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Tumor cells release fragments of their DNA into the circulation, so called cell-free tumor DNA (ctDNA), allowing for analysis of tumor DNA in a simple blood test, that is, liquid biopsy. Cervical cancer is one of the most common malignancies among women worldwide and high-risk human papillomavirus (HR-HPV) is the cause of the majority of cases. HR-HPV integrates into the host genome and is often present in multiple copies per cell and should thus also be released as ctDNA. Such ctHPV DNA is therefore a possible biomarker in cervical cancer. In this review, we first give a background on ctDNA in general and then a comprehensive review of studies on ctHPV DNA in cervical cancer and pre-malignant lesions that may develop in cervical cancer. Furthermore, studies on ctHPV DNA in other HPV related malignancies (eg, head-and-neck and anogenital cancers) are briefly reviewed. We conclude that detection of ctHPV DNA in plasma from patients with cervical cancer is feasible, although optimized protocols and ultra-sensitive techniques are required for sufficient sensitivity. Results from retrospective studies in both cervical cancer and other HPV-related malignancies suggests that ctHPV DNA is a promising prognostic biomarker, for example, for detecting relapses early. This paves the way for larger, preferably prospective studies investigating the clinical value of ctHPV DNA as a biomarker in cervical cancer. However, there are conflicting results whether ctHPV DNA can be found in blood from patients with pre-malignant lesions and further studies are needed to fully elucidate this question.

Tumor cells release fragments of their DNA into the circulation, so called cell-free tumor DNA (ctDNA) or liquid biopsy. Here, we analyze if cell-free human papillomavirus DNA (ctHPV DNA) is detectable before, during and after treatment, in patients with cervical cancer or pre-malignant lesions that may develop into cervical cancer, and whether ctHPV DNA levels were correlated to patient or tumor characteristics and outcome. Furthermore, total cell-free DNA load is studied using cfAlbumin DNA as a surrogate marker.18 patients with locally advanced CC (LACC), 15 patients with early stage CC (ESCC) and 21 patients with pre-malignant lesions, all with verified HPV16, 18 or 45-positive lesions, were included. Pre- during- and post-treatment plasma were tested for HPV16, 1845 and total cfDNA load using droplet digital PCR.ctHPV DNA was found in 94.4% and 26.7% of pre-treatment plasma of patients with LACC and ESCC respectively, while all samples from patients with pre-malignant lesions were negative. Higher levels of ctHPV DNA were correlated to higher FIGO2018 stage. Patients with LACC and persistent ctHPV DNA at end-of-treatment had significantly worse progression-free survival (PFS) than patients who had cleared the ctHPV DNA (p = 0.007). Patients with total ctDNA-levels above median in pre-treatment plasma had a worse PFS (p = 0.026), compared to patients with total ctDNA-levels below median.ctHPV DNA is a promising prognostic biomarker in locally advanced cervical cancer that should be studied further for clinical use.

To examine whether objective bladder function after robot-assisted radical hysterectomy (RRH) for early-stage cervical cancer is correlated with subjective patient-reported outcomes and quality of life during the first year after RRH.Prospective observational study.Karolinska University Hospital, Sweden.Women with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA2-IB1) between July 2017 and May 2019 were assessed for eligibility.RRH.Subjective bladder function was evaluated with the Female Lower Urinary Tract Symptoms and Urinary Incontinence Quality of Life modules of the International Consultation on Incontinence Questionnaire. Objective urinary function was characterized with urodynamic tests, and the nerves ablated at RRH were quantified by using immunohistochemical staining of biopsies from the resected paracervix, vesicouterine, and sacrouterine ligaments. Twenty-seven women were included for analysis at baseline, 2 weeks, 3 months, and 12 months after surgery. RRH caused hypotonia of the urinary bladder (p.05). Patient-reported outcomes of voiding and filling dysfunction were most significant 2 weeks after surgery (p.05) but for most of the women, bladder function recovered within 3 months. No correlations were found with either subjective or objective urinary function and the number of ablated nerves.For most women, objective and subjective urinary bladder dysfunction recovered within 3 months after RRH. The absence of correlation between functional outcomes and ablated autonomous nerves suggests that other underlying causes play a significant role. Early detection of bladder overextension after RRH is paramount, and the role of postoperative bladder catheterization needs further investigation.

OBJECTIVE: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection.METHODS: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+.RESULTS: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm-had a very low risk of pN+ (2.4%, 95% CI, 1.7-3.3%).CONCLUSION: Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.

Purpose Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Methods Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Results Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. Conclusion The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

Objectives Women with a previous trachelectomy have an increased risk of premature delivery and second trimester miscarriage. In this study we aim to evaluate factors and regimes possibly affecting the risk for prematurity following fertility sparing robotic radical trachelectomy (RRT) in cervical cancer. Methods A retrospective study of the reproductive outcome following RRT with a cervical cerclage performed at one of four academic centers between 2007 and 2019. Factors possibly related to premature delivery, such as postoperative non-pregnant cervical length, previous vaginal deliveries, preservation of the uterine arteries, and the use of a second trimester oral metronidazole/no sexual intercourse regime, were assessed. Results 109 women remained for analyses after excluding recurrences before pregnancy (n = 8), secondary hysterectomy (n = 2), and women with less than six months follow up (n = 10). 74 pregnancies occurred in 52/71 women attempting to conceive, 56 of which developed past the first trimester. Two of 22 women (9%) who were prescribed an oral metronidazole regime (400 mg × 2 from gestational week 15 + 0 to 21 + 6 and abstaining from sexual intercourse for the duration of the pregnancy) had a premature delivery, compared with 13/31 (42%) where the regime was not applied (p = 0.009). The association remained after regression analyses including possible contributing factors as of above, none of which associated with prematurity at regression analyses (p = 0.001). Conclusions The observed four-fold reduction in premature delivery indicates that an oral metronidazole/no sexual intercourse regime may reduce second trimester miscarriage and premature deliveries following an RRT. No association was observed for other investigated factors.

