Association of Topical Corticosteroids With Reduced Vulvar Squamous Cell Carcinoma Recurrence in Patients With Vulvar Lichen Sclerosus | Dermatology | JAMA Dermatology | JAMA Network
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Table.  Recurrence of vSCC or dVIN in Patients With Vulvar Lichen Sclerosus Who Were Treated and Adhered to Topical Corticosteroid Therapy
Recurrence of vSCC or dVIN in Patients With Vulvar Lichen Sclerosus Who Were Treated and Adhered to Topical Corticosteroid Therapy
1.
Halonen  P, Jakobsson  M, Heikinheimo  O, Riska  A, Gissler  M, Pukkala  E.  Lichen sclerosus and risk of cancer.   Int J Cancer. 2017;140(9):1998-2002. doi:10.1002/ijc.30621 PubMedGoogle ScholarCrossref
2.
Bleeker  MC, Visser  PJ, Overbeek  LI, van Beurden  M, Berkhof  J.  Lichen sclerosus: incidence and risk of vulvar SCC.   Cancer Epidemiol Biomarkers Prev. 2016;25(8):1224-1230. doi:10.1158/1055-9965.EPI-16-0019 PubMedGoogle ScholarCrossref
3.
Lee  A, Bradford  J, Fischer  G.  Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women.   JAMA Dermatol. 2015;151(10):1061-1067. doi:10.1001/jamadermatol.2015.0643 PubMedGoogle ScholarCrossref
4.
Regauer  S.  Residual anogenital lichen sclerosus after cancer surgery has a high risk for recurrence: a clinicopathological study of 75 women.   Gynecol Oncol. 2011;123(2):289-294. doi:10.1016/j.ygyno.2011.07.010 PubMedGoogle ScholarCrossref
5.
Yap  JK, Fox  R, Leonard  S,  et al.  Adjacent lichen sclerosis predicts local recurrence and second field tumour in women with vulvar squamous cell carcinoma.   Gynecol Oncol. 2016;142(3):420-426. doi:10.1016/j.ygyno.2016.06.019 PubMedGoogle ScholarCrossref
6.
Pounds  R, Tahir  S, Dawson  C, Woodman  C, Luesley  D, Yap  J.  A survey on the use of topical steroids in patients treated for lichen sclerosus–associated vulval squamous cell carcinoma.   J Obstet Gynaecol. 2018;38(2):265-269. doi:10.1080/01443615.2017.1352572 PubMedGoogle ScholarCrossref
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    Research Letter
    May 6, 2020

    Association of Topical Corticosteroids With Reduced Vulvar Squamous Cell Carcinoma Recurrence in Patients With Vulvar Lichen Sclerosus

    Author Affiliations
    • 1St Vincent’s Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia
    • 2Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
    • 3Royal North Shore Hospital, Sydney, New South Wales, Australia
    • 4New South Wales Health Pathology, John Hunter Hospital, Newcastle, New South Wales, Australia
    • 5Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
    JAMA Dermatol. 2020;156(7):813-814. doi:10.1001/jamadermatol.2020.1074

    Vulvar lichen sclerosus (vLS), if untreated, results in a 5% to 7% increased lifetime incidence of vulvar squamous cell carcinoma (vSCC) and differentiated vulvar intraepithelial neoplasia (dVIN).1,2 This incidence rate can be reduced by suppressive topical corticosteroid treatment3; however, whether topical corticosteroid therapy can also reduce the rate of vSCC recurrence remains unknown. Current data report a 5-year rate of recurrence of 44% to 47% after surgical treatment.4,5 Furthermore, if a patient had 1 recurrence, their chance of another recurrence within 5 years rises to 80%.5 Determining whether topical corticosteroid treatment after surgery can reduce the risk of recurrence is important because up to 25% of women with vLS report not being treated with topical corticosteroid after vSCC excision.6 If shown to have an association with preventing cancer recurrence, topical corticosteroid therapy could be readily implemented.

    Methods

    The recurrence rate of vSCC or dVIN in patients with vLS who received long-term topical corticosteroid therapy was investigated through a medical record review of a dermatogynecology practice in Sydney, Australia. The computerized database, presently containing 2410 patients with vLS, was set up in 2008 to undertake a prospective cohort study of vLS,3 and patients remain under surveillance. The study was approved by the ethics committee of North Shore Private Hospital in Sydney, Australia, and written informed consent was obtained from all participants. All patients were treated with topical corticosteroids after primary excision of vSCC or dVIN. Agents used included betamethasone dipropionate, 0.05%, methylprednisolone aceponate, 0.1%, hydrocortisone, 1%, clobetasol propionate, 0.02% and 0.05%, and desonide, 0.05%. These agents were prescribed for daily application and titrated to a desired outcome of disease suppression, which was defined as skin of normal texture with loss of white discoloration. Patients were followed up at intervals of 3 to 12 months and were asked about adherence to the drug regimen using a 5-point Likert scale from 0 (not at all) to 5 (every specified day). Adherence was defined as a score of 4 (most days) or 5 (every specified day). Recurrence was defined as new dVIN or vSCC in a region of tissue where dVIN or vSCC had been previously excised with clear margins.

