Prognostic value of molecular classification in stage IV endometrial cancer.

OBJECTIVES: Multiple studies have proven the prognostic value of molecular classification for stage I-III endometrial cancer patients. However, studies on the relevance of molecular classification for stage IV endometrial cancer patients are lacking. Hypothetically, poor prognostic molecular subtypes are more common in higher stages of endometrial cancer. Considering the poor prognosis of stage IV endometrial cancer patients, it is questionable whether molecular classification has additional prognostic value. Therefore, we determined which molecular subclasses are found in stage IV endometrial cancer and if there is a correlation with progression-free and overall survival. METHODS: A retrospective multicenter cohort study was conducted using data from five Dutch hospitals. Patients with stage IV endometrial cancer at diagnosis who were treated with primary cytoreductive surgery or cytoreductive surgery after induction chemotherapy between January 2000 and December 2018 were included. Exclusion criteria were age <18 years or recurrent disease. The molecular classification was performed centrally on all tumor samples according to the World Health Organization 2020 classification (including POLE and estrogen receptor status). The Kaplan-Meier method was used to calculate progression free and overall survival in the molecular subclasses, for the different histological subtypes and for estrogen receptor positive versus estrogen receptor negative tumors. Groups were compared using the log-rank test. RESULTS: 164 stage IV endometrial cancer patients were molecularly classified. Median age of the patients was 67 years (range 33-86). Most patients presented with a non-endometrioid histological subtype (58%). Intra-abdominal complete cytoreductive surgery was achieved in 60.4% of the patients. 101 tumors (61.6%) were classified as p53 abnormal, 35 (21.3%) as no specific molecular profile, 21 (12.8%) as mismatch repair deficient, and 6 (3%) as POLE mutated. Molecular classification had no significant impact on progression free (p=0.056) or overall survival (p=0.12) after cytoreductive surgery. Overall survival was affected by histologic subtype (p<0.0001) and estrogen receptor status (p=0.013). CONCLUSION: The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I-III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions.

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

OBJECTIVE: To 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). DESIGN: Randomised controlled non-inferiority trial. SETTING: One academic and one regional hospital in the Netherlands. POPULATION: Thirty-five women with rrCIN were included in the study between May 2016 and May 2021. METHODS: Women 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 MEASURES: The 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. RESULTS: Treatment 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. CONCLUSIONS: This 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.

Symptomatic Lymphocele After Robot-Assisted Pelvic Lymphadenectomy as Part of the Primary Surgical Treatment for Cervical and Endometrial Cancer: A Retrospective Cohort Study.

STUDY OBJECTIVES: Pelvic lymph node dissection (PLND) is part of the primary treatment for early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer. Pelvic lymphocele is a postoperative complication of PLND, and when symptomatic, lymphoceles necessitate treatment. The aim of this study was to investigate the incidence and risk factors of symptomatic lymphocele after robot-assisted laparoscopic PLND in cervical and endometrial cancer. DESIGN: Retrospective cohort study. SETTING: Single-center academic hospital. PATIENTS: Two hundred and fifty-eight patients with cervical cancer and 129 patients with endometrial cancer. INTERVENTIONS: Pelvic lymphadenectomy by robot-assisted laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: The authors retrospectively included all patients with early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer who underwent pelvic lymphadenectomy by robot-assisted laparoscopic surgery between 2008 and 2022. Medical records were reviewed for the occurrence of a symptomatic lymphocele. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for developing a symptomatic lymphocele. In total, 387 patients, 258 with cervical cancer and 129 with endometrial cancer, were included in the study. The overall incidence of symptomatic lymphoceles was 9.6% with a median follow-up of 47 months [interquartile range 23-61]. For the entire cohort, smoking was the only significant risk factor for symptomatic lymphoceles identified in univariate (OR 2.47, 95% CI 1.19-5.11) and multivariate analysis (OR 2.42, 95% CI 1.16-5.07). For cervical cancer, body mass index (BMI) (OR 1.09, 95% CI 1.00-1.17) and prior abdominal surgery (OR 2.75, 95% CI 1.22-6.17) were also identified as significant independent risk factors. For endometrial cancer, age was identified as a significant independent risk factor (OR 0.90, 95% CI 0.83-0.97). CONCLUSION: This single-center cohort study demonstrated an incidence of almost 10% of symptomatic lymphoceles after robot-assisted laparoscopic PLND for cervical cancer and endometrial cancer, with a higher risk observed among patients who smoke at the time of diagnosis. Furthermore, risk factors differ between the 2 populations, necessitating further studies to establish risk models.