ObjectiveTo achieve the full potential of sentinel lymph node (SLN) detection in endometrial cancer, both presumed low- and high-risk groups should be included. Perioperative resource use and complications should be minimized. Knowledge on distribution and common anatomical sites for metastatic SLNs may contribute to optimizing the concept while maintaining sensitivity. Proceeding from previous studies, simplified algorithms based on histology and lymphatic anatomy are proposed.MethodsData on mapping rates and locations of pelvic SLNs (metastatic and non-metastatic) from two previous prospective SLN studies in women with endometrial cancer were retrieved. Cervically injected indocyanine green was used as a tracer and an ipsilateral re-injection was performed in case of non-display of the upper and/or lower paracervical pathways. A systematic surgical algorithm was followed with clearly defined SLNs depicted on an anatomical chart. In high-risk endometrial cancer patients, removal of SLNs was followed by a pelvic and para-aortic lymphadenectomy.Results423 study records were analyzed. The bilateral mapping rates of the upper and lower paracervical pathways were 88.9% and 39.7%, respectively. 72% of all SLNs were typically positioned along the upper paracervical pathway (interiliac and/or proximal obturator fossa) and 71 of 75 (94.6%) of pelvic node positive women had at least one metastatic SLN at either of these positions. Women with grade 1–2 endometroid cancers (n=275) had no isolated metastases along the lower paracervical pathway compared with two women with high-risk histologies (n=148).ConclusionSLNs along the upper paracervical pathway should be identified in all endometrial cancer histological subtypes; removal of nodes at defined typical positions along the upper paracervical pathway may replace a site-specific lymphadenectomy in case of non-mapping despite tracer re-injection. Detection of SLNs along the lower paracervical pathway can be restricted to high-risk histologies and a full pre-sacral lymphadenectomy should be performed in case of non-display.

Introduction/Background* The impact of lymph node (LN) micrometastases (MIC) in cervical cancer patients remains a controversial topic given their low incidence and good prognosis of patients managed by primary surgery. We aim to evaluate the prognostic significance of MIC and isolated tumour cells (ITC) in a large cohort of patients from the SCCAN retrospetive study (Surveillance in Cervical CANcer). SCCAN study analysed data from more than 4300 patients with early stage cervical cancer treated by primary surgery at 20 large tertiary institutions from Europe, North America, South America and Australia. Methodology In this SCCAN sub-study, we included patients with early stage cervical cancer (T1a1 LVSI+ – T2b) treated between 2007 and 2016 with at least 1-year follow-up data availability, who underwent primary surgery including sentinel lymph node (SLN) biopsy and in whom SLNs were processed by pathological ultrastaging protocol. Result(s)* Out of 969 included patients with at least 1 SLN detected, 174 (18%) had positive LN (table 1). Maximal tumour diameter >2cm, positive LVSI, grade ≥ 2, uncommon histological type (neuroendocrine, sarcoma, etc.) and macrometstasis (MAC) or MIC in LN were factors associated with significantly decreased five-years disease free survival (DFS) (table 2). MAC, MIC or ITC was the largest LN metastasis in 84 (9%), 59 (6%) and 31 (3%) cases respectively. Adjuvant (chemo)radiation was administred in 89%, 85% and 58% of patients with MAC, MIC and ITC. DFS reached 75%, 73% and 83% in patients with MAC, MIC and ITC compared with 90% in the N0 patients. Patients with MAC and MIC had significantly decreased DFS than those with N0 disease (HR=2.36 and 2.55). Conclusion* Early-stage cervical cancer patients with MIC in pelvic LN have significantly decreased DFS. Their management should follow the same principles as in patients with MAC.

Introduction/Background* Up to 26% of early-stage cervical cancer patients relapse after primary surgical treatment. However, little is known about the factors affecting prognosis following disease recurrence. Hence, the aim of this study was to evaluate post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors. Methodology Data from 528 early-stage cervical cancer patients who relapsed after primary surgical treatment performed between 2007 and 2016 were obtained from the SCCAN study (Surveillance in Cervical CANcer). Parameters related both to primary disease and recurrence diagnosis were combined to develop a multivariable Cox proportional hazards model predicting PR-DSS. Result(s)* Five-year PR-DSS reached 39.1% (95% confidence interval: 22.7% – 44.5%) with median disease-free survival between primary surgery and recurrence diagnosis (DFI1) of 1.5 years and median survival after recurrence of 2.5 years. Six variables significant in multivariable analysis were included in the PR-DSS prognostic model; two related to the primary disease characteristics: maximal diameter of the tumour and lymphovascular space invasion; and four related to the recurrence diagnosis: DFI1, age, presence of symptoms, and recurrence localization (table 1). C-statistics of the final model after 10-fold internal validation equalled 0.701 (95% CI: 0.675 – 0.727). Five risk groups significantly differing in prognosis were identified, with 5-year DSS after recurrence of 85.6%, 62.0%, 46.7, 19.7%, and 0% in the highest risk group (figure 1). Conclusion* We have developed the first robust model of disease-specific survival after recurrence stratifying relapsing cervical cancer patients according to their risk profile using six traditional prognostic markers. The strongest factor related to the length of post-recurrence survival was the largest size of the primary tumour, followed by the presence of symptoms at the time of diagnosis, which remained significant even after correction for lead-time bias.

