Cornelis G. Gerestein

Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC‐2): A randomised controlled trial

AbstractObjectiveTo investigate the efficacy of imiquimod in women with residual or recurrent cervical intraepithelial neoplasia (rrCIN), compared with large loop excision of the transformation zone (LLETZ).DesignRandomised controlled non‐inferiority trial.SettingOne academic and one regional hospital in the Netherlands.PopulationThirty‐five women with rrCIN were included in the study between May 2016 and May 2021.MethodsWomen were randomised to receive treatment with 5% imiquimod cream (12.5 mg) intravaginally (three times a week for a duration of 16 weeks) or a LLETZ procedure (standard treatment).Main outcome measuresThe primary outcome was reduction to normal cytology at 6 months after starting treatment. Secondary outcomes were clearance of high‐risk human papilloma virus (hr‐HPV) in both groups and reduction to ≤CIN1 in the imiquimod group. Side effects were monitored.ResultsTreatment success was 33% (6/18) in the imiquimod group versus 100% (16/16) in the LLETZ group (P < 0.001), whereas HPV clearance was 22% (4/18) in the imiquimod group versus 88% (14/16) in the LLETZ group (P < 0.001). After the randomisation of 35 women, the futility of treatment with imiquimod was proven and the trial was prematurely finished. In the follow‐up period, three patients remained without additional treatment, whereas all other patients underwent LLETZ, conisation or hysterectomy. In the LLETZ group none of the patients received additional treatment during 2 years of follow‐up.ConclusionsThis is the first randomised controlled trial to show that topical imiquimod has a significantly lower success rate in terms of reduction to normal cytology and hr‐HPV clearance, compared with LLETZ, in women with rrCIN. Additionally, imiquimod has numerous side effects and after using imiquimod most women with rrCIN still required additional surgical treatment.

Effect of uterine manipulator on oncologic outcome in early-stage, low-grade endometrial cancer.

To evaluate the influence of intrauterine manipulators on oncological outcomes in early-stage, low-grade endometrioid endometrial cancer. This retrospective, nationwide population-based study included all women International Federation of Gynecology and Obstetrics stage I, low-grade endometrioid endometrial cancer who underwent total laparoscopic hysterectomy between January 2010 and December 2020 in the Netherlands. Patient data were identified from the Netherlands Cancer Registry. Data regarding hospital manipulator preferences were retrieved through an online survey. Patients were categorized based on hospital manipulator preference. Main outcome measures were recurrence of cancer, disease-free survival, overall survival, site of recurrence, and manipulator preference according to the type of hospital. Survival analyses were performed using univariable and multivariable Cox regression analysis. Of the total study population (N = 5205), 1524 (29.3%) patients underwent surgery in hospitals that preferred no intrauterine manipulators and 3681 (70.7%) in hospitals that demonstrated a preference for intrauterine manipulators. Cancer recurrence was seen in 195 patients, 49 (3.2%) in the non-intrauterine group and 146 (4.0%) in the intrauterine group. (p =.78) After adjusting for potential confounders, the type of uterus manipulator did not affect disease-free survival (HR 0.93, 95% CI 0.78 to 1.11) and overall survival (HR 0.90, 95% CI 0.75 to 1.09). Intrauterine manipulators were not associated with higher recurrence rates in early-stage, low-grade endometrioid endometrial cancer.