 17(12):1257-76.
  • 3. Weinberg D, RA Gomez-Martinez. Vulvar Cancer. Obstet Gynecol Clin North Am 2019; 46(1):125-35.
  • 4. Madeleine MM, Daling JR, Carter JJ, Wipf GC, Schwartz SM, McKnight B, Kurman RJ, Beckmann AM, Hagensee ME, Galloway DA. Cofactors with human papillomavirus in a population-based study of vulvar cancer. J Natl Cancer Inst 1997; 89(20):1516-23.
  • 5. Tan A, Bieber AK, Stein JA, Pomeranz MK. Diagnosis and management of vulvar cancer: A review. J Am Acad Dermatol 2019; 81(6):1387-96.
  • 6. Board, P.D.Q.A.T.E., Vulvar Cancer Treatment (PDQ®): Health Professional Version, in PDQ Cancer Information Summaries. 2002, National Cancer Institute (US): Bethesda (MD).
  • 7. Oonk MHM, Planchamp F, Baldwin P, Mahner S, Mirza MR, Fischerová D, Creutzberg CL, Guillot E, Garganese G, Lax S, Redondo A, Sturdza A, Taylor A, Ulrikh E, Vandecaveye V, van der Zee A, Wölber L, Zach D , Zannoni GF, Zapardiel I. European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer-Update 2023. Int J Gynecol Cancer 2023; 33(7):1023-43.
  • 8. Olawaiye AB, Cotler J, Cuello MA, Bhatla N, Okamoto A, Wilailak S, Purandare CN, Lindeque G, Berek JS, Kehoe S. FIGO staging for carcinoma of the vulva: 2021 revision. Int J Gynaecol Obstet 2021; 155(1):43-7.
  • 9. Chan JK, Sugiyama V, Pham H, Gu M, Rutgers J, Osann K, Cheung MK, Berman ML, Disaia PJ. Margin distance and other clinico-pathologic prognostic factors in vulvar carcinoma: a multivariate analysis. Gynecol Oncol 2007; 104(3):636-41.
  • 10. Woelber L, Mahner S, Voelker K, Zu Eulenburg C, Gieseking F, Choschzick M, Jaenicke F, Schwarz J. Clinicopathological prognostic factors and patterns of recurrence in vulvar cancer. Anticancer Res 2009; 29(2):545-52.
  • 11. Raspagliesi F, Hanozet F, Ditto A, Solima E, Zanaboni F, Vecchione F, Kusamura S. Clinical and pathological prognostic factors in squamous cell carcinoma of the vulva. Gynecol Oncol 2006; 102(2):333-7.
  • 12. Sun X, Zhang Y, Sun J, Feng S, Yan M, Cheng H. The comparative study of former and latest FIGO staging of vulva cancer. Minerva Chir 2012; 67(2):187-95.
  • 13. Woelber L, Griebel LF, Eulenburg C, Sehouli J, Jueckstock J, Hilpert F, de Gregorio N, Hasenburg A, Ignatov A, Hillemanns P, Fuerst S, Strauss HG, Baumann KH, Thiel FC, Mustea A, Meier W, Harter P, Wimberger P, Hanker LC, Schmalfeldt B, Canzler U, Fehm T, Luyten A, Hellriegel M, Kosse J, Heiss C, Hantschmann P, Mallmann P, Tanner B, Pfisterer J, Richter B, Neuser P, Mahner S. Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study. Eur J Cancer 2016; 69:180-88.
  • 14. Te Grootenhuis NC, Pouwer AW, de Bock GH, Hollema H, Bulten J, van der Zee AGJ, de Hullu JA, Oonk MHM. Margin status revisited in vulvar squamous cell carcinoma. Gynecol Oncol 2019; 154(2):266-275.
  • 15. Yang J, Delara R, Ghaith S, Newman H, Magrina J, Butler K, Kumar A, Dinh T, Chen L, Magtibay P. Tumor-free margins and local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 2020; 158(3):555-61.
  • 16. Paladini D, Cross P, Lopes A, Monaghan JM. Prognostic significance of lymph node variables in squamous cell carcinoma of the vulva. Cancer 1994; 74(9): p. 2491-6.
  • 17. Nicoletto MO, Parenti A, Bianco PD, Lombardi G, Pedrini L, Pizzi S, Carli P, Palma MD, Pastorelli D, Corti L, Becagli L. Vulvar cancer: prognostic factors. Anticancer Res 2010; 30(6):2311-7.