Introducing a novice surgeon to an experienced robotic gynaecological oncology team: An observational cohort study on the impact of a structured curriculum on outcomes of cervical cancer surgery.

OBJECTIVE: To evaluate the effect on patient outcomes when introducing a novice robotic surgeon, trained in accordance with a structured learning curriculum, to an experienced robotic surgery team treating cervical cancer patients. METHODS: Patients with early-stage cervical cancer who were treated with primary robot-assisted surgery between 2007 and 2019 were retrospectively included. In addition to the 165 patients included in a former analysis, we included a further 61 consecutively treated patients and divided all 226 patients over three groups: early learning phase of 61 procedures without structured training (group 1), experienced phase of 104 procedures (group 2), and the 61 procedures during introduction of a novice with structured training (group 3). Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to assess the learning curve effect. Patient outcomes between the groups were compared. 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.

Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Patient Characteristics, Treatment, and Outcome-A Systematic Review.

BACKGROUND: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare aggressive ovarian malignancy mainly affecting children, adolescents, and young adults. Since the discovery of mutations in the SMARCA4 gene in 2014, SCCOHT has become the subject of extensive investigation. However, international uniform treatment guidelines for SCCOHT are lacking and the outcome remains poor. The aim of this systematic review is to generate an overview of all reported patients with SCCOHT from 1990 onwards, describing the clinical presentation, genetic characteristics, treatment, and outcome. METHODS: A systematic search was performed in the databases Embase, Medline, Web of Science, and Cochrane for studies that focus on SCCOHT. Patient characteristics and treatment data were extracted from the included studies. Survival was estimated using Kaplan-Meier's methodology. To assess the difference between survival, the log-rank test was used. To quantify the effect of the FIGO stage, the Cox proportional hazard regression model was estimated. The chi-squared test was used to study the association between the FIGO stage and the surgical procedures. RESULTS: Sixty-seven studies describing a total of 306 patients were included. The median patient age was 25 years (range 1-60 years). The patients mostly presented with non-specific symptoms such as abdominal pain and sometimes showed hypercalcemia and elevated CA-125. A great diversity in the diagnostic work-up and therapeutic approaches was reported. The chemotherapy regimens were very diverse, all containing a platinum-based (cisplatin or carboplatin) backbone. Survival was strongly associated with the FIGO stage at diagnosis. CONCLUSIONS: SCCOHT is a rare and aggressive ovarian cancer, with a poor prognosis, and information on adequate treatment for this cancer is lacking. The testing of mutations in SMARCA4 is crucial for an accurate diagnosis and may lead to new treatment options. Harmonization and international collaboration to obtain high-quality data on diagnostic investigations, treatment, and outcome are warranted to be able to develop international treatment guidelines to improve the survival chances of young women with SCCOHT.

Learning curve and factors influencing successful robot-assisted bilateral sentinel lymph node mapping in early-stage cervical cancer: an observational cohort study.

OBJECTIVES: To evaluate whether a learning curve affects the bilateral sentinel lymph node (SLN) detection in early-stage cervical cancer. METHODS: All patients with FIGO (2018) stage IA1-IB2 or IIA1 cervical cancer who had undergone robot-assisted SLN mapping performed with a combination of preoperative technetium-99m nanocolloids (including preoperative imaging) and intraoperative blue dye were retrospectively included. Risk-adjusted cumulative sum (RA-CUSUM) analysis was used to determine if a learning curve based on bilateral SLN detection existed in this cohort. RESULTS: A total of 227 cervical cancer patients were included. In 98.2% of patients (223/227) at least one SLN was detected. The bilateral SLN detection rate was 87.2% (198/227). Except for age (OR 1.06 per year, 95%CI 1.02-1.09), no significant risk factors for non-bilateral SLN detection were found (e.g., prior conization, BMI or FIGO stage). The RA-CUSUM analysis showed no clear learning phase during the first procedures and cumulative bilateral detection rate remained at least 80% during the entire inclusion period. CONCLUSIONS: In this single-institution experience, we observed no learning curve affecting robot-assisted SLN mapping using a radiotracer and blue dye in early-stage cervical cancer patients, with stable bilateral detection rates of at least 80% when adhering to a standardized methodology.