Introduction/Background* Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust and comprehensive model allowing for individualised surveillance strategy based on risk profile of early-stage cervical cancer patients that were referred for surgical treatment with curative intent. Methodology The data of 4,343 cervical cancer patients with pathologically confirmed early-stage cervical cancer treated between 2007 and 2016 were obtained from SCANN consortium centres of excellence (Surveillance in Cervical CANcer). Only patients with complete key predictor variables and a minimum of one-year follow-up data availability were included. Based on the prognostic markers, a multivariable Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. A risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated by conditional survival analysis. Result(s)* Five variables significant in multivariable analysis of recurrence risk were included in the prognostic model: maximal pathologic tumour diameter, tumour histotype, tumour grade, the number of positive pelvic lymph nodes, and lymphovascular space invasion (table 1). The model was ten-fold internally cross-validated with the average AUC of 0.732. Five risk groups significantly differing in prognosis were identified: with five-year DFS of 97.5%, 94.7%, 85.2%, and 63.3% in consecutive increasing risk groups, while two-year DFS in the highest risk group equalled 15.4%. Based on ARRM, the annual recurrence risk in the lowest risk group was below 1% in the first year of follow-up and declined below 1% at years three, four, and >5 in the three medium-risk groups (figure 1). The proportion of pelvic recurrences declined in groups with the growing risk. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two, and 78% by year five. Conclusion* ARRM represents a powerful tool for tailoring the surveillance strategy in early-stage cervical cancer patients based on the patient´s risk status and respective annual recurrence risk. It can easily be utilised in routine clinical settings internationally.

Complete macroscopic resection without any residual tumour after completion of surgery is a strong prognostic factor in advanced epithelial ovarian cancer (EOC). It has previously been reported that surgery performed later in the week is associated with failure to achieve complete macroscopic resection. Our objective was to examine if weekday of surgery influences oncologic outcome.This population-based observational study included 100% of all women diagnosed with advanced-stage invasive epithelial ovarian cancer between 2009-2011 and 2014-2016 in the Stockholm/Gotland County of Sweden. The association between weekday of surgery and survival was analysed with proportional hazards regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for predefined confounders.Out of 1066 identified women, 524 with advanced stage EOC treated with surgery were included in the final analysis. Surgery performed Wednesday to Thursday was associated with an increased hazard of death (HR 1.28, 95% CI 1.04-1.58,The increased mortality associated with surgery that is performed later in the week suggests that surgery for advanced ovarian cancer is best conducted early in the week.

BackgroundRadical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy.Primary ObjectiveTo compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy.Study HypothesisWe hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach.Study DesignThis is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data.Inclusion CriteriaPatients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both).Exclusion CriteriaPrior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach.Primary EndpointThe primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy.Sample SizeAn estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.

IntroductionSentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance.MethodsA Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability.ResultsSeventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; PConclusionSpecific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

The treatment of gynecologic malignancies may impact fertility, and this is critical given that 15–20% of these neoplasms occur in women under 40 years of age. In addition, as a result of professional and personal goals, a considerable number of women are postponing childbearing until 30–40

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS.METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS.RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%.CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Radical trachelectomy is the ‘cornerstone’ of fertility-sparing surgery in patients with early-stage cervical cancer wishing to preserve fertility. Growing evidence has demonstrated the oncologic safety and subsequent favorable pregnancy outcomes in well-selected cases. In the absence of prospective trials, the decision on the appropriate surgical approach (vaginal, open, or minimally invasive surgery) should be based on local resources and surgeons’ preferences. Radical trachelectomy has the potential to preserve fertility in a large proportion of women with early-stage cervical cancer. However, prematurity and premature rupture of membranes are common obstetric complications after radical trachelectomy for cervical cancer. A multidisciplinary approach is crucial to optimize the balance between oncologic and obstetric outcomes. The purpose of this review is to provide an updated overview of the technical, oncologic, and obstetric aspects of radical trachelectomy.

