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Endometriosis is a benign inflammatory onco-mimetic disease affecting 10–15% of women in the world. When it is refractory to medical treatments, surgery may be required. Usually, laparoscopy is the preferred approach, but robotic surgery has gained popularity in the last 15 years. This study aims to evaluate the safety and efficacy of robotic-assisted laparoscopic surgery (RAS) versus conventional laparoscopic surgery (LPS) in the treatment of endometriosis. This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting perioperative data comparing RAS and LPS surgery in patients with endometriosis querying PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for the quality assessment of the selected articles. Fourteen studies were identified, including 2709 patients with endometriosis stage I-IV for the meta-analysis. There were no significant differences between RAS and LPS in terms of intraoperative and postoperative complications, conversion rate and estimated blood loss. However, patients in the RAS group have a longer operative time (p < 0.0001) and longer hospital stay (p = 0.020) than those in the laparoscopic group. Robotic surgery is not inferior to laparoscopy in patients with endometriosis in terms of surgical outcomes; however, RAS requires longer operative times and longer hospital stay. The benefits of robotic surgery should be sought in the easiest potential integration of robotic platforms with new technologies. Prospective studies comparing laparoscopy to the new robotic systems are desirable for greater robustness of scientific evidence.

OBJECTIVE: Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. METHODS: The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. RESULTS: Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-inte

Objective: The growing adoption of molecular and genomic characterization is changing the current landscape of treatment of endometrial cancer patients. Using the surrogate molecular classification, endometrial cancer patients can be classified in four subgroups: POLE mutated (POLEmut), MMRd/MSI-H, p53 abnormal (p53abn), and no specific mutational profile (NSMP). However, some patients can harbor two or more molecular features (defined as multiple classifier). Since the rarity of this occurrence, evidence regarding multiple classifiers is still limited. Here, we described characteristics and outcomes of multiple classifiers.Methods: This is a multi-institutional retrospective study. Data of consecutive patients having 2 or more molecular features were collected. Survival was assessed using the Kaplan-Meier and Cox proportional hazard methods.Results: Charts of 72 multiple classifiers were reviewed. Median (range) follow-up was 9.8 (1.2, 37.5) months. Overall, 31 (43%) patients had POLEmut. Patients with POLEmut-MMRd/MSI-H, POLEmut-p53abn, and POLEmut-MMRd/MSI-H-p53abn were 6 (8.3%), 20 (27.8%), and 5 (6.9%), respectively. Among those 31 patients, no recurrence occurred within a median follow-up of 10.5 months (only seven (22.6%) patients had at least 2-year follow-up). The remaining 41 (56.9%) patients were diagnosed with tumors harboring both p53 and MMRd/MSI-H. Among them, four (9.8%) recurrences occurred at a median follow-up time of 8.9 months. Adjuvant therapy (other than vaginal brachytherapy) was administered in 5/31 (16%) and 25/41 (61%) patients with and without POLEmut, respectively (p < 0.001).Conclusions: Multiple classifiers endometrial cancer with POLEmut are characterized by good prognosis even in case of presence of MMRd/MSI-H and/or p53abn. Additional studies with long-term follow-up are needed.

Introduction: Endometrial cancer (EC) is the only gynecologic malignancy showing increasing trends in incidence and mortality. While standard treatment has been effective primarily for early-stage EC, precision medicine with tailored therapy has revolutionized the management of this disease. Genome sequencing analyses have identified four sub-types of EC. Treatments for primary and metastatic disease can now be tailored more accurately to achieve better oncologic results. Areas covered: This review provides an overview of the most relevant and updated evidence in the literature regarding EC molecular analysis and its role in risk classification, prognostication, and guidance for tailored and target therapies in early and advanced/metastatic stages. In addition, it provides updated information on optimal surgical management based on molecular classification and highlights key advances and future strategies. Expert opinion: EC molecular analysis yields the potential of tailoring adjuvant treatment by escalating or deescalating therapy, as shown for POLE-mutated and p53-mutated tumors. Moreover, the expression of specific molecular signatures offers the possibility to employ novel target therapies, such as immune-checkpoint inhibitors that have demonstrated a significant benefit on prognosis. New treatment guidelines are still being established, and ongoing studies are exploring the potential prognostic role of further sub-stratifications of the four molecular classes and treatment options.