Fluorescent Indocyanine Green versus Technetium-99m and Blue Dye for Bilateral SENTinel Lymph Node Detection in Stage I-IIA Cervical Cancer (FluoreSENT): protocol for a non-inferiority study.

INTRODUCTION: Nowadays, two predominant methods for detecting sentinel lymph nodes (SLNs) in cervical cancer are in use. The most conventional method is a combination of a radiotracer, technetium-99m (99mTc) and blue dye. More recently, another method for SLN mapping using indocyanine green (ICG) is becoming widely accepted. ICG is a fluorescent dye, visualised intraoperatively with near-infrared (NIR) fluorescence imaging, providing real-time visual navigation. The presumed advantages of ICG over 99mTc, that is, being cheaper, non-radioactive and logistically more attractive, are only valuable if its detection rate proves to be at least non-inferior. Before omitting the well-functioning and evidence-based combined approach of 99mTc and blue dye, we aim to provide prospective evidence on the non-inferiority of ICG with NIR fluorescence imaging. METHODS AND ANALYSIS: We initiated a prospective non-inferiority study with a paired comparison of both SLN methods in a single sample of 101 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB2 or IIA1 cervical cancer receiving primary surgical treatment. All patients undergo SLN mapping with ICG and NIR fluorescence imaging in adjunct to mapping with 99mTc (including single photon emission computed tomography with X-ray computed tomography (SPECT/CT)) and blue dye. Surgeons start SLN detection with ICG while being blinded for the preoperative outcome of SPECT/CT to avoid biased detection with ICG. Primary endpoint of this study is bilateral SLN detection rate of both methods (ie, detection of at least one SLN in each hemipelvis). Since we compare strategies for SLN mapping that are already applied in current daily practice for different types of cancer, no additional risks or burdens are expected from these study procedures. ETHICS AND DISSEMINATION: The current study is approved by the Medical Ethics Research Committee Utrecht (reference number 21-014). Findings arising from this study will be disseminated in peer-reviewed journals, academic conferences and through patient organisations. TRIAL REGISTRATION NUMBER: NL9011 and EudraCT 2020-005134-15.

Mainstream genetic testing for women with ovarian cancer provides a solid basis for patients to make a well-informed decision about genetic testing.

BACKGROUND: There is a growing need for genetic testing of women with epithelial ovarian cancer. Mainstream genetic testing provides an alternative care pathway in which non-genetic healthcare professionals offer pre-test counseling themselves. We aimed to explore the impact of mainstream genetic testing on patients' experiences, turnaround times and adherence of non-genetic healthcare professionals to the mainstream genetic testing protocol. METHODS: Patients receiving pre-test counseling at the gynecology departments between April 2018 and April 2020 were eligible to participate in our intervention group. Patients receiving pre-test counseling at the genetics department between January 2017 and April 2020 were eligible to participate in our control group. We evaluated patients' experiences with questionnaires, consisting of questions regarding knowledge, satisfaction and psychosocial outcomes. Patients in the intervention group were sent two questionnaires: one after pre-test counseling and one after receiving their DNA test result. Patients in our control group were sent one questionnaire after receiving their test result. In addition, we collected data regarding turnaround times and adherence of non-genetic healthcare professionals to the mainstream genetic testing protocol. RESULTS: Participation was 79% in our intervention group (105 out of 133 patients) and 60% in our control group (91 out of 152 patients). Knowledge regarding genetics, decisional conflict, depression, anxiety, and distress were comparable in the two groups. In the intervention group, the risk of breast cancer in patients carrying a pathogenic germline variant was discussed less often (49% versus 74% in control group, p ≤ 0.05), and the mean score of regret about the decision to have genetic testing was higher than in the control group (mean 12.9 in the intervention group versus 9.7 in the control group, p ≤ 0.05), although below the clinically relevant threshold of 25. A consent form for the DNA test and a checklist to assess family history were present for ≥ 95% of patients in the intervention group. CONCLUSION: Mainstream genetic testing is an acceptable approach to meet the increase in genetic testing among women with epithelial ovarian cancer.