Objective. To examine the patterns of recurrence and how these patterns are associated with survival in vulvar squamous cell carcinoma. We also explored the survival impact of surgical groin staging (SGS). Methods. Nationwide population-based study including women diagnosed with vulvar squamous cell carcinoma between 2012 and 2015 and registered in the Swedish Quality Registry for Gynecologic Cancer. Cumulative incidence rates (CIR), recurrence-free (RFS) and overall survival (OS) were calculated by Kaplan Meier estimates. The impact of SGS on RFS and OS was analyzed by proportional hazards models. Results. 489 eligible women were included. Median follow-up time was 64 months. The overall recurrence rate was 22.3%. Site of recurrence: local in 61.0%, groin in 30.0%, distant in 9.0%. The CIR for local recurrences increased with time (5.9% at 2-years, 14.7% at 5-years) while the rate of groin and distant recurrences was nearly steady (5.5% to 6.3% and 1.5% to 1.7%, respectively). Median 2-year and 4-year OS post-recurrence was 57.8% and 37.4% for local, 17.2%, 10.3% for groin and 0% for distant recurrences, respectively. SGS was omitted in 23.7% of surgically treated women with FIGO stages IB-II and significantly associated with worse RFS (Hazard ratio, HR, 1.9; 95%CI, 1.0-3.5; p = 0.04) and OS (HR 2.0; 95%CI, 1.1-3.8; p = 0.04) after adjustment for age, FIGO stage, tumor size, resection margins and performance status. Conclusion. The cumulative incidence of isolated vulvar recurrence was low but for those affected the prognosis was poor. Surgical groin staging is a crucial part of primary treatment and should not be omitted. (c) 2021 Published by Elsevier Inc. Funding Agencies|Swedish Society for Gynecologic Cancer

Introduction/Background The aim of this study was to evaluate the impact of institutional surgical experience on recurrence following robotic radical hysterectomy (RRH) for early stage cervical cancer. Methodology All women in Sweden who underwent an RRH for stage IA2-IB1 cervical cancer at tertiary referral centers from its implementation in December 2005 until June 2017 were identified using a Swedish nationwide register and local hospital registers. Registry data was controlled by a chart review on all women. Recurrence rates and pattern of recurrence was compared between early and late (≤50 vs >50 procedures) institutional series. Results 635 women were included. Regression analysis identified a lower risk of recurrence with increased experience but without a clear cut off level. Among the 489 women who did not receive adjuvant radio chemotherapy (RC-T), the rate of recurrence was 3.6% in the experienced cohort (>50 procedures) compared to 9.3% in the introductory cohort (p Conclusion In conclusion, the rate of recurrence following RRH for early stage cervical cancer decreased with increased institutional surgical experience, in tumors Disclosures Jan Persson, Henrik Falconer and Celine Lonnerfors have received honoraria for lectures and proctoring in robotic surgery, all outside the presented research. The other authors have no conflicts of interest.

Objectives: We sought to evaluate pregnancy-related outcomes in women who elected to undergo uterine-artery preserving robotic-assisted radical trachelectomy (RRT) for fertility-sparing treatment of early stage cervical cancer. Methods: This is a retrospective, multi-institutional, international study of patients who underwent attempted uterine artery-preserving RRT for primary treatment of FIGO 2009 clinical stage IA1, IA2 and stage IB1 cervical cancer. All consecutive patients undergoing surgery at 5 academic centers in Sweden, the US, England, and South Korea between December 2007 and September 2019 were included. RRT was performed as a fertility-sparing treatment for stage IA2 and IB1 disease as well as for stage IA1 disease with lymphovascular space invasion, multifocal disease, adenosquamous histology, or a cone biopsy with positive margins. Demographic and clinical data were collected via chart review. We used Studentas T-test or Mann Whitney to compare continuous variables and Pearsonas Chis-test for categorical variables. Variables were entered into a Microsoft Excel database and analyzed using SPSS version 12.0 statistical software (SPSS, Chicago, IL, USA). Results: Of 194 patients taken to the OR for attempted RRT, 185 underwent RRT, and 176 had bilateral preservation of the uterine arteries. Mean age was 31 years (range 18 to 51). Histologic classifications included squamous cell (n=111), adenocarcinoma (n=65), and adenosquamous (n=6). A total of 9 patients had aborted RRT for intraoperative finding of a positive node or margin. A total of 8 patients underwent completion hysterectomy based on final pathology. A total of 15 patients received adjuvant treatment. Of the 155 patients who had neither hysterectomy nor adjuvant therapy, 91 (58.7%) attempted pregnancy and 69 (75.8%) achieved pregnancy. Of a total of 100 pregnancies, there were 70 live births (70%), 21 first trimester losses (21%), 5 second trimester losses (5%), and 4 (4%) patients are currently pregnant. Of the live births, 6 (8.6%) were delivered very preterm before 32 weeks gestation and 52 (74.3%) were delivered via planned cesarean section after 36 weeks. Compromise of at least one uterine artery significantly increased the rate of delivery before 36 weeks (17% vs 2%, p=0.02). The median follow-up was 51 months. Conclusions: Preservation of the uterine arteries bilaterally may lead to improved obstetric outcomes. This is the largest series reporting outcomes of uterine-artery preserving RRT to date and provides important data for counseling patients considering fertility-sparing treatment of early cervical cancer.

The aim of this study was to evaluate the impact of institutional surgical experience on recurrence following robotic radical hysterectomy (RRH) for early stage cervical cancer. All women in Sweden who underwent an RRH for stage IA2-IB1 cervical cancer at tertiary referral centers from its implementation in December 2005 until June 2017 were identified using a Swedish nationwide register and local hospital registers. Registry data were controlled by a chart review of all women. Recurrence rates and patterns of recurrence were compared between early and late (&le, 50 vs. &gt, 50 procedures) institutional series. Six hundred and thirty-five women were included. Regression analysis identified a lower risk of recurrence with increased experience but without a clear cut off level. Among the 489 women who did not receive adjuvant radio chemotherapy (RC-T), the rate of recurrence was 3.6% in the experienced cohort (&gt, 50 procedures) compared to 9.3% in the introductory cohort (p &lt, 0.05). This was also seen in tumors &lt, 2 cm regardless of RC-T (p &lt, 0.05), whereas no difference in recurrence was seen when analyzing all women receiving RC-T. In conclusion, the rate of recurrence following RRH for early stage cervical cancer decreased with increased institutional surgical experience, in tumors &lt, 2 cm and in women who did not receive adjuvant RC-T.

