Advertisement

Margin status revisited in vulvar squamous cell carcinoma

      Highlights

      • Local recurrences occur in 43% of the vulvar cancer patients within ten years after treatment.
      • Pathologic tumor free margin distance had no effect on the local recurrence rate.
      • Patients with dVIN (with or without LS) in the margin have higher local recurrence rates.

      Abstract

      Objective

      To determine the incidence of local recurrence of vulvar squamous cell carcinoma in relation to tumor- and/or precursor lesion free pathologic margins.

      Methods

      Consecutive patients with primary vulvar squamous cell carcinoma surgically treated in two Dutch expert centers between 2000 and 2010 were included. All pathology slides were independently reviewed by two expert gynecopathologists, and local recurrence was defined as any recurrent disease located on the vulva. Time to first local recurrence was compared for different subgroups using univariable and multivariable Cox-regression analyses.

      Results

      In total 287 patients with a median follow-up of 80 months (range 0–204) were analyzed. The actuarial local recurrence rate ten years after treatment was 42.5%. Pathologic tumor free margin distance did not influence the risk on local recurrence (HR 1.03 (95% CI 0.99–1.06)), neither using a cutoff of eight, five, or three millimeters. Multivariable analyses showed a higher local recurrence rate in patients with dVIN and LS in the margin (HR 2.76 (95% CI 1.62–4.71)), in patients with dVIN in the margin (HR 2.14 (95% CI 1.11–4.12)), and a FIGO stage II or higher (HR 1.62 (95% CI 1.05–2.48)).

      Conclusions

      Local recurrences frequently occur in patients with primary vulvar carcinoma and are associated with dVIN (with or without LS) in the pathologic margin rather than any tumor free margin distance. Our results should lead to increased awareness among physicians of an ongoing risk for local recurrence and need for life-long follow-up. Intensified follow-up and treatment protocols for patients with dVIN in the margin should be evaluated in future research.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Gynecologic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Te Grootenhuis N.C.
        • van der Zee A.G.
        • van Doorn H.C.
        • van der Velden J.
        • Vergote I.
        • Zanagnolo V.
        • et al.
        Sentinel nodes in vulvar cancer: long-term follow-up of the GROningen INternational study on sentinel nodes in vulvar cancer (GROINSS-V) I.
        Gynecol. Oncol. 2016; 140: 8-14
        • Te Grootenhuis N.C.
        • Pouwer A.W.
        • de Bock G.H.
        • Hollema H.
        • Bulten J.
        • van der Zee A.G.J.
        • et al.
        Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: a systematic review.
        Gynecol. Oncol. 2018; 148: 622-631
        • The Royal College of Obstetricians & Gynaecologists
        Guidelines for the Diagnosis and Management of Vulval Carcinoma.
        2014
      1. National Comprehensive Cancer Network (NCCN Guidelines) Vulvar Cancer (Squamous Cell Carcinoma).