  • 18. Klapdor R, Hillemanns P, Wölber L, Jückstock J, Hilpert F, de Gregorio N, Hasenburg A, Sehouli J, Fürst S, Strauss H, Baumann K, Thiel F, Mustea A, Meier W, Harter P, Wimberger P, Hanker L, Schmalfeld B, Mahner S. Association between obesity and vulvar cancer recurrence: an analysis of the AGO-CaRE-1 study. Int J Gynecol Cancer 2020; 30(7):920-26.
  • 19. Baiocchi G, RM Rocha. Vulvar cancer surgery. Curr Opin Obstet Gynecol 2014; 26(1):9-17.
  • 20. Ioffe YJ, Erickson BK, Foster KE, Mutch DG, Powell MA, Thaker PH, Hagemann AR, Conner MG, Huh WK, Massad LS. Low yield of residual vulvar carcinoma and dysplasia upon re-excision for close or positive margins. Gynecol Oncol 2013; 129(3):528-32.
  • 21. Woelber L, Jaeger A, Prieske K. New treatment standards for vulvar cancer 2020. Curr Opin Obstet Gynecol 2020; 32(1):9-14.
  • 22. Heaps JM, Fu YS, Montz FJ, Hacker NF, Berek JS. Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 1990; 38(3):309-14.
  • 23. Faul CM, Mirmow D, Huang Q, Gerszten K, Day R , Jones MW. Adjuvant radiation for vulvar carcinoma: improved local control. Int J Radiat Oncol Biol Phys 1997; 38(2):381-9.
  • 24. Viswanathan AN, Pinto AP, Schultz D, Berkowitz R, Crum CP. Relationship of margin status and radiation dose to recurrence in post-operative vulvar carcinoma. Gynecol Oncol 2013; 130(3):545-9.
  • 25. Woelber L, Choschzick M, Eulenburg C, Hager M, Jaenicke F, Gieseking F, Kock L, Ihnen M, Petersen C, Schwarz J, Mahner S. Prognostic value of pathological resection margin distance in squamous cell cancer of the vulva. Ann Surg Oncol 2011; 18(13):3811-8.
  • 26. Nooij LS, van der Slot MA, Dekkers OM, Stijnen T, Gaarenstroom KN, Creutzberg CL, Smit VTHBM, Bosse T, van Poelgeest MIE. Tumour-free margins in vulvar squamous cell carcinoma: Does distance really matter? Eur J Cancer 2016; 65:139-49.
  • 27. Arvas M, Kahramanoglu I, Bese T, Turan H, Sozen I, Ilvan S, Demirkiran F. The Role of Pathological Margin Distance and Prognostic Factors After Primary Surgery in Squamous Cell Carcinoma of the Vulva. Int J Gynecol Cancer 2018; 28(3): 623-31.
  • 28. Milliken S, May J, Sanderson PA, Congiu MA, D'Oria O, D'Augè TG, Caruso G, DI Donato V, Panici PB, Giannini A. Reducing the radicality of surgery for vulvar cancer: are smaller margins safer? Minerva Obstet Gynecol 2021; 73(2): 160-65.
  • 29. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454(7203): 436-44.
  • 30. Zheng L, Zou K, Yang C, Chen F, Guo T, Xiong B. Inflammation-based indexes and clinicopathologic features are strong predictive values of preoperative circulating tumor cell detection in gastric cancer patients. Clin Transl Oncol 2017; 19(9): 1125-32.
  • 31. Bartl T, Bekos C, Postl M, Alexander R, Polterauer S, Stefanie A, Richard S. The systemic immune-inflammation index (SII) is an independent prognostic parameter of survival in patients with invasive vulvar cancer. J Gynecol Oncol 2021; 32(1): e1.
  • 32. Ertas IE, Gungorduk K, Akman L, Ozdemir A, Terek MC, Ozsaran A, Sanci M, Dikmen Y. Can preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios be used as predictive markers for lymph node metastasis in squamous cell carcinoma of the vulva? Eur J Obstet Gynecol Reprod Biol 2013; 171(1): 138-42.