Aim Salpingectomy is associated with a lower risk for ovarian cancer, suggesting that the fallopian tubes constitute the origin of the disease. It is unclear whether the observed effect is mediated by pelvic inflammatory disease (PID); a major indication for salpingectomy and implicated in the aetiology of ovarian cancer. Methods In this population-based cohort study, we used nationwide registry-based data on women exposed for PID with and without subsequent salpingectomy (n = 97,912) compared with the unexposed population (n = 5,429,174) between 1973 and 2010. The effect of hormone treatment was considered in a subanalysis. Results Of the exposed women, 9538 women underwent salpingectomy during the study period. There was a significant association between PID and ovarian cancer (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.31–1.59), whereas an inverse association was observed for exposed women with subsequent salpingectomy (HR 0.55, 95% CI 0.36–0.83). Salpingectomy performed on other indications (n = 24,895) was associated with a lower incidence of ovarian cancer (HR 0.72, 95% CI 0.56–0.93). No effect modification was observed for the use of oral contraceptives or hormonal replacement therapy. Conclusion Salpingectomy is associated with a lower incidence of ovarian cancer regardless of indication.

Objective Ultra-radical surgery to achieve complete resection in advanced epithelial ovarian cancer (EOC) has been widely accepted without strong supporting data. Our objective was to assess overall survival after a structured shift to an ultra-radical upfront surgical treatment algorithm and to investigate changes in the distribution of primary treatments after this shift. Patients and methods In this population-based cohort study, all women with suspected EOC in the Stockholm-Gotland region of Sweden reported to the Swedish Quality Registry for Gynecologic Cancer (SQRGC) and National Cancer Registry (NCR) were selected in two 3-year cohorts, based on year of diagnosis (before (cohort1) or after (cohort 2) change in surgical treatment algorithm) and followed for at least three years. 5-year overall survival (OS) in non-surgically and surgically treated women was analyzed. Moreover, proportional distribution of primary treatment was evaluated. Results 752 women were included in the final analysis (n = 364 and 388 in cohort 1 and 2 respectively) with a median follow-up of 29 and 27 months. The complete resection rate increased from 37 to 67% (p ≤ 0.001) as well as proportion non-surgically treated women, 24 to 33%. No improvement in OS was observed in non-surgically (HR 0.76 (95% CI, 0.58–1.01); p = 0.06) or surgically treated (HR 0.94 (95% CI, 0.75–1.18); p = 0.59) women, even when complete resection was achieved (HR 1.31 (95% CI, 0.89–1.92); p = 0.17). Conclusion A shift to ultra-radical upfront surgery in EOC did not improve survival despite a significant increase in complete resection rate. Identifying the limitations of surgical treatment remains a challenge.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005–2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20–42) years for open surgery vs 31 (18–45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0–31) mm for open surgery and 12 (0.8–40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20–16.70) years for open surgery and 3.1 years (0.02–11.10) years for minimally invasive surgery (P

Tubal ligation results in less advanced stages and lower risk of metastatic spread at diagnosis of endometrial cancer (EC) but the primary preventive effect of the procedure is unclear. In a Swedish nationwide population-based cohort study, we crosslinked registry data for tubal ligation, EC, and death for Swedish women between 1973 and 2010. All women were followed until EC, emigration, hysterectomy for non-cancerous reasons, death, or end of follow-up. Primary outcome was incidence of EC and secondary outcome overall survival. We calculated adjusted incidence rates (IR) per 100,000 person-years and hazard ratios (HR) using Cox regression models. A total of 35,711 cases of EC were identified among 5,385,186 women. The IR of EC among exposed was 17.7 (95% CI 15.7-19.9) versus 29.0 (95% CI 28.7-29.3) among unexposed (per 100,000 women years). Exposed individuals had significantly reduced risk of EC (HR 0.73, 95% CI 0.65-0.83). The mortality rate among women with EC was 72% lower in exposed compared to unexposed (IR 1,441; 95% CI 1,089-1,907 and IR 5,136; 95% CI 5,065-5,209, respectively) which following adjustment corresponded to a HR of 0.71 (95% CI 0.49-1.03). Tubal ligation was associated with lower risk of EC as well as mortality rates in women with EC. Elective tubal ligation may be adopted in future cancer preventive strategies but must be balanced against the irreversibility of the procedure, which preclude further unassisted reproduction.