      2. European Society of Gynaecological Oncology, Vulvar Cancer Management Guidelines.

        • Nooij L.S.
        • van der Slot M.A.
        • Dekkers O.M.
        • Stijnen T.
        • Gaarenstroom K.N.
        • Creutzberg C.L.
        • et al.
        Tumour-free margins in vulvar squamous cell carcinoma: does distance really matter?.
        European journal of cancer (Oxford, England : 1990). 2016; 65: 139-149
        • Woelber L.
        • Griebel L.F.
        • Eulenburg C.
        • Sehouli J.
        • Jueckstock J.
        • Hilpert F.
        • et al.
        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.
        European journal of cancer (Oxford, England : 1990). 2016; 69: 180-188
        • Bornstein J.
        • Bogliatto F.
        • Haefner H.K.
        • Stockdale C.K.
        • Preti M.
        • Bohl T.G.
        • et al.
        The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions.
        Obstet. Gynecol. 2016; 127: 264-268
        • Yap J.K.
        • Fox R.
        • Leonard S.
        • Ganesan R.
        • Kehoe S.T.
        • Dawson C.W.
        • et al.
        Adjacent lichen sclerosis predicts local recurrence and second field tumour in women with vulvar squamous cell carcinoma.
        Gynecol. Oncol. 2016; 142: 420-426
        • Sznurkowski J.J.
        • Emerich J.
        Characteristic features of recurrences of squamous cell carcinoma of the vulva.
        Ginekol. Pol. 2010; 81: 12-19
        • Altman D.G.
        • McShane L.M.
        • Sauerbrei W.
        • Taube S.E.
        Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): explanation and elaboration.
        PLoS Med. 2012; 9e1001216
        • C B.V.
        Castor Electronic Data Capture. Amsterdam.
        2016
        • Wilkinson E.J.
        Superficial invasive carcinoma of the vulva.
        Clin. Obstet. Gynecol. 1985; 28: 188-195
        • Corp. I
        IBM SPSS Statistics for Windows. Version 25.0.
        IBM Corp, Armork, NY2017
        • Pouwer A.W. tGN
        • de Bock G.H.
        • Hollema H.
        • Bulten J.
        • van der Zee A.G.J.
        • de Hullu J.A.
        • Oonk M.H.M.
        Local Recurrence in Vulvar Carcinoma; Incidence and Prognostic Impact of Pathological Margin Distance and Lichen Sclerosus.
        International Journal of Gynecological Cancer. ESGO, Vienna2017: 2001
        • De Hullu J.A.
        • Hollema H.
        • Lolkema S.
        • Boezen M.
        • Boonstra H.
        • Burger M.P.
        • et al.
        Vulvar carcinoma. The price of less radical surgery.
        Cancer. 2002; 95: 2331-2338
        • van den Einden L.C.
        • de Hullu J.A.
        • Massuger L.F.
        • Grefte J.M.
        • Bult P.
        • Wiersma A.
        • et al.
        Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia.
        Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2013; 26: 874-880
        • Cooper S.M.
        • Madnani N.
        • Margesson L.
        Reduced risk of squamous cell carcinoma with adequate treatment of vulvar lichen sclerosus.
        JAMA dermatology. 2015; 151: 1059-1060
        • Lee A.
        • Bradford J.
        • Fischer G.
        Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women.
        JAMA dermatology. 2015; 151: 1061-1067
        • van de Nieuwenhof H.P.
        • van der Avoort I.A.
        • de Hullu J.A.
        Review of squamous premalignant vulvar lesions.
        Crit. Rev. Oncol. Hematol. 2008; 68: 131-156
        • Bleeker M.C.
        • Visser P.J.
        • Overbeek L.I.
        • van Beurden M.
        • Berkhof J.
        Lichen Sclerosus: incidence and risk of vulvar squamous cell carcinoma.
        Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research. 2016; 25 (cosponsored by the American Society of Preventive Oncology): 1224-1230
        • van de Nieuwenhof H.P.
        • Bulten J.
        • Hollema H.
        • Dommerholt R.G.
        • Massuger L.F.
        • van der Zee A.G.
        • et al.
        Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma.
        Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2011; 24: 297-305
        • McAlpine J.N.
        • Kim S.Y.
        • Akbari A.
        • Eshragh S.
        • Reuschenbach M.
        • von Knebel Doeberitz M.
        • et al.
        HPV-independent differentiated vulvar intraepithelial neoplasia (dVIN) is associated with an aggressive clinical course.
        International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists. 2017; 36: 507-516
        • Tantipalakorn C.
        • Robertson G.
        • Marsden D.E.
        • Gebski V.
        • Hacker N.F.
        Outcome and patterns of recurrence for International Federation of Gynecology and Obstetrics (FIGO) stages I and II squamous cell vulvar cancer.
        Obstet. Gynecol. 2009; 113: 895-901
        • Rouzier R.
        • Haddad B.
        • Plantier F.
        • Dubois P.
        • Pelisse M.
        • Paniel B.J.
        Local relapse in patients treated for squamous cell vulvar carcinoma: incidence and prognostic value.
        Obstet. Gynecol. 2002; 100: 1159-1167
        • Oonk M.H.
        • de Hullu J.A.
        • Hollema H.
        • Mourits M.J.
        • Pras E.
        • Wymenga A.N.
        • et al.
        The value of routine follow-up in patients treated for carcinoma of the vulva.
        Cancer. 2003; 98: 2624-2629
        • Nordin A.
        • Mohammed K.A.
        • Naik R.
        • de Barros Lopes A.
        • Monaghan J.
        Does long-term follow-up have a role for node negative squamous carcinoma of the vulva? The Gateshead experience.
        Eur. J. Gynaecol. Oncol. 2001; 22: 36-39