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

Background: Endometrial cancer recurrence occurs in about 18 % of patients. This study aims to analyze the pattern recurrence of endometrial cancer and the relationship between the initial site of primary disease and the relapse site in patients undergoing surgical treatment. Methods: We retrospectively reviewed all surgically treated patients with endometrial cancer selecting those with recurrence. We defined primary site disease as uterus, lymph nodes, or peritoneum according to pathology analysis of the surgical specimen. The site of recurrence was defined as vaginal cuff, lymph nodes, peritoneum, and parenchymatous organs. Our primary endpoint was to correlate the site of initial disease with the site of recurrence. Results: The study enrolled 1416 patients. The overall recurrence rate was 17,5 % with 248 relapses included in the study. An increase of 9.9, 5.7, and 5.7 times in the odds of relapse on the lymph node, peritoneum, and abdominal parenchymatous sites respectively was observed in case of nodal initial disease (p < 0.001). A not significant difference in odds was observed in terms of vaginal cuff relapse (OR 0.9) between lymph node ad uterine primary disease (p = 0.78). An increasing OR of 8.7 times for nodal recurrences, 46.6 times for peritoneum, and 23.3 times for parenchymatous abdominal recurrences were found in the case of primary peritoneal disease (p < 0.001). Conclusion: Endometrial cancer tends to recur at the initial site of the disease. Intraoperative inspection of the adjacent sites of primary disease and targeted instrumental examination of the initial sites of disease during follow-up are strongly recommended.

Indocyanine green (ICG), a well-known molecule employed in medicine for over five decades, has emerged as a versatile dye widely embraced across various surgical disciplines. In gynecologic oncology, its prevalent use revolves around the detection of sentinel lymph nodes. However, the true potential of ICG extends beyond this singular application, owing to its pragmatic utility, cost-effectiveness, and safety profile. Furthermore, ICG has been introduced in the theranostic landscape, marking a significant juncture in the evolution of its clinical utility. This narrative review aims to describe the expanding horizons of ICG fluorescence in gynecologic oncology, beyond the sentinel lymph node biopsy. The manifold applications reported within this manuscript include: 1) lymphography; 2) angiography; 3) nerve visualization; 4) ICG-driven resections; and 5) theranostic. The extensive exploration across these numerous applications, some of which are still in the pre-clinical phase, serves as a hypothesis generator, aiming to stimulate the development of clinical studies capable of expanding the use of this drug in our field, enhancing the care of gynecological cancer patients.

Objective: The growing adoption of molecular and genomic characterization is changing the current landscape of treatment of endometrial cancer patients. Using the surrogate molecular classification, endometrial cancer patients can be classified in four subgroups: POLE mutated (POLEmut), MMRd/MSI-H, p53 abnormal (p53abn), and no specific mutational profile (NSMP). However, some patients can harbor two or more molecular features (defined as multiple classifier). Since the rarity of this occurrence, evidence regarding multiple classifiers is still limited. Here, we described characteristics and outcomes of multiple classifiers. Methods: This is a multi-institutional retrospective study. Data of consecutive patients having 2 or more molecular features were collected. Survival was assessed using the Kaplan-Meier and Cox proportional hazard methods. Results: Charts of 72 multiple classifiers were reviewed. Median (range) follow-up was 9.8 (1.2, 37.5) months. Overall, 31 (43%) patients had POLEmut. Patients with POLEmut-MMRd/MSI-H, POLEmut-p53abn, and POLEmut-MMRd/MSI-H-p53abn were 6 (8.3%), 20 (27.8%), and 5 (6.9%), respectively. Among those 31 patients, no recurrence occurred within a median follow-up of 10.5 months (only seven (22.6%) patients had at least 2-year follow-up). The remaining 41 (56.9%) patients were diagnosed with tumors harboring both p53 and MMRd/MSI-H. Among them, four (9.8%) recurrences occurred at a median follow-up time of 8.9 months. Adjuvant therapy (other than vaginal brachytherapy) was administered in 5/31 (16%) and 25/41 (61%) patients with and without POLEmut, respectively (p < 0.001). Conclusions: Multiple classifiers endometrial cancer with POLEmut are characterized by good prognosis even in case of presence of MMRd/MSI-H and/or p53abn. Additional studies with long-term follow-up are needed.