The impact of para-aortic lymph node irradiation on disease-free survival in patients with cervical cancer: A systematic review and meta-analysis.

Background: Patients with locally advanced cervical cancer without para-aortic lymph node metastases (PAO-LNM) at diagnosis who undergo concurrent chemoradiotherapy are at 4-11% risk of developing PAO-LNM during follow-up. Some studies suggest a beneficial influence of elective para-aortic radiotherapy (PAO-RT) on disease-free survival (DFS) in these patients. The aim of this study was to systematically review and meta-analyse literature on the impact of PAO-RT on DFS in cervical cancer patients. Methods: A systematic search of PubMed/MEDLINE and EMBASE databases was performed. The analysis included intervention studies that reported on DFS in patients with cervical cancer who received chemotherapy and pelvic radiotherapy with or without PAO-RT. From each included study, relevant study characteristics and outcome data including the hazard ratio (HR) adjusted for potential confounders were extracted. An overall pooled adjusted hazard ratio (aHR) for DFS after PAO-RT versus no PAO-RT was calculated using a random-effects model. Results: A total of 2,016 articles were evaluated. Eleven articles were included in the systematic review, of which 3 were appropriate for quantitative meta-analysis. Pooling of these 3 cohorts (including 1,113 patients) demonstrated a statistically significant association between PAO-RT and DFS (pooled aHR 0.87, 95% confidence interval: 0.79-0.97). No significant heterogeneity among reported aHRs was observed (I2 = 0.0%). Conclusions: This meta-analysis suggests a modest but significant beneficial impact of elective para-aortic radiotherapy on DFS in patients with locally advanced cervical cancer who undergo concurrent chemoradiotherapy. This finding based on non-randomized studies provides an imperative for further investigation in prospective controlled trials.

Feasibility of a drop-in γ-probe for radioguided sentinel lymph detection in early-stage cervical cancer.

BACKGROUND: Minimally invasive radioguided sentinel lymph node (SLN) procedures, increasingly performed with robot-assisted laparoscopy, can benefit from using a drop-in γ-probe instead of the conventional rigid laparoscopic γ-probe. We evaluated the safety and feasibility of a tethered drop-in γ-probe system for SLN detection in patients with early-stage cervical cancer. METHODS: Ten patients with FIGO stage IA - IB2 or IIA1 cervical cancer scheduled for robot-assisted laparoscopic SLN procedure were included. All patients underwent preoperative 240 MBq technetium-99m nanocolloid (99mTc) injection and SPECT/CT imaging. Intraoperatively the tethered drop-in γ-probe SENSEI® (Lightpoint Medical Ltd, Chesham, UK) was used for probe guided SLN detection, subsequently confirmed by the standard rigid laparoscopic γ-probe. Sentinel lymph node detection rates and anatomical SLN location were assessed. Surgeon questionnaires were used to assess usability. RESULTS: In all patients at least one SLN was successfully resected under guidance of the drop-in γ-probe (overall detection rate: 100%). Bilateral SLN detection rate with the drop-in γ-probe was 80%. Of the two patients with unilateral SLN detection only, one presented with an atypical SLN location at the aortic bifurcation that was detected only on SPECT/CT. The other patient had failed unilateral 99mTc uptake. Combined use of preoperative SPECT/CT and drop-in γ-probe resulted in a bilateral detection rate of 90%. Similar to the drop-in γ-probe, overall and bilateral SLN detection rate of the rigid γ-probe was 100% and 80%, respectively. No significant discrepancy existed between the count rate of the drop-in and rigid laparoscopic γ-probe (p = 0.69). In total 21 SLN's were detected with the drop-in γ-probes including all three tumor positive nodes. Because of wristed articulation of the robotic tissue grasper and possibility of autonomous probe control by the surgeon, maneuverability and control with the drop-in γ-probe were highly rated in surgeon questionnaires. No adverse events related to the intervention occurred. CONCLUSIONS: Sentinel lymph node detection with a drop-in γ-probe is safe and feasible in patients with early-stage cervical cancer. Use of the drop-in γ-probe enhances maneuverability and surgical autonomy during robot-assisted SLN detection. Trial registration Netherlands Trial Registry, NL9358. Registered 23 March 2021, https://www.trialregister.nl/trial/9358 .