The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin.Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models.Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P0.001), moderate (RR 1.90, P0.047) and poor differentiation (RR 2.20, P0.009), neoadjuvant chemotherapy (RR1.33, P0.022), residual tumor (RR 2.65, P0.001) and platinum single (2.34, P0.001) compared to platinum combination chemotherapy.Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

Fistula formation between bowel and blood-vessel is a very rare complication after intraabdominal surgery. We report a case of iliaco-enteric fistula following robot-assisted surgical staging of endometrial cancer. A 71-year-old woman subjected to comprehensive endometrial cancer staging presented with hematochezia 35 days postoperatively. A retroperitoneal right-sided abscess and an iliaco-enteric fistula was confirmed upon imaging. The patient received endovascular repair of the aneurysm in her right common iliac artery and the segments of the small bowel containing the fistula were resected via laparotomy. If a patient presents with new onset postoperative hematochezia after pelvic and/or paraaortic lymphadenectomy, fistulation between bowel and the major abdominal blood vessels should be part of the differential diagnoses.

Introduction/Background Radical cytoreductive surgery is the most important prognostic factor for survival in women with advanced epithelial ovarian cancer (EOC). Extra-pelvic procedures, including bowel resections, are often necessary to achieve complete tumor resection. Anastomotic leakage (AL) is a severe postoperative complication with risk of perioperative death and delay in time to start of adjuvant chemotherapy. The objective of this study was to evaluate AL rates in relation to surgical specialty and complexity score. Methodology Consecutive women with advanced EOC who underwent bowel resection as part of cytoreductive surgery at Karolinska University Hospital between 2004–2011 and 2014–2016 were identified in hospital data bases. Descriptive statistics was performed. Results Ninety-three and 101 women were analyzed in the early (2004–2011) and late (2014–2016) cohorts respectively. Demographic data was similar between groups. Bowel surgery performed by colorectal surgeons decreased from 89% to 20% (p Conclusion Despite a significant increase of bowel resections performed by gynecologic oncologists, upfront surgery and SCS, there was no increase in AL rate. Bowel surgery can safely be performed by trained gynecological oncologists. Disclosure Nothing to disclose.

Objectives To compare disease-free survival (DFS) between patients who underwent open (ORT) versus minimally invasive (MIS) radical trachelectomy (RT) [laparoscopic (LRT) or robotic (RRT)]. Methods Eligibility criteria included 1) RT and pelvic lymphadenectomy with/without sentinel lymph node mapping, 2) 1/2005 to 12/2017 3) squamous, adenocarcinoma, or adenosquamous histology, 4) stage IA2-IB1, 5) tumors ≤2 cm, 6) 15 or more cases per center. Results A total of 698 patients [open (n=388) vs. MIS (310)] were included. The median follow-up time was 40.9 months (range, 1–179.1) [MIS 38.6 (range, Conclusions Surgical approach in radical trachelectomy for low-risk cervical cancer was not associated with differences in recurrence rates or survival. MIS had worse perioperative outcomes.

INTRODUCTION Surgery by open radical hysterectomy for cervical cancer is associated with sexual dysfunction as well as lymphedema and bladder problems. Our aim was to assess the impact of robot-assisted laparoscopic radical hysterectomy (RRH) with pelvic lymphadenectomy for early-stage cervical cancer on sexual, bowel, bladder, and lymphatic function and to measure ovarian function after RRH. MATERIAL AND METHODS Twenty-six women with early-stage cervical cancer during 2011-2013 were investigated before and 1 year after RRH using a validated questionnaire measuring psychological well-being and sexual, bowel, bladder, and lymphatic function. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex-hormone-binding globulin (SHBG), estradiol, total testosterone, androstenedione, and anti-Mullerian hormone (AMH) were analyzed at baseline and 1 year after treatment. RESULTS Anxiety and depression increased in 17/26 (62%) and 16/26 (65%) of the women respectively. Sexual distress symptoms reported 1 year after RRH were numbness of the labia (P = 0.04) and deep pain during intercourse (P = 0.02). Twelve of 26 (46%) had lymphedema, and 10/26 (35%) had bladder problems 1 year after surgery. Levels of FSH and LH were significantly increased (P

Study aims To prospectively assess the diagnostic accuracy of a pelvic sentinel lymph node (SLN) algorithm in high-risk endometrial cancer (HREC). Patients and methods Consecutive women with presumed FIGO stage I-II HREC underwent robotic surgery at two academic centres by five accredited surgeons. An anatomically based algorithm was adhered to, following cervical injection of indocyanine green (ICG), with reinjection of tracer in case of non-display of predefined lymphatic pathways. After removal of SLNs, a pelvic and infrarenal para-aortic lymphadenectomy was performed. Primary end-point was sensitivity of the SLN-ICG algorithm. Secondary end-points were sensitivity of the overall SLN algorithm (including macroscopically suspect nodes as SLNs), SLN mapping rates and morbidity of the SLN procedure. Results Two hundred fifty-seven women were analysed; 54 had pelvic lymph node metastases (LNMs), and 52 of those were correctly identified by the SLN-ICG algorithm. In two women (one with false-negative ICG-SLNs and one non-mapped woman), the pelvic LNMs were identified by the overall SLN algorithm. The SLN-ICG algorithm had a sensitivity of 98% (95% confidence interval [CI] 89–100) and a negative predictive value of 99.5% (95% CI 97–100). The sensitivity of the overall SLN algorithm was 100% (95% CI 92–100) and the negative predictive value was 100% (95% CI 98–100). The bilateral mapping rate was 95%. Two women (1%) had isolated para-aortic metastases. No adverse events occurred during the SLN procedure. Conclusion With a complete sensitivity to detect pelvic LNMs, the described pelvic SLN algorithm can, in the hands of experienced surgeons, exclude overall nodal involvement in 99% and thereby safely replace a full lymphadenectomy in HREC.

