Topical imiquimod superior to surgery for vulvar intraepithelial neoplasia: Lancet

Austria: In a new study conducted by Gerda Trutnovsky and team, it was shown that Imiquimod is a secure, efficient, and well-accepted first-line therapy for patients with vulvar high-grade squamous intraepithelial lesions (vHSILs). The findings of this study were published in The Lancet.

It is difficult to handle vulvar high-grade squamous intraepithelial lesions optimally. Surgery is the conventional therapy, although 50% of patients experience recurrences. Although medical therapy with imiquimod is a successful option, the two methods have not been compared in a randomized study. As a result, this study compared the clinical efficacy, human papillomavirus (HPV) clearance, acceptability, histological response, and psychosexual morbidity of primary imiquimod therapy against surgical treatment in women with vHSIL.

The Austrian Gynecological Oncology group conducted this randomized, multicenter, phase 3, non-inferiority clinical trial at six sites in Austria. Female patients aged 18–90 years with histologically confirmed vHSIL with evident unifocal or multifocal lesions were recruited. Clinical suspicion of invasion, a history of vulvar malignancy or severe inflammatory dermatosis of the vulva, and any current therapy for vHSIL during the past 3 months were the main exclusion criteria.

Women with known immunodeficiency, who were pregnant, or who were nursing were not allowed to participate. Patients were randomly allocated (1:1) via block randomization to either imiquimod or surgery, and were stratified according to whether they had unifocal or multifocal illness. For 4–6 months, imiquimod was self-administered in a gradually ascending dose plan up to three times per week.

Excision or ablation were the procedures used in surgery. Vulvoscopy, vulvar biopsies, HPV testing, and patient-reported outcomes were used to evaluate patients at baseline, 6 months, and 12 months. The main outcome was full clinical response (CCR) 6 months after receiving local imiquimod therapy or undergoing one surgical operation. The primary analysis was performed in accordance with protocol, with a non-inferiority margin of 20%.

The key findings of this study were as follows:

1. Between June 7, 2013, and January 8, 2020, 110 patients with vHSIL were allocated at random.

2. Clinical response to therapy could be measured in 107 participants (54 in the imiquimod group and 53 in the surgery group), and the trial was completed by 98 patients (46 in the imiquimod group and 52 in the surgery group).

3. 37 (80%) of 46 imiquimod-treated patients had CCR, compared to 41 (79%) of 52 patients after one surgical operation, demonstrating non-inferiority of the novel therapy.

4. Invasive illness was discovered in five individuals during main or secondary surgery, but not in patients receiving imiquimod according to protocol.

5. There was no statistically significant difference between trial groups in terms of HPV clearance, side events, or treatment satisfaction.

Reference:

Trutnovsky, G., Reich, O., Joura, E. A., Holter, M., Ciresa-König, A., Widschwendter, A., Schauer, C., Bogner, G., Jan, Z., Boandl, A., Kalteis, M. S., Regauer, S., & Tamussino, K. (2022). Topical imiquimod versus surgery for vulvar intraepithelial neoplasia: a multicentre, randomised, phase 3, non-inferiority trial. In The Lancet. Elsevier BV. https://doi.org/10.1016/s0140-6736(22)00469-x