Prognostic impact of waiting time between diagnosis and treatment in patients with cervical cancer: A nationwide population-based study.

OBJECTIVE: Prior research underlined the importance of timely oncological care as longer waiting times from diagnosis to treatment may result in poorer survival outcomes. The aim of this study was to determine the impact of waiting time from diagnosis to treatment on overall survival (OS) in patients with cervical cancer treated with curative intent. METHODS: Patients from a nationwide population-based cohort with newly diagnosed cervical cancer between 2010 and 2019 were studied. Patients who underwent surgery or (chemo)radiotherapy with curative intent were selected. Waiting time (i.e. interval between first pathologic confirmation and treatment) was modelled as continuous (i.e. linear per week), dichotomized (i.e. ≤8 versus >8 weeks), and polynomial (i.e. restricted cubic splines). The association with OS was examined using Cox regression analyses. RESULTS: Among 6895 patients with cervical cancer, 2755 treated with primary surgery and 1898 who received primary (chemo)radiotherapy were included. Mean waiting time was 8.5 (±4.2) weeks to surgery and 7.7 (±2.9) weeks to (chemo)radiotherapy. Adjusted for confounders, waiting time to surgery was not significantly associated with OS (continuous HR 0.97 [95%CI: 0.93-1.01], dichotomized HR 0.93 [95%CI: 0.68-1.27], polynomial HR not significant). Similarly, a longer waiting time to (chemo)radiotherapy was not significantly associated with poorer OS (continuous HR 0.97 [95%CI: 0.93-1.00], dichotomized HR 0.91 [95%CI: 0.75-1.09], polynomial HR not significant). CONCLUSIONS: This large population-based study demonstrates that a longer waiting time (of up to 12 weeks) from diagnosis to treatment in patients with cervical cancer treated with curatively intended surgery or (chemo)radiotherapy does not negatively impact survival.

Efficacy and Long-term Outcomes of Repeated Large Loop Excision of the Transformation Zone of the Cervix.

OBJECTIVE: To evaluate the efficacy and long-term outcome of repeat large loop excision of the transformation zone in women with residual or recurrent cervical intraepithelial neoplasia. METHODS: PALGA (the Dutch Pathology Registry), a database of deidentified cervical cytologic and histologic data, was used to examine women with cervical dysplasia who underwent two or more large loop excision of the transformation zone procedures between January 2005 and June 2015. We obtained cervical cytology and histology results. The main outcome was efficacy of repeated large loop excision of the transformation zone procedure in women with residual or recurrent cervical intraepithelial neoplasia. We also examined subsequent excisional procedures and hysterectomy. RESULTS: We identified 499 women who had undergone two or more large loop excision of the transformation zone procedures. After their second procedure, 60.7% of women had a normal first cervical cytologic sample. The mean duration of follow-up was 68 months (0-163 months). Additional cervical excisional procedures were performed in 33.7% of women. Overall, 1.2% of women developed cervical cancer during follow-up. Moreover, 19.0% of women eventually underwent hysterectomy. CONCLUSION: One third of the women who undergo two large loop excision of the transformation zone procedures require an additional excisional procedure or hysterectomy. Almost one fifth of these women eventually undergo hysterectomy.