BackgroundRadical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.Primary ObjectiveTo investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.Study HypothesisRobot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.Trial DesignProspective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.Major Inclusion/Exclusion CriteriaWomen over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.Primary EndpointRecurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.Sample SizeThe clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1−β) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.Estimated Dates for Completing Accrual and Presenting ResultsTrial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.Trial RegistrationThe trial is registered at ClinicalTrials.gov (NCT03719547).

Hysterectomy on benign indications is associated with an increased risk for adverse health effects. However, little is known about the association between hysterectomy and subsequent cancer occurrence later in life. The purpose of this study was to assess the effect of hysterectomy on the incidence of cancer. In this population-based cohort study, we used data on 111,595 hysterectomized and 537,9843 nonhysterectomized women from nationwide Swedish Health Care registers including the Inpatient Register, the Cancer Register and the Cause of Death Register between 1973 and 2009. Hysterectomy with or without concomitant bilateral salpingo-ophorectomy (BSO) performed on benign indications was considered as exposure and incidence of primary cancers was used as outcome measure. Rare primary cancers (

Minimally invasive surgery has been widely adopted in gynaecologic oncology with a significant surge the past decade associated with the introduction of robot-assisted surgery. Up until 2018, virtually all testimonials of minimally invasive surgery for cervical cancer indicated equal oncologic outcomes compared to laparotomy. The unexpected results from the only randomised controlled trial (Ramirez PT et al, N Engl J Med, 2018;379:1895-1904) seriously challenge the use of minimally invasive surgery for cervical cancer.

The health-related quality of life (HRQoL) outcomes after comprehensive surgical staging including infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer (EC) are unknown. Our aim was to investigate the long-term HRQoL between robot-assisted laparoscopic surgery (RALS) and laparotomy (LT).A total of 120 women with high-risk stage I-II EC were randomised to RALS or LT for hysterectomy, bilateral salpingoophorectomy, pelvic and infrarenal paraaortic lymphadenectomy in the previously reported Robot-Assisted Surgery for High-Risk Endometrial Cancer trial. The HRQoL was measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-30) and its supplementary questionnaire module for endometrial cancer (QLQ-EN24) questionnaire. Women were assessed before and 12 months after surgery. In addition, the EuroQol Eq5D non-disease specific questionnaire was used for descriptive analysis.There was no difference in the functional scales (including global health status) in the intention to treat analysis, though LT conferred a small clinically important difference (CID) over RALS in 'cognitive functioning' albeit not statistically significant -6 (95% CI-14 to 0, p = .06). LT conferred a significantly better outcome for the 'nausea and vomiting' item though it did not reach a CID, 4 (95% CI 1 to 7, p = .01). In the EORTC-QLQ/QLQ-EN24, no significant differences were observed. Eq5D-3L questionnaire demonstrated a higher proportion of women reporting any extent of mobility impairment 12 months after surgery in the LT arm (p = .03).Overall, laparotomy and robot-assisted surgery conferred similar HRQoL 12 months after comprehensive staging for high-risk EC.

Background and ObjectivesIn the Robot Assisted Surgery for High Risk Endometrial Cancer (RASHEC) trial, patients with high-risk endometrial cancer were randomly assigned to robot-assisted laparoscopic surgery (RALS) or laparotomy for pelvic and infrarenal para-aortic lymph node dissection. We here report on self-reported lower limb lymphedema (LLL), lymphocyst formation, ascites, and long-term serious adverse events 12 months after surgery.Patients and methodsPatients were enrolled between 2013 and 2016, and 96 patients were included in the per protocol analysis, evenly distributed between RALS and laparotomy. Self-reported LLL was recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for endometrial cancer—EN24, assessed before and 12 months after surgery. Computed tomography was assessed at baseline, 3, and 12 months. Medical charts were reviewed for serious adverse events and hospital admissions 31 to 365 days after surgery.ResultsAt 12 months after laparotomy and RALS, 61% and 50% patients, respectively, reported LLL (p = 0.31). In univariate analysis, the mean score of LLL at 12 months was significantly higher for laparotomy than for RALS (p < 0.05) and for those without abdominal drainage (p = 0.02), but was not independently associated with LLL in the multivariate analysis. Imaging showed no significant difference in lymphocyst formation or ascites between surgical modalities. No difference was found in serious adverse events and admissions to hospital for any reason. There was no agreement between lymphocyst formation or ascites and self-reported LLL.ConclusionFollow-up 1 year after comprehensive surgical staging for high-risk endometrial cancer showed no differences in self-reported LLL, findings on imaging, or SAE between laparotomy and robot-assisted surgery.

