Objective to evaluate the desire for parenthood and reproductive outcomes following fertility-sparing treatment for invasive cervical cancer including Vaginal Radical Trachelectomy (VRT), Radical Hysterectomy (RH) and chemoradiotherapy. Design Retrospective cohort study Setting Tertiary referral center in the Netherlands Population patients <45 years with invasive cervical cancer desiring to maintain reproductive potential. Methods Clinicopathologic and reproductive outcomes were retrieved from medical files and postal questionnaires for patients treated between 2009 – 2020. Main outcome measures Survival, recurrences, fertility and pregnancy outcomes Results 75 patients were identified of whom 34 underwent VRT, 9 RH and 32 had (chemo)radiotherapy. 26 patients started fertility preservation (FP) procedures of whom 23 (88.5%) successfully preserved fertility. After a median follow-up of 49 months, 5 patients developed recurrent disease and died. Reproductive outcomes were available for 58 patients of whom 89.6% maintained their desire for parenthood. Following VRT, 15 patients conceived 21 pregnancies which resulted in 15 live-births, yielding a pregnancy rate of 61.9% and live-birth rate of 75.0%. Following RH or (chemo)radiotherapy, 3 surrogate pregnancies were established (21.4%) using frozen-thawed oocytes (n=2) and ovarian tissue fragments (n=1) with good neonatal outcomes. Conclusions Many cervical cancer patients maintain the desire to become parents after cancer treatment. Vaginal Radical Trachelectomy and Fertility Preservation enable young women with invasive cervical cancer to become a parent after cancer treatment. Structural and timely fertility counseling is of the essence when attempting fertility-sparing treatment and should be available to all. Keywords cervical cancer / oncofertility / trachelectomy / fertility preservation / surrogacy

Objective To evaluate the influence of intrauterine (IU) or non-IU manipulators on oncological outcome in early-stage, low-grade endometrioid endometrial cancer (EEC). Design Retrospective cohort study Setting Nationwide population-based study in the Netherlands Population Women with FIGO stage I, low-grade EEC who received total laparoscopic hysterectomy between 2010 and 2020. Methods 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. Survival analyses were performed using univariable and multivariable cox regression analysis. Main outcome measures Recurrence of cancer, disease-free survival (DFS), overall survival (OS), site of recurrence, and manipulator preference according to type of hospital. Results Of the total study population (N = 5,205), 1524 (29.3%) patients underwent surgery in hospitals that used non-IU manipulators and 3681 (70.7%) in hospitals that used IU manipulators. Recurrence of cancer was experienced by 195 patients, 49 (3.2%) in the non-IU group and 146 (4.0%) in the IU group. No significant difference in site of recurrence was observed (p=0.778). After adjusting for potential confounders, type of uterus manipulator did not affect DFS (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.78–1.11) and OS (HR 0.90, 95% CI 0.75–1.09). Conclusion IU manipulators are not inferior to non-IU manipulators with respect to oncological outcome in early-stage, low-grade EEC.

Objective Effect on patient outcomes when introducing a novice robotic surgeon, trained in accordance with a structured learning curriculum, to an experienced robotic surgery team. Design Observational cohort study. Setting Tertiary referral centre. Population Patients with early-stage cervical cancer who were treated with primary robot-assisted surgery between 2007 and 2019. In addition to the 165 patients included in a former analysis, we included a further 61 consecutively treated patients and divided all patients over three groups: early learning phase of 61 procedures (group 1), experienced phase of the 104 procedures thereafter (group 2), and the final 61 procedures during introduction of a novice with structured training (group 3). Methods Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed and patient outcomes between groups were compared. Main Outcome Measures Surgical proficiency based on recurrence, surgical and oncological outcomes. Results Based on RA-CUSUM analysis, no learning curve effect was observed for group 3. Regarding surgical outcomes, mean operation time in group 3 was significantly shorter than group 1 ( p<0.001) and similar to group 2 ( p=0.96). Proportions of intraoperative and postoperative adverse events in group 3 were not significantly different from the experienced group (group 2). Regarding oncological outcomes, the 5-year disease-free survival, disease-specific survival, and overall survival in group 3 were not significantly different from the experienced group. Conclusions Introducing a novice robotic surgeon, who was trained in accordance with a structured learning curriculum, resulted in similar patient outcomes as by experienced surgeons suggesting novices can progress through a learning phase without compromising outcomes of cervical cancer patients.