    Results

    From January 1, 2008, to April 30, 2019, the medical records of 25 patients with vLS and previous vSCC and/or dVIN were reviewed. Ten patients with human papillomavirus (HPV)–associated dVIN or HPV-associated vSCC were excluded. One patient who did not adhere to topical corticosteroid therapy and 3 patients with less than 5 years of follow-up (or loss to follow-up) were excluded. In the remaining 11 patients, mean age at diagnosis of primary lesion was 62.9 years (range, 26-88 years). Initial management of vSCC or dVIN included surgical excision alone in 4 patients, surgical excision with node biopsy in 2 patients, surgical excision with node dissection in 4 patients, and surgical excision with adjuvant laser therapy in 1 patient. Of 11 patients, 8 (73%) remained free of recurrence with a mean follow-up of 10.5 years (range, 5.1-16.5 years) (Table). Two patients (18%) had recurrence of their vSCC, 1 of whom developed multiple recurrences of vSCC, and 1 patient (9%) had recurrence of their dVIN.

    Discussion

    In the study cohort, patients with vLS who adhered to topical corticosteroid therapy had a vSCC or VIN recurrence rate of 27% compared with reported 5-year recurrence rates of 44% to 47%.4,5 Only 1 patient with a recurrence of vSCC or dVIN had a subsequent recurrence compared with the 5-year subsequent recurrence rate of 80% for untreated vLS.5 It has been hypothesized that chronic inflammation contributes to the increased risk of developing vSCC; thus, the anti-inflammatory effect of topical corticosteroid may confer a protective benefit.6 Topical corticosteroid treatment is inexpensive and safe3 and could result in considerable cost savings and reductions in morbidity and mortality.

    A limitation of the present study is that it is a single-center retrospective medical record review with a small sample size; there was no control group (patients not treated with a topical corticosteroid) for comparison. A strength of the study is that all included patients were part of a large cohort with vLS who have been followed up prospectively since 2008. Larger prospective studies including a control group for comparison would strengthen the evidence of the findings in this report.

    Topical corticosteroid therapy may represent an important management strategy to reduce the recurrence rate of vSCC and dVIN in patients with vLS. These findings suggest the need for a large prospective trial. However, in the meantime, we encourage dermatologists to play an active role in assisting colleagues who specialize in gynecology-oncology to use a topical corticosteroid when treating patients with vLS.

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    Article Information

    Accepted for Publication: March 6, 2020.

    Corresponding Author: Simone Chin, BMed, MD, St Vincent’s Clinical School, University of New South Wales, Victoria St, Darlinghurst, NSW 2010, Australia (simone.chin@health.nsw.gov.au).

    Published Online: May 6, 2020. doi:10.1001/jamadermatol.2020.1074

    Author Contributions: Drs Lee and Fischer are considered coauthors and contributed equally to this work. Drs Chin and Fischer had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Scurry, Bradford, Lee, Fischer.

    Acquisition, analysis, or interpretation of data: Chin, Lee, Fischer.

    Drafting of the manuscript: Chin, Lee, Fischer.

    Critical revision of the manuscript for important intellectual content: Scurry, Bradford, Lee, Fischer.

    Statistical analysis: Chin, Lee.

    Administrative, technical, or material support: Lee.

    Supervision: Lee, Fischer.

    Conflict of Interest Disclosures: None reported.

    References
    1.
    Halonen  P, Jakobsson  M, Heikinheimo  O, Riska  A, Gissler  M, Pukkala  E.  Lichen sclerosus and risk of cancer.   Int J Cancer. 2017;140(9):1998-2002. doi:10.1002/ijc.30621 PubMedGoogle ScholarCrossref
    2.
    Bleeker  MC, Visser  PJ, Overbeek  LI, van Beurden  M, Berkhof  J.  Lichen sclerosus: incidence and risk of vulvar SCC.   Cancer Epidemiol Biomarkers Prev. 2016;25(8):1224-1230. doi:10.1158/1055-9965.EPI-16-0019 PubMedGoogle ScholarCrossref
    3.
    Lee  A, Bradford  J, Fischer  G.  Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women.   JAMA Dermatol. 2015;151(10):1061-1067. doi:10.1001/jamadermatol.2015.0643 PubMedGoogle ScholarCrossref
    4.
    Regauer  S.  Residual anogenital lichen sclerosus after cancer surgery has a high risk for recurrence: a clinicopathological study of 75 women.   Gynecol Oncol. 2011;123(2):289-294. doi:10.1016/j.ygyno.2011.07.010 PubMedGoogle ScholarCrossref
    5.
    Yap  JK, Fox  R, Leonard  S,  et al.  Adjacent lichen sclerosis predicts local recurrence and second field tumour in women with vulvar squamous cell carcinoma.   Gynecol Oncol. 2016;142(3):420-426. doi:10.1016/j.ygyno.2016.06.019 PubMedGoogle ScholarCrossref
    6.
    Pounds  R, Tahir  S, Dawson  C, Woodman  C, Luesley  D, Yap  J.  A survey on the use of topical steroids in patients treated for lichen sclerosus–associated vulval squamous cell carcinoma.   J Obstet Gynaecol. 2018;38(2):265-269. doi:10.1080/01443615.2017.1352572 PubMedGoogle ScholarCrossref
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