Variability of treatment of locally advanced cervical cancer: How French multidisciplinary teams follow European guidelines?

INTRODUCTION: Cervical cancer is a global public health concern. Despite ESGO recommendations and FIGO classification changes, management of locally advanced cervical cancer (LACC) remains debated in France. Our study aimed to review LACC treatment practices and assess adherence to ESGO recommendations among different practitioners. METHODS: From February 2021 to August 2022, we conducted a survey among gynecologic oncology surgeons, radiation oncologists, and medical oncologists practicing in France and managing LACC (FIGO stages IB3-IVA) according to the 2018 FIGO classification. We analyzed responses against the 2018 ESGO recommendations as a "gold standard." RESULTS: Among 115 respondents (56% radiation oncologists, 30% surgeons, 13% medical oncologists), 48.6% of gynecologic surgeons didn't perform para-aortic lymphadenectomy (PAL) with significant radiologic pelvic involvement. PAL, when indicated by PET-CT, was more common in university hospitals (66.7% of surgeons). Surgeons in university hospitals also followed ESGO recommendations more closely. Overall, compliance with all ESGO recommendations was low: 5.7% of surgeons, 21.5% of radiation oncologists, and 60% of medical oncologists. Prophylactic para-aortic irradiation, per ESGO, was more frequent in comprehensive cancer centers (52% of radiation oncologists). CONCLUSION: Adherence to ESGO recommendations for LACC treatment appears low in France, particularly in surgery, with limited PAL in cases of lymph node negativity on PET-CT. However, these recommendations are more often followed by surgeons in university hospitals and radiation oncologists in cancer centers. Adherence to these recommendations may impact patient survival and warrants evaluation of care quality, justifying the organization of LACC management in expert centers.

Tertiary prevention strategies for micrometastatic lymph node cervical cancer: A systematic review and a prototype of an adapted model of care.

PURPOSE: We found a need for balancing the application of clinical guidelines and tailored approaches to follow-up of cervical cancer (CC) patients in the lymph node micrometastatic (MICs) setting. This review aimed to determine the current knowledge of management of MIC-positive CC cases. METHODOLOGY: We addressed prognostic and risk of recurrence monitoring impacts associated with MIC+ cases. The electronic databases for literature and relevant articles were analysed. RESULTS: Fifteen studies, (4882 patients), were included in our systematic review. While the results show that MICs significantly worsen prognosis in early CC. A tertiary prevention algorithm for low volume lymph node disease may stratify follow-up according to the burden of nodal disease and provide data that helps improve follow-up performance. CONCLUSION: MICs worsen prognosis and should be managed as suggested by the algorithm. However, this algorithm must be externally validated. The clinical impact of isolated tumor cells (ITC) remains unclear.

External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. METHODS: We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). RESULTS: We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). CONCLUSION: No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

[Prevalence of menorrhagia among women in Reunion Island]. / Prévalence des ménorragies chez les femmes à la Réunion.

OBJECTIVES: To estimate the prevalence of menorrhagia in women in Reunion Island using the Higham score, to evaluate self-reporting as an alternative diagnostic method, and to study women's level of knowledge about menorrhagia and its impact on their quality of life. METHODS: This was a descriptive, cross-sectional observational study involving 185 adult women with menstrual periods living in Reunion Island. Women volunteered to answer an online self-questionnaire proposed by healthcare professionals from January to May 2023 in Reunion Island. They completed a general information questionnaire, the Higham score, a menorrhagia knowledge questionnaire and a menstrual quality of life questionnaire. RESULTS: The prevalence of menorrhagia in the sample was 48.1% using the Higham score and 46.5% using self-report. Women's level of knowledge about menorrhagia is still insufficient, given the significant impact on quality of life during menstruation among those suffering from this symptom. CONCLUSION: The prevalence of menorrhagia in our sample of women on Reunion Island is high. Measures need to be taken to break the taboos surrounding menstruation, promote menstrual education and foster a better understanding by women of menstrual pathologies, particularly menorrhagia. Early detection of this symptom would enable faster treatment and avoid complications and adverse effects on quality of life.