Vulva Kanserinde Prognostik Faktörler ve Nüks Paternleri

Year 2025, Volume: 11 Issue: 3, 457 - 466, 29.09.2025
https://doi.org/10.53394/akd.1658502

Abstract

Amaç: Vulva kanseri, jinekolojik kanserler arasında nadir görülen bir hastalık olup, çoğunlukla postmenopozal kadınları etkilemektedir. İlişkili prognostik faktörler yeterince net değildir ve çalışmalardaki sonuçlar, hastalığın nadir görülmesi nedeniyle kesinlik taşımamaktadır. Klinikopatolojik ve terapötik prognostik faktörlerin tedavi süreci ve hasta sağ kalımı üzerindeki etkisini belirlemeyi amaçladık. Nükslerin özellikleri, anatomik lokalizasyonu ve tedavi stratejileri de detaylandırılmıştır.
Gereç ve Yöntemler: Bu retrospektif kohort analizine, 2004–2021 yılları arasında üçüncü basamak sağlık merkezimizde tedavi edilmiş ve klinikopatolojik olarak vulvar skuamöz hücreli karsinom tanısı almış toplam 46 hasta dahil edilmiştir. Hastaların ilk tanı anındaki demografik, klinik ve obstetrik özelliklerinin yanı sıra tümörün klinikopatolojik özellikleri, tedavi modaliteleri ve onkolojik sonuçlarına ilişkin veriler kaydedilmiştir. Veriler, Cox regresyon analizi ve Kaplan-Meier yöntemleri kullanılarak analiz edilmiştir.
Bulgular: Genel nüks oranı %34,7 (n=16) olarak bulunmuştur. Ortalama medyan genel sağ kalım (OS), 5 yıllık OS oranı ve medyan 5 yıllık OS sırasıyla 172 ay, %63,6 ve 51,9 ay olarak hesaplanmıştır. Beş yıllık progresyonsuz sağ kalım oranı %71,7 olarak belirlenmiştir. Nüks olan hastalar, nüks olmayanlara kıyasla belirgin şekilde daha kısa bir sağ kalım süresine sahiptir (p<0,05). Lojistik regresyon analizine göre radyoterapi alımı ve nötrofil değeri, nüks için önemli prognostik faktörler olarak belirlenmiştir. Radyoterapi alan bireylerde nüks riskinin, radyoterapi almayanlara kıyasla 15 kat daha yüksek olduğu tespit edilmiştir (OR = 15,032). Nötrofil değerindeki her bir birimlik artış, nüks olasılığını %0,05 oranında artırmaktadır (OR = 1,0005).
Sonuç: Radyoterapi alımı, vulva kanseri nüksü için önemli bir belirleyicidir.