Objective: The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. Methods: Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1–2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. Results: 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5–52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06–0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07–0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). Conclusion

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Objective: To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients. Materials and methods: This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers. Results: The study population included 398 (69.5%) and 174 (30.5%) patients having hysterectomy and hysterectomy plus SNM. As the results of the adoption of a propensity-score matched analysis, we selected two homogeneous cohort of patients (150 having hysterectomy only vs. 150 having hysterectomy plus SNM). The SNM group had a longer operative time, but did not correlate with length of hospital stay and estimated blood loss. Overall severe complication rates were similar between groups (0.7% in the hysterectomy group vs. 1.3% in the hysterectomy plus SNM group; p = 0.561). No lymphatic-specific complication occurred. Overall, 12.6% of patients having SNM were diagnosed with disease harboring in their lymph nodes. Adjuvant therapy administration rate was similar between groups. Considering patients having SNM, 4% of patients received adjuvant therapy on the basis of nodal status alone; all the other patients received adjuvant therapy also on the basis of uterine risk factors. Five-year disease-free (p = 0.720) and overall (p = 0.632) survival was not influenced by surgical approach. Conclusions: Hysterectomy (with or without SNM) is a safe and effective method for managing EC patients. Potentially, these data support the omission of side specific lymphadenectomy in case of unsuccessful mapping. Further evidence is warranted in to confirm the role SNM in the era of molecular/genomic profiling.

OBJECTIVE: Sentinel lymph node (SLN) mapping represents the standard approach in uterine confined endometrial cancer patients. The aim of this study was to evaluate the anatomical distribution of SLNs and the most frequent locations of nodal metastasis. METHODS: This was an observational retrospective multicenter study involving eight high volume gynecologic cancer centers in Italy. We reviewed 1576 patients with a histologically confirmed diagnosis of endometrial cancer from September 2015 to June 2020. All patients underwent total hysterectomy with salpingo-ophorectomy and SLN mapping. RESULTS: A total of 3105 SLNs were mapped and removed, 2809 (90.5%) of these were bilateral and 296 (9.5%) unilateral. The overall detection rate was 93.4% (77.9% bilateral and 15.5% unilateral). The majority of SLNs (80%) and positive SLNs (77.8%) were found at the external iliac and obturator level in both endometrioid and non-endometrioid endometrial cancer. Negative SLNs were more frequent in patients with endometrioid compared with non-endometrioid cancer (91.9% vs 86.1%, p<0.0001). Older patients, a higher body mass index, and non-endometrioid histology were more likely to have 'no mapping' (p<0.0001). Univariate and multivariate analysis showed that higher body mass index and age at surgery were independent predictive factors of empty node packet and fat tissue (p=0.029 and p<0.01, respectively). CONCLUSION: The most frequent sites of SLNs and metastases were located in the pelvic area below the iliac vessel bifurcation. Our findings showed that older age, a higher body mass index, and non-endometrioid histology had a negative impact on mapping.

Item does not contain fulltext, BACKGROUND: The molecular classification of endometrial cancer revolutionized our knowledge of its biology but so far has not affected our surgical approach. The exact risk of extra-uterine metastasis and hence the type of surgical staging for each of the four molecular subgroups are currently unknown. PRIMARY OBJECTIVE: To determine the association between molecular classification and disease stage. STUDY HYPOTHESIS: Each endometrial cancer molecular subgroup has a specific pattern of spread and this pattern of spread could guide the extent of surgical staging. TRIAL DESIGN: Prospective, multicenter study MAJOR INCLUSION/EXCLUSION CRITERIA: Participants eligible for inclusion in this study must meet all the following criteria: women ≥18 years with primary endometrial cancer, any histology and stage. PRIMARY ENDPOINT: Number and site of metastasis in each endometrial cancer molecular subgroup. SAMPLE SIZE: 1000 patients will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The trial will last 6 years: 4 years of accrual, and 2 years of follow-up of all patients. Results on staging and oncological outcomes are expected in 2027 and 2029, respectively. TRIAL REGISTRATION: The study has been accepted by UZ Leuven Ethical Committee. Belg. Reg. nr: B3222022000997.

Laparoscopic surgery underwent great improvements during the last few years. This review aims to compare the performance of Trainee Surgeons using 2D versus 3D/4 K laparoscopy. A systematic review of the literature was done on Pubmed, Embase, Cochrane's Library and Scopus. The following words and key phrases have been searched: "Two-dimensional vision", "Three-dimensional vision", "2D and 3D laparoscopy", "Trainee surgeons". This systematic review was reported according to the PRISMA statement 2020. PROSPERO registration No. CRD42022328045. Twenty-two randomized controlled trials (RCTs) and two observational studies were included in the systematic review. Two trials were carried out in a clinical setting, and twenty-two trials were performed in a simulated setting. In studies involving