[Determinants of papillomavirus vaccination in Mayotte: A qualitative study among general practitioners]. / Déterminants et leviers de la vaccination papillomavirus à Mayotte : une étude qualitative chez les médecins généralistes.

OBJECTIVES: In Mayotte, cervical cancer represents the second cause of cancer mortality in women. Vaccination coverage against papillomavirus and screening rates are difficult to quantify but among the lowest in France. Added to this is an under-calibrated health system, which does not allow optimal treatment of cancers on site. The objective of the study was to study the elements that would increase papillomavirus vaccination among general practitioners. METHODS: We carried out a qualitative study of phenomenological inspiration using semi-directed open interviews. The target population was private general practitioners based in Mayotte. The analysis was done by coding verbatim statements, from which emerged general themes, to build a model. RESULTS: Twenty-two interviews were conducted. Vaccination was part of a context and was organized around the trio doctor-patient-institutions. The main pillar to vaccination was information, which could concern doctors or patients. The information delivered to patients through the media, campaigns in schools, and vaccination obligation were the main elements. The study revealed positive emotional dynamics of on-site HPV vaccination. CONCLUSION: This study made it possible to better understand the ecosystem in which papillomavirus vaccination takes place in Mayotte, and to identify elements of vaccination promotion. Vaccination school campaigns should keep going on to increase vaccination uptake.

Predictors of Non-Sentinel Lymph Node Metastasis in Patients with Positive Sentinel Lymph Node in Early-Stage Cervical Cancer: A SENTICOL GROUP Study.

BACKGROUND: The goal of this study was to identify the risk factors for metastasis in the remaining non-sentinel lymph nodes (SLN) in the case of positive SLN in early-stage cervical cancer. METHODS: An ancillary analysis of two prospective multicentric databases on SLN biopsy for cervical cancer (SENTICOL I and II) was performed. Patients with early-stage cervical cancer (FIGO 2018 IA to IIA1), with bilateral SLN detection and at least one positive SLN after ultrastaging, were included. RESULTS: 405 patients were included in SENTICOL I and Il. Fifty-two patients had bilateral SLN detection and were found to have SLN metastasis. After pelvic lymphadenectomy, metastatic involvement of non-SLN was diagnosed in 7 patients (13.5%). Patients with metastatic non-SLN were older (51.9 vs. 40.8 years, p = 0.01), had more often lympho-vascular space invasion (LVSI) (85.7% vs. 35.6%, p = 0.03), and had more often parametrial involvement (42.9% vs. 6.7%, p = 0.003). Multivariate analysis retained age (OR = 1.16, 95% IC = [1.01-1.32], p = 0.03) and LVSI (OR = 25.97, 95% IC = [1.16-582.1], p = 0.04) as independently associated with non-SLN involvement. CONCLUSIONS: Age and LVSI seemed to be predictive of non-SLN metastasis in patients with SLN metastasis in early-stage cervical cancer. Larger cohorts are needed to confirm the results and clinical usefulness of such findings.