References

  • 1. Miljanović-Špika I, Madunić MD, Topolovec Z, Kenjereš DK, Vidosavljević D. Prognostic Factors For Vulvar Cancer. Acta Clin Croat 2021; 60(1):25-32.
  • 2. Wohlmuth C, I Wohlmuth-Wieser. Vulvar malignancies: an interdisciplinary perspective. J Dtsch Dermatol Ges 2019; 17(12):1257-76.
  • 3. Weinberg D, RA Gomez-Martinez. Vulvar Cancer. Obstet Gynecol Clin North Am 2019; 46(1):125-35.
  • 4. Madeleine MM, Daling JR, Carter JJ, Wipf GC, Schwartz SM, McKnight B, Kurman RJ, Beckmann AM, Hagensee ME, Galloway DA. Cofactors with human papillomavirus in a population-based study of vulvar cancer. J Natl Cancer Inst 1997; 89(20):1516-23.
  • 5. Tan A, Bieber AK, Stein JA, Pomeranz MK. Diagnosis and management of vulvar cancer: A review. J Am Acad Dermatol 2019; 81(6):1387-96.
  • 6. Board, P.D.Q.A.T.E., Vulvar Cancer Treatment (PDQ®): Health Professional Version, in PDQ Cancer Information Summaries. 2002, National Cancer Institute (US): Bethesda (MD).
  • 7. Oonk MHM, Planchamp F, Baldwin P, Mahner S, Mirza MR, Fischerová D, Creutzberg CL, Guillot E, Garganese G, Lax S, Redondo A, Sturdza A, Taylor A, Ulrikh E, Vandecaveye V, van der Zee A, Wölber L, Zach D , Zannoni GF, Zapardiel I. European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer-Update 2023. Int J Gynecol Cancer 2023; 33(7):1023-43.
  • 8. Olawaiye AB, Cotler J, Cuello MA, Bhatla N, Okamoto A, Wilailak S, Purandare CN, Lindeque G, Berek JS, Kehoe S. FIGO staging for carcinoma of the vulva: 2021 revision. Int J Gynaecol Obstet 2021; 155(1):43-7.
  • 9. Chan JK, Sugiyama V, Pham H, Gu M, Rutgers J, Osann K, Cheung MK, Berman ML, Disaia PJ. Margin distance and other clinico-pathologic prognostic factors in vulvar carcinoma: a multivariate analysis. Gynecol Oncol 2007; 104(3):636-41.
  • 10. Woelber L, Mahner S, Voelker K, Zu Eulenburg C, Gieseking F, Choschzick M, Jaenicke F, Schwarz J. Clinicopathological prognostic factors and patterns of recurrence in vulvar cancer. Anticancer Res 2009; 29(2):545-52.
  • 11. Raspagliesi F, Hanozet F, Ditto A, Solima E, Zanaboni F, Vecchione F, Kusamura S. Clinical and pathological prognostic factors in squamous cell carcinoma of the vulva. Gynecol Oncol 2006; 102(2):333-7.
  • 12. Sun X, Zhang Y, Sun J, Feng S, Yan M, Cheng H. The comparative study of former and latest FIGO staging of vulva cancer. Minerva Chir 2012; 67(2):187-95.
  • 13. Woelber L, Griebel LF, Eulenburg C, Sehouli J, Jueckstock J, Hilpert F, de Gregorio N, Hasenburg A, Ignatov A, Hillemanns P, Fuerst S, Strauss HG, Baumann KH, Thiel FC, Mustea A, Meier W, Harter P, Wimberger P, Hanker LC, Schmalfeldt B, Canzler U, Fehm T, Luyten A, Hellriegel M, Kosse J, Heiss C, Hantschmann P, Mallmann P, Tanner B, Pfisterer J, Richter B, Neuser P, Mahner S. Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study. Eur J Cancer 2016; 69:180-88.
  • 14. Te Grootenhuis NC, Pouwer AW, de Bock GH, Hollema H, Bulten J, van der Zee AGJ, de Hullu JA, Oonk MHM. Margin status revisited in vulvar squamous cell carcinoma. Gynecol Oncol 2019; 154(2):266-275.
  • 15. Yang J, Delara R, Ghaith S, Newman H, Magrina J, Butler K, Kumar A, Dinh T, Chen L, Magtibay P. Tumor-free margins and local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 2020; 158(3):555-61.
  • 16. Paladini D, Cross P, Lopes A, Monaghan JM. Prognostic significance of lymph node variables in squamous cell carcinoma of the vulva. Cancer 1994; 74(9): p. 2491-6.
  • 17. Nicoletto MO, Parenti A, Bianco PD, Lombardi G, Pedrini L, Pizzi S, Carli P, Palma MD, Pastorelli D, Corti L, Becagli L. Vulvar cancer: prognostic factors. Anticancer Res 2010; 30(6):2311-7.