Upstaging by para-aortic lymph node dissection in patients with locally advanced cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Accurate staging of para-aortic nodal status in cervical cancer is of great importance for individualizing treatment and impacting outcomes. Three-dimensional imaging (i.e. PET, CT, MRI) may miss para-aortic lymph node (PALN) metastases. The aim of this study was to systematically review and meta-analyze the proportion of upstaging by PALN dissection in patients with locally advanced cervical cancer without suspicious PALNs on imaging. METHODS: PubMed/MEDLINE and Embase were systematically searched. The analysis included diagnostic studies that reported on 3D imaging and pre-therapeutic surgical assessment of PALN status in patients with cervical cancer. An overall pooled upstaging rate was calculated using a random-effects model. RESULTS: The search identified 16 eligible studies including 18 cohorts with a total of 1530 patients. Pooling of 12 cohorts demonstrated an upstaging rate of 12% (95% confidence interval [CI] 10-15%) by PALN dissection after negative PET or PET-CT. Pooling of 6 cohorts demonstrated a pooled upstaging rate of 11% (95% CI: 8-16%) by PALN dissection after negative MRI or CT. No significant heterogeneity in upstaging proportions across cohorts was observed (I2 = 0% and 27%, respectively). In 7 cohorts including only patients with pelvic nodal metastases on imaging (but no suspicion of PALN involvement) a pooled upstaging rate by PALN dissection of 21% (95% CI: 17-26%) was found (I2 = 0%). CONCLUSIONS: This meta-analysis demonstrates that in case of no suspicious PALN on PET-CT or MRI, PALN dissection still identifies lymph node metastases in a considerable amount of patients with locally advanced cervical cancer and especially in those patients with confirmed pelvic nodal metastases.

Indocyanine green versus technetium-99m with blue dye for sentinel lymph node detection in early-stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: The fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early-stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached. AIMS: We aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium-99m (99m Tc) with blue dye. METHODS AND RESULTS: We searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99m Tc with blue dye in early-stage cervical cancer. The overall and bilateral detection rates were pooled with random-effects meta-analyses. From 118 studies retrieved seven studies (one cross-sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99m Tc with blue dye. Meta-analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99m Tc with blue dye; 90.3% (95%CI, 79.8-100.0%) with ICG versus 73.5% (95%CI, 66.4-80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3-28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI -0.8-27.3%). CONCLUSION: ICG appears to provide higher bilateral SLN detection rates compared to 99m Tc with blue dye in patients with early-stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, the quality of evidence is too low to provide strong recommendations and directly omit the combined approach of 99m Tc with blue dye.

Robot-assisted laparoscopic debulking surgery for recurrent adult granulosa cell tumors.

Despite an often early diagnosis and effective initial surgical management, one third of adult granulosa cell tumors (aGCTs) eventually, and often repeatedly, recurs. Debulking surgery remains the preferred treatment modality for recurrent aGCT, although the risk of intraoperative complications increases with repeated laparotomy. Minimally invasive surgery may limit the risk of complications. We aim to share our initial experience with robotic debulking surgery for recurrent aGCT. Clinical and surgical data of patients with recurrent aGCT who underwent robotic cytoreductive surgery over a three-year period at a tertiary referral center were retrospectively collected and analyzed. Between 2017 and 2020, three patients underwent robotic debulking surgery for recurrent aGCT at our institution. Complete cytoreduction was achieved in all patients. No intraoperative or postoperative complications were reported. This small pilot series at a single academic institution suggests that robot-assisted laparoscopy may be feasible and safe in selected patients with recurrent aGCT. A minimally invasive approach could reduce the complexity of successive surgeries for aGCT relapse.

The attributive value of comprehensive surgical staging in clinically early-stage epithelial ovarian carcinoma: A systematic review and meta-analysis.

BACKGROUND: Tumor positivity and upstaging rates from various surgical staging steps performed in clinically early-stage epithelial ovarian carcinoma (EOC) vary widely in literature. AIM: To quantify tumor positivity and upstaging rates for all staging surgery steps in EOC patients. Differences between subgroups based on their clinical and histological characteristics are explored. METHODS: A systematic search using synonyms of 'ovarian cancer', 'neoplasm staging', and 'neoplasm metastasis' was conducted in PubMed, Embase, and the Cochrane Library. Meta-analysis was performed on 23 included studies, comprising 5194 clinical stage I or II EOC patients who underwent comprehensive surgical staging. 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. 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.

Treatment of Cervical Intraepithelial Neoplasia: Patients Preferences for Surgery or Immunotherapy with Imiquimod.