Survival after sentinel lymph node biopsy for early cervical cancers: a systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy alone versus pelvic lymphadenectomy is missing. OBJECTIVE: To investigate, with this meta-analysis, the impact of sentinel lymph node biopsy alone versus pelvic lymphadenectomy on survival for patients with early-stage cervical cancer. METHODS: A systematic literature review was performed. We excluded studies in which pelvic lymphadenectomy was systematically performed after every sentinel lymph node biopsy, including only articles where pelvic lymphadenectomy was performed because sentinel lymph node biopsy was not conclusive. A meta-analysis was carried out combining 5-year disease-free survival and overall survival rates with a random and fixed effect model. Heterogeneity was tested using the Cochran Χ2 test and quantified with Higgins information I2. RESULTS: The search of databases and registers found 927 items and six articles (two retrospective and four prospective). The median time of follow-up was 34.8 months (range 13-53). Overall common effect disease-free survival was 98% while random effect disease-free survival was 94%. Overall heterogeneity was 77%. A subgroup analysis was applied, dividing studies into one group including sentinel lymph node biopsy negative data only (common effect disease-free survival 91%; random effect disease-free survival 90%), and one group with a negative and positive sentinel lymph node biopsy (common effect disease-free survival 98%; random effect disease-free survival 96%). In the analysis of overall survival, positive and negative sentinel lymph node biopsy cases were examined together (common and random effect overall survival 99%). Ultrastaging did not affect disease-free survival (common and random effect disease-free survival 92% in the ultrastaging group vs common effect disease-free survival 99% and random effect disease-free survival 96% in the non-ultrastaging group). CONCLUSIONS: Both 5-year disease-free survival and overall survival rate after sentinel lymph node biopsy alone are higher than 90% and do not differ from pelvic lymphadenectomy survival data. Ultrastaging did not impact survival.

Ovarian Follicular Response Is Altered by Salpingectomy in Assisted Reproductive Technology: A Pre- and Postoperative Case-Control Study.

Objectives: The goal of this study was to assess the effect of unilateral salpingectomy on the number of mature follicles in the ipsilateral ovary during an assisted reproductive technology (ART) stimulation cycle, as compared to the contralateral ovary. Methods: This was a retrospective, single-center, case-control cohort study conducted from 2017 to 2022. Patients from 18 to 43 years old who underwent at least one ART cycle before and after a unilateral salpingectomy were included. The number of recruited follicles, including mature (≥16 mm) and intermediate follicles (13-15.5 mm), on the salpingectomy side (case) were compared to those present on the contralateral ovary (control) during an ART attempt. To take into account the inter-ovarian variability, the comparison was performed on two ART cycles, performed before then after the salpingectomy. Results: Overall, 24 patients were included in our study. While the number of mature follicles was similar in both ovaries before surgery, the mean number of mature follicles was significantly reduced after salpingectomy in the operated side, as compared to the control side, being, respectively 3.00 vs. 5.08 (p = 0.048). There was no significant difference between the intermediate and total recruited follicles. Conclusions: Our study suggests that salpingectomy may impact the follicle recruitment on the ipsilateral side by altering the vascularization during mesosalpinx coagulation. Gynecologists should be mindful of this concept and accurately set surgical indications. Beyond the indication, this emphasizes the critical role of having infertility surgeons sensitive to fertility preservation for optimal management of ART patients. Further studies with larger patient populations are required to confirm these results.

Management of patients with advanced epithelial ovarian cancer: a European survey.

BACKGROUND: The aim of this study was to assess current European practices in the management of patients with advanced epithelial ovarian cancer in 2021. METHODS: A 58-question electronic survey was distributed anonymously to the members of six European learned societies. Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. RESULTS: A total of 171 participants from 17 European countries responded to emailed surveys. Most participants were experienced practitioners (superior than 15 years of experience) specializing in gynecology-obstetrics (29.8%), surgical oncology (25.1%), and oncogynecology (21.6%). According to most (64.8%) participants, less than 50% of patients were eligible for primary debulking surgery. Variations in the rate of primary debulking surgery depending on the country of origin of the practitioners were observed in this study. The LION study criteria were applied in 70.4% of cases during PDS and 27.1% after chemotherapy. In cases of BRCA1-2 mutations, olaparib was given by 75.0-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. CONCLUSIONS: This study sheds light on current practices and attitudes regarding the management of patients with advanced epithelial ovarian cancer in Europe in 2021.

[Application in France of the 2021 European recommendations on endometrial cancer]. / Application en France des recommandations européennes 2021 sur le cancer de l'endomètre.