Objective: To evaluate the accuracy of preoperative imaging in the diagnosis of cardiophrenic lymph node (CPLN) metastases and to report perioperative outcomes after resection of CPLN at the time of cytoreductive surgery for advanced epithelial ovarian cancer (EOC). Furthermore, to assess clearance of CPLN by postoperative imaging. Methods: All women with stage IIIC/IV EOC subjected to surgery at our institution from January 2014 to October 2016 were retrospectively identified from a database. Among these, women subjected to CPLN resection during surgery were identified. Pre- and postoperative computed tomography (CT) scans, pathology reports, surgical approach and outcomes were reviewed. Results: One hundred and eighty women with stage IIIC/IV EOC subjected to surgery with curative intent were identified. Twenty-four (13%) of these women underwent CPLN resection. All had CT imaging suggestive of CPLN metastases. 20/24 (83%) had confirmed metastases upon final pathology. CPLN resection was associated with longer operation time, more often advanced upper abdominal surgery and more postoperative complications but there was no difference in days from surgery to initiation of chemotherapy. Postoperative CT was still indicative of CPLN metastases in 13/22 (59%) women despite resection with confirmative pathology. Conclusions: Resection of CPLN metastases is highly feasible without considerable added morbidity. Concern regarding surgical clearance is raised since postoperative imaging was indicative of metastases in the majority of women. The prognostic significance of stage IV disease based exclusively on CPLN metastases is unclear and any survival benefit from the procedure is yet to be determined. (Less)

Tubal ligation results in less advanced stages and lower risk of metastatic spread at diagnosis of endometrial cancer (EC) but the primary preventive effect of the procedure is unclear. In a Swedish nationwide population-based cohort study, we crosslinked registry data for tubal ligation, EC, and death for Swedish women between 1973 and 2010. All women were followed until EC, emigration, hysterectomy for non-cancerous reasons, death, or end of follow-up. Primary outcome was incidence of EC and secondary outcome overall survival. We calculated adjusted incidence rates (IR) per 100,000 person-years and hazard ratios (HR) using Cox regression models. A total of 35,711 cases of EC were identified among 5,385,186 women. The IR of EC among exposed was 17.7 (95% CI 15.7-19.9) versus 29.0 (95% CI 28.7-29.3) among unexposed (per 100,000 women years). Exposed individuals had significantly reduced risk of EC (HR 0.73, 95% CI 0.65-0.83). The mortality rate among women with EC was 72% lower in exposed compared to unexposed (IR 1,441; 95% CI 1,089-1,907 and IR 5,136; 95% CI 5,065-5,209, respectively) which following adjustment corresponded to a HR of 0.71 (95% CI 0.49-1.03). Tubal ligation was associated with lower risk of EC as well as mortality rates in women with EC. Elective tubal ligation may be adopted in future cancer preventive strategies but must be balanced against the irreversibility of the procedure, which preclude further unassisted reproduction.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not.

To investigate if robot-assisted laparoscopic surgery (RALS) was non-inferior to laparotomy (LT) in harvesting infrarenal paraaortic lymph nodes in patients with presumed stage I-II high-risk endometrial cancer.Patients with histologically proven endometrial cancer, presumed stage I-II with high-risk tumour features, were randomised to hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy by either RALS or LT. Primary outcome was paraaortic lymph node count. Secondary outcomes were perioperative events, postoperative complications and total health care cost.Overall 120 patients were randomised and 96 patients were included in the per protocol analysis. Demographic, clinical and tumour characteristics were evenly distributed between groups. Mean (±SD) paraaortic lymph node count was 20.9 (±9.6) for RALS and 22 (±11, p = 0.45) for LT. The difference of means was within the non-inferiority margin (-1.6, 95% CI -5.78, 2.57). Mean pelvic node count was lower after RALS (28 ± 10 versus 22 ± 8, p 0.001). There was no difference in perioperative complications or readmissions between the groups. Operation time was longer (p 0.001) but total blood loss less (0.001) and hospital stay shorter (0.001) in RALS group than LT group. Health care costs for RALS was significantly lower (mean difference $1568 USD/€1225 Euro, p 0.05).Our results demonstrate non-inferiority in paraaortic lymph node count, comparable complication rates, shorter hospital length and lower total cost for RALS over laparotomy. Generalisability of the latter finding requires a high-volume setting and high surgical proficiency. In women with high-risk endometrial cancer confined to the uterus, RALS is a valid treatment modality.ClinicalTrials.govNCT01847703.

To investigate the association between hysterectomy and thyroid cancer subtypes based on histopathology. They did a nationwide, population-based, cohort study from 1973 to 2009 in Sweden. All women above 18 years of age during the period between January 1, 1973 and December 31, 2009 from the Register of Population (n = 5.704,202) were identified as the study population. Individual case ascertainment of primary thyroid cancer subtypes were restricted to 1993-2009 based on histological pathologic-anatomical-diagnosis from the Cancer Register. Thyroid cancer subtypes were categorized based on histological morphology as: papillary, follicular and others (including anaplastic and medullary thyroid carcinoma). Information on benign hysterectomy derived from the Swedish Inpatient Register. Women with a hysterectomy (exposed) were compared with women not having had a hysterectomy (unexposed) using Cox's proportional hazard ratios (HRs). The adjusted HR for papillary thyroid cancer was significantly increased in exposed as compared with unexposed women (HR 1.70, 95% CI 1.04-2.79). There was no significant association between hysterectomy and follicular carcinoma or other thyroid cancers. There was a clear shift in the occurrence of thyroid cancer toward a lower attained age at the time of diagnosis among the exposed but no significant difference in overall survival when comparing exposed and unexposed (HR 1.02, 95% CI 0.48-2.16) Hysterectomy was associated with an increased risk for subsequent papillary thyroid cancer and diagnosis at a younger age compared with women not having had a hysterectomy but there were no differences in survival.