  • 18. Klapdor R, Hillemanns P, Wölber L, Jückstock J, Hilpert F, de Gregorio N, Hasenburg A, Sehouli J, Fürst S, Strauss H, Baumann K, Thiel F, Mustea A, Meier W, Harter P, Wimberger P, Hanker L, Schmalfeld B, Mahner S. Association between obesity and vulvar cancer recurrence: an analysis of the AGO-CaRE-1 study. Int J Gynecol Cancer 2020; 30(7):920-26.
  • 19. Baiocchi G, RM Rocha. Vulvar cancer surgery. Curr Opin Obstet Gynecol 2014; 26(1):9-17.
  • 20. Ioffe YJ, Erickson BK, Foster KE, Mutch DG, Powell MA, Thaker PH, Hagemann AR, Conner MG, Huh WK, Massad LS. Low yield of residual vulvar carcinoma and dysplasia upon re-excision for close or positive margins. Gynecol Oncol 2013; 129(3):528-32.
  • 21. Woelber L, Jaeger A, Prieske K. New treatment standards for vulvar cancer 2020. Curr Opin Obstet Gynecol 2020; 32(1):9-14.
  • 22. Heaps JM, Fu YS, Montz FJ, Hacker NF, Berek JS. Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 1990; 38(3):309-14.
  • 23. Faul CM, Mirmow D, Huang Q, Gerszten K, Day R , Jones MW. Adjuvant radiation for vulvar carcinoma: improved local control. Int J Radiat Oncol Biol Phys 1997; 38(2):381-9.
  • 24. Viswanathan AN, Pinto AP, Schultz D, Berkowitz R, Crum CP. Relationship of margin status and radiation dose to recurrence in post-operative vulvar carcinoma. Gynecol Oncol 2013; 130(3):545-9.
  • 25. Woelber L, Choschzick M, Eulenburg C, Hager M, Jaenicke F, Gieseking F, Kock L, Ihnen M, Petersen C, Schwarz J, Mahner S. Prognostic value of pathological resection margin distance in squamous cell cancer of the vulva. Ann Surg Oncol 2011; 18(13):3811-8.
  • 26. Nooij LS, van der Slot MA, Dekkers OM, Stijnen T, Gaarenstroom KN, Creutzberg CL, Smit VTHBM, Bosse T, van Poelgeest MIE. Tumour-free margins in vulvar squamous cell carcinoma: Does distance really matter? Eur J Cancer 2016; 65:139-49.
  • 27. Arvas M, Kahramanoglu I, Bese T, Turan H, Sozen I, Ilvan S, Demirkiran F. The Role of Pathological Margin Distance and Prognostic Factors After Primary Surgery in Squamous Cell Carcinoma of the Vulva. Int J Gynecol Cancer 2018; 28(3): 623-31.
  • 28. Milliken S, May J, Sanderson PA, Congiu MA, D'Oria O, D'Augè TG, Caruso G, DI Donato V, Panici PB, Giannini A. Reducing the radicality of surgery for vulvar cancer: are smaller margins safer? Minerva Obstet Gynecol 2021; 73(2): 160-65.
  • 29. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454(7203): 436-44.
  • 30. Zheng L, Zou K, Yang C, Chen F, Guo T, Xiong B. Inflammation-based indexes and clinicopathologic features are strong predictive values of preoperative circulating tumor cell detection in gastric cancer patients. Clin Transl Oncol 2017; 19(9): 1125-32.
  • 31. Bartl T, Bekos C, Postl M, Alexander R, Polterauer S, Stefanie A, Richard S. The systemic immune-inflammation index (SII) is an independent prognostic parameter of survival in patients with invasive vulvar cancer. J Gynecol Oncol 2021; 32(1): e1.
  • 32. Ertas IE, Gungorduk K, Akman L, Ozdemir A, Terek MC, Ozsaran A, Sanci M, Dikmen Y. Can preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios be used as predictive markers for lymph node metastasis in squamous cell carcinoma of the vulva? Eur J Obstet Gynecol Reprod Biol 2013; 171(1): 138-42.
There are 32 citations in total.

Details

Primary Language English
Subjects Gynecologic Oncology Surgery, Obstetrics and Gynaecology
Journal Section Research Article
Authors

Saliha Sağnıç 0000-0002-5440-2940

Hasan Aykut Tuncer 0000-0002-5434-1025

Selen Dogan 0000-0002-4019-5581

Tayup Şimşek 0000-0003-1088-3970

Early Pub Date September 22, 2025
Publication Date September 29, 2025
Submission Date March 15, 2025
Acceptance Date April 28, 2025
Published in Issue Year 2025 Volume: 11 Issue: 3

Cite

Vancouver Sağnıç S, Tuncer HA, Dogan S, Şimşek T. Prognostic Factors and Recurrence Patterns of Vulvar Cancer. Akd Med J. 2025;11(3):457-66.