The latest European recommendations of the European Societies of Gynecological Oncology (ESGO), Radiotherapy and Oncology (ESTRO) and Anatomopathology (ESP) concerning the management of patients with endometrial cancer were published in 2021. On behalf of the French Society of Gynecologic Oncology (SFOG) and the SFOG campus, we wish to summarize for the French-speaking readership the main measures with a more specific application for France. We also incorporate data from a Delphi survey conducted with a panel of French and French-speaking Swiss experts. The data presented in this article relate to histo-molecular characteristics, radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, and metastatic cancers. The aim of this review article is to show the application of the latest international recommendations to clinicians and pathologists for the implementation of these recommendations.

Management of Endometrial Cancer: French Society of Onco-Gynecology's Evaluation through a Delphi Survey.

Our aim was to assess the opinion of a panel of experts and obtain a consensus on the management of endometrial cancer in France and French Switzerland. A Delphi survey was carried out among a panel of French and French-speaking Swiss experts. The first questionnaire included 65 questions divided into eight categories: characterization of experts, histo-molecular characteristics and radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, high-risk, and metastatic cancers. The experts were asked to reply on a 9-point scale, both on the validity and the clarity of each question. After the answers were analyzed, a second questionnaire was sent to the same experts. The study took place between December 2021 and March 2022. Further, 58 (57.4%) of the 101 experts responded in the first round, and 39 recommendations were obtained (60%). Six questions were voted redundant and 20 discordant. These questions were reformulated, and, at the end of the second round, 17 recommendations were validated (85%). In total, the study presents an analysis of 56 questions and related responses. Expert advice helps to clarify non-consensual issues, standardize the management of endometrial cancer, and optimize clinical practices.

Women with Cervical High-Risk Human Papillomavirus: Be Aware of Your Anus! The ANGY Cross-Sectional Clinical Study.

Anogenital human papillomaviruses (HPV) are highly prevalent in sexually active populations, with HR-HPV being associated with dysplasia and cancers. The consequences of cervical HPV infection are well-known, whereas those of the anus are less clear. The correlation of cervical and anal HPVs with the increasing number of anal cancers in women has not been studied yet. The objective of our prospective study was to determine whether cervical and anal HPV correlated in a cohort of women recruited in a university hospital in Switzerland. Recruitment was conducted in the gynecology clinic, the colposcopy clinic, and the HIV clinic. Cervical and anal HPV genotyping and cytology were performed. Overall, 275 patients were included (360 were initially planned), and among them, 102 (37%) had cervical HR-HPV. Patients with cervical HR-HPV compared to patients without cervical HR-HPV were significantly younger (39 vs. 44 yrs, p < 0.001), had earlier sexual intercourse (17.2 vs. 18.3 yrs, p < 0.01), had more sexual partners (2.9 vs. 2.2, p < 0.0001), more dysplastic cervical cytology findings (42% vs. 19%, p < 0.0001) and higher prevalence of anal HR-HPV (59% vs. 24%, p < 0.0001). Furthermore, the HR-HPV group reported more anal intercourse (44% vs. 29%, p < 0.015). Multivariate analysis retained anal HR-HPV as independent risk factor for cervical HR-HPV (OR3.3, CI 1.2−9.0, p = 0.02). The results of this study emphasize that it is of upmost importance to screen women for anal HR-HPV when diagnosing cervical HR-HPV.

Prevalence of anal dysplasia and HPV genotypes in gynecology patients: The ANGY cross-sectional prospective clinical study protocol.