Background Surgical treatment for high-grade cervical intraepithelial neoplasia (CIN) may affect future fertility and pregnancy outcomes, therefore alternative therapies are desirable. Objectives To determine the efficacy of topical imiquimod in treatment of high-grade CIN (defined as regression CIN 1 or less), and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared to surgical treatment and placebo. Search strategy Cohort studies and trials up to July 2022 were searched with the terms imiquimod, cervical dysplasia, and HPV. Selection criteria Studies evaluating the efficacy of imiquimod in CIN lesions. Data collection and analysis The study followed the PRISMA checklist. Meta-analysis was conducted to determine the efficacy of imiquimod treatment. Main results Five studies involving 463 women with high-grade CIN were included. Imiquimod was associated with histological regression to CIN1 or less in 55% of cases versus 29% for placebo, and 93% for surgical treatment. Imiquimod-treated women had a greater odds ratio of histological regression to CIN1 or less than placebo-treated women (ORs 4.17, 95% CI 2.03-8.54). In comparison to imiquimod, surgical treatment had an odds ratio of 14.81 (95% CI 6.59-33.27) for histological regression to CIN1 or less. The hr-HPV clearance rate was 53.4% after imiquimod treatment and 66% after surgical treatment (ORs 1.53, 95% CI 0.62-23.77). Conclusions: Histological regression is higher in imiquimod treatment than placebo. Surgical treatment, which is currently the golden standard, shows a higher regression rate than imiquimod. Future studies should focus on patient selection and further development of alternative treatments.

Background: Tumor positivity and upstaging rates from various surgical staging components performed in clinically early-stage epithelial ovarian carcinoma (EOC) vary widely in literature. Objectives: To quantify tumor positivity and upstaging rates for all staging surgery components in EOC patients. Differences between subgroups based on their clinical and histological characteristics are explored. Search strategy: A systematic search using synonyms of ‘ovarian cancer’, ‘neoplasm staging’, and ’neoplasm metastasis’ was conducted in PubMed, Embase, and the Cochrane Library. Selection criteria: Meta-analysis was performed on 23 included studies, comprising 5194 clinical stage I or II EOC patients who underwent comprehensive surgical staging. Data Collection and Analysis: Studies were assessed using the Newcastle-Ottawa Scale risk-of-bias tool. Pooled proportions and 95% confidence intervals were calculated using an inverse variance weighted random-effects model. Main Results: Overall upstaging rate of clinically early-stage EOC patients was 18.7% (95%CI: 14.1-23.4%). Serous histology or high grade EOC showed the highest upstaging rate at 35.3% (95%CI: 21.8-48.7%) and 40.9% (95%CI: 35.6-46.2%). Lymph node involvement resulted in an upstaging rate of 8.7% (95%CI: 6.2-11.3%). Tumor was identified in uterus, cytology, peritoneal biopsies, omentum and appendix in 6.2% (95%CI: 1.8-10.7%), 18.4% (95%CI: 13.8-22.9%), 9.7% (95%CI: 3.8-15.6%), 5.2% (95%CI: 1.7-8.8%) and 3.6% (95%CI: 0.0-7.5%) of EOC patients. The corresponding upstaging rates were 5.9% (95%CI: 1.4-10.4%), 8.5% (95%CI: 1.8-15.2%), 3.5% (95%CI: 1.0-6.0%), 3.9% (95%CI: 1.4-6.3%) and 1.6% (95%CI: 0.0-3.4%), respectively. Conclusion: The attributive value of comprehensive surgical staging in clinically early-stage EOC patients remains substantial, particularly in serous and high grade tumors.

Objective: To investigate the learning curve of robot-assisted laparoscopy in early stage cervical cancer and quantify impact on oncological outcomes. Design: Observational cohort study. Setting: Tertiary referral centre with one surgical team. Population: All early stage cervical cancer patients treated consecutively with robot-assisted laparoscopy between 2007 and 2017. Methods: With multivariate risk-adjusted cumulative sum analysis (RA-CUSUM), we assessed the learning curve of robot-assisted laparoscopy of a single surgical team based on cervical cancer recurrence. Subsequently, a survival analysis was conducted comparing oncological outcomes of patients treated during different phases of the learning curve. Main Outcome Measures: Surgical proficiency based on recurrence, survival rates in the different learning phases. Results: 165 cervical cancers patients were operated by robot-assisted laparoscopy, with a median follow-up of 57 months (range 3-132 months). The RA-CUSUM analysis demonstrated two phases of the learning curve: a learning phase of 61 procedures (group 1) and an experienced phase representing the 104 procedures thereafter (group 2). The 5-year disease free survival was 80.2% in group 1 and 91.1% in group 2 (P = 0.040). Both the 5-year disease-specific survival and overall survival significantly increased after the learning phase. Conclusion: The learning phase of robot-assisted laparoscopy in early stage cervical cancer in this institutional cohort is at least 61 procedures, with higher survival rates in the patients treated thereafter. The learning curve of robot-assisted laparoscopy affects oncological outcomes and warrants more attention in the design of future studies. Funding: None. Keywords: Cervical cancer, robot-assisted laparoscopy, learning curve, RA-CUSUM, recurrence, survival.