Imiquimod has been studied as a noninvasive pharmacological treatment alternative to large loop excision of the transformation zone (LLETZ) for high-grade cervical intraepithelial neoplasia (CIN), to prevent long-term obstetric complications from surgical treatment. This study aims to investigate womens' preferences for treatment of high-grade CIN with imiquimod or LLETZ. A labeled discrete choice experiment was conducted among 100 women with abnormal cervical cytology in 5 hospitals in the Netherlands between March 2014 and December 2015. Participants were asked to choose between imiquimod treatment or standard surgical treatment in 9 separate scenarios, based on the following treatment characteristics: treatment success rate, rate of side effects, risk of premature birth in subsequent pregnancies, and risk of subfertility after treatment. The levels of these characteristics differed for the imiquimod alternatives. Women assigned a positive utility to LLETZ compared with imiquimod. When making a choice for imiquimod, women preferred a higher treatment success rate and a lower risk of premature birth, infertility and side effects. The choice for imiquimod treatment was also influenced by the intention of a future pregnancy. Subgroup analyses revealed that a lower efficacy regarding imiquimod might be more acceptable for women who desired a future pregnancy compared with women who did not desire a future pregnancy. Women with a future pregnancy wish may prefer treatment of high-grade CIN with imiquimod cream over LLETZ, if the risk of subfertility and premature birth is low.

Nomogram for suboptimal cytoreduction at primary surgery for advanced stage ovarian cancer.

AIM: Maximal cytoreduction to minimal residual tumor is the most important determinant of prognosis in patients with advanced stage epithelial ovarian cancer (EOC). Preoperative prediction of suboptimal cytoreduction, defined as residual tumor >1 cm, could guide treatment decisions and improve counseling. The objective of this study was to identify predictive computed tomographic (CT) scan and clinical parameters for suboptimal cytoreduction at primary cytoreductive surgery for advanced stage EOC and to generate a nomogram with the identified parameters, which would be easy to use in daily clinical practice. MATERIALS AND METHODS: Between October 2005 and December 2008, all patients with primary surgery for suspected advanced stage EOC at six participating teaching hospitals in the South Western part of the Netherlands entered the study protocol. To investigate independent predictors of suboptimal cytoreduction, a Cox proportional hazard model with backward stepwise elimination was utilized. RESULTS: One hundred and fifteen patients with FIGO stage III/IV EOC entered the study protocol. Optimal cytoreduction was achieved in 52 (45%) patients. A suboptimal cytoreduction was predicted by preoperative blood platelet count (p=0.1990; odds ratio (OR)=1.002), diffuse peritoneal thickening (DPT) (p=0.0074; OR=3.021), and presence of ascites on at least two thirds of CT scan slices (p=0.0385; OR=2.294) with a for-optimism corrected c-statistic of 0.67. CONCLUSION: Suboptimal cytoreduction was predicted by preoperative platelet count, DPT and presence of ascites. The generated nomogram can, after external validation, be used to estimate surgical outcome and to identify those patients, who might benefit from alternative treatment approaches.

Prediction of residual disease after primary cytoreductive surgery for advanced-stage ovarian cancer: accuracy of clinical judgment.

OBJECTIVES: Treatment of patients with an advanced-stage epithelial ovarian cancer (EOC) is based on cytoreductive surgery and platinum-based chemotherapy. Amount of residual disease after primary cytoreductive surgery is an important prognostic factor. The objectives of the present study were to evaluate the accuracy and reproducibility of preoperative clinical judgment of residual disease after primary cytoreductive surgery and to compare the predictive performance of the offhand assessment to the predictive performance of prediction models. MATERIALS AND METHODS: Fifteen observers (5 gynecologic oncologists, 5 gynecologists, and 5 senior residents) were offered preoperative data of 20 patients with advanced-stage EOC who underwent primary cytoreductive surgery. The observers were asked to predict residual disease after cytoreductive surgery (1 cm). Their estimation was compared with the performance of 2 prediction models. RESULTS: Overall, suboptimal cytoreduction was predicted with a sensitivity of 50% and a specificity of 56%. The intraclass correlation coefficient was 0.27. chi(2) Test showed no significant difference in prediction of suboptimal cytoreduction between the different subgroups and prediction models. CONCLUSIONS: Clinical judgment of residual disease after primary cytoreductive surgery in patients with advanced-stage EOC shows limited accuracy. Given the poor interobserver reproducibility, prediction models could attribute to uniform treatment decisions and improve counseling.