BACKGROUND: Human Papillomaviruses (HPV) are highly prevalent in the sexually active populations, with a significant burden in terms of health and psychological cost in all class ages. High-risk (HR) HPV genotypes are associated with anogenital dysplasia and cancers, and anal HPV-induced cancer is increasingly observed in women. The interactions of HPV genotype's between the anus and the cervix, and the subsequent occurrence of dysplasia remains unclear. This clinical study set out to test the hypothesis that risk factors for anal HR-HPV and dysplasia may differ in women with or without cervical dysplasia or in HIV-positive women. METHODS: Cervical and anal HPV genotypes and cytology testing will be performed prospectively in a cohort of women recruited in a tertiary university hospital in Switzerland. Women will be allocated to three groups: 1) normal previous cervical smear; 2) high-grade cervical dysplasia (H-SIL) at previous cervical smear; 3) HIV+, independently of previous cervical smear result. General inclusion criteria comprised the followings: Female-Age > = 18 years; Satisfactory understanding of French; No objection to HIV testing. Specific inclusion criteria are: Group 1, no past or current gynecological dysplasia and HIV negative; Group 2, Gynecological dysplasia (H-SIL) or carcinoma in situ demonstrated by histology (vulvar, vaginal or cervical) and HIV negative; Group 3: HIV-positive (regardless of viremia or CD4 count) with or without gynecological dysplasia. General exclusion criteria are: Pregnancy; History of anal dysplasia/cancer; Status after pelvic radiotherapy; Absence of anus and anal canal. Estimated prevalences of anal dysplasia are: in group 1, 1% (0-2%); in group 2, 15% (5-27%), and in group 3, 30% (19-45%). With a 10% margin error, a sample size of 120 women per group is required to reach 90% power for detecting statistical significance (unilateral α error of 5%). DISCUSSION: The primary endpoint is the prevalence of anal and cervical dysplasia, and description of the respective HPV genotypes in each group. The results of this study could improve the standard of screening of cervical and anal dysplasia in women through evidence of concomitant presence of HPV's and/or dysplasia in anus or cervix to support vaccination for instance. Beginning of recruitment started in September 2016. Results should be presented in end of 2022. Preliminary analysis for first 100 patients reveals that the mean age of the population is 39.6 (± 10.9) years with mean age of first sexual intercourse of 18.5 (± 3.9) years. In this cohort, 12% are vaccinated and 38% having had anal intercourse. Overall, 43% of the studied population had cervical HR-HPV in the studied population, and 53% had normal cytology. Anal LR HPV and HR HP were found in 27.6% and 38.4% of all patients respectively. Eighty percent had normal anal cytology. Groups 1,2 and 3 had a significant difference in terms of age, gestity, parity, age of first sexual intercourse, systematic use of condom, number of cervical LR HPV and HR HPV and abnormal cervical cytologies. TRIAL REGISTRATION: The study was approved by the institutional review board-CER-VD#2015-00200-on the 29th of June 2016 and is registered on the Swiss National Clinical Trials Portal (SNCTP), SNCTP000002567, Registered 29 June 2016, https://www.kofam.ch/en/snctp-portal/study/40742/.

Analysis of Predictive Factors for Successful Vascular Anastomoses in a Sheep Uterine Transplantation Model.

Uterine transplantation is becoming an increasingly realistic therapeutic for uterine infertility. Surgical training on large animal models such as sheep is a prerequisite for establishing a program in humans. The objective of our study was to analyze the predictive factors for successful vascular anastomoses. We performed 40 autotransplants that involved end-to-side anastomoses from the uterine to the external iliac vessels. We analyzed vessel results in terms of success or failure; a total of 78.7% of arterial and 82.9% of venous anastomoses were successful in the immediate postoperative period. In multivariate analysis, independent factors associated with immediate successful vein anastomoses were as follows: a short warm ischemia time (<2 h, OR = 0.05; 95% CI [0.003−0.88], p = 0.04), the absence of any anastomotic complications (OR = 0.06; 95% CI [0.003−0.099], p = 0.049), and their realization by a vascular surgeon (OR = 29.3; 95% CI [1.17−731.9], p = 0.04). Secondly, we showed that an increase in lactate levels greater than 2.72 mmol/L, six hours after reperfusion was predictive of failure, with a sensibility of 85.7% and a specificity of 75.0%. In order to perfect the management of vascular anastomoses by a vascular surgeon, training on animal models and in microsurgery are mandatory in establishing a uterine transplantation program in humans.

Temporary cervical sling and uterine twist before B-Lynch for massive uterine bleeding after delivery.

Massive uterine bleeding occurring after delivery is in most cases unpredictable and can have fatal consequences. This article presents the technique of combining the twisting of uterus on a 90° rotation on its axis and positioning a sling around the cervix, allowing to decrease incoming blood flow from uterine and ovarian arteries. The aim of this easy-to-use procedure is to enable surgeons and anaesthesiologists to respectively ensure the presence of an experienced surgeon and to stabilise the haemodynamic of the patient. It is a modus operandi of particular interest in resources' challenged environments.

Surgical management of patients with advanced ovarian cancer: Results of a French National Survey.

INTRODUCTION: Desire to homogenize advanced stage ovarian cancer management has led to a debate on the need to centralize cares. The aim was to assess current practices to compare them with centralization motivation and to overview possible perspectives of evolution. METHODS: An anonymous questionnaire of 57 questions has been submitted from August 2021 to October 2021 to members of French gynecological oncological surgical societies. Questions encompassed all aspects of ovarian cancer surgical management, including institutions, technics, indications, and outcomes. RESULTS: Of the 40 responses, 77.5% managed less than 20 cases by themselves, but 67.5% practiced in institution managing more than 30 cases annually. Since the LION trial results' publication, 95% of practitioners have evolved their lymphadenectomy indications. More than 10% of surgery needed digestive resection for 90% of practitioners. Digestive resections rate was significantly higher for practitioners managing more than 20 cases (p<0.01), but it was not for institutions managing more than 30 cases annually (p=0,07). Surgeons performing more than 20 ovarian cancers annually reported less severe complications (p=0.04) compared to low-volume surgeons independently of institution volume. For more than a quarter of the practitioners, less than half of the patients can benefit from the enhanced recovery after surgery program despite benefits of such care. CONCLUSION: Our survey provides an overview of French practices in ovarian cancer management. This survey seems to confirm that minimum volume thresholds could lead to better outcomes. It also underlines that individual performances are as valuable as center volume.

Estimation risk of lymph nodal invasion in patients with early-stage cervical cancer: Cervical cancer application.

Introduction: Lymph node status is a major prognostic factor in early-stage cervical cancer. Predicting the risk of lymph node metastasis is essential for optimal therapeutic management. The aim of the study was to develop a web-based application to predict the risk of lymph node metastasis in patients with early-stage (IA1 with positive lymph vascular space invasion, IA2 and IB1) cervical cancer. Materials and methods: We performed a secondary analysis of data from two prospective multicenter trials, Senticol 1 and 2 pooled together in the training dataset. The histological risk factors were included in a multivariate logistic regression model in order to determine the most suitable prediction model. An internal validation of the chosen prediction model was then carried out by a cross validation of the 'leave one out cross validation' type. The prediction model was implemented in an interactive online application of the 'Shinyapp' type. Finally, an external validation was performed with a retrospective cohort from L'Hôtel-Dieu de Québec in Canada. Results: Three hundred twenty-one patients participating in Senticol 1 and 2 were included in our training analysis. Among these patients, 280 did not present lymph node invasion (87.2%), 13 presented isolated tumor cells (4%), 11 presented micrometastases (3.4%) and 17 macrometastases (5.3%). Tumor size, presence of lymph-vascular space invasion and stromal invasion were included in the prediction model. The Receiver Operating Characteristic (ROC) Curve from this model had an area under the curve (AUC) of 0.79 (95% CI [0.69- 0.90]). The AUC from the cross validation was 0.65. The external validation on the Canadian cohort confirmed a good discrimination of the model with an AUC of 0.83. Discussion: This is the first study of a prediction score for lymph node involvement in early-stage cervical cancer that includes internal and external validation. The web application is a simple, practical, and modern method of using this prediction score to assist in clinical management.

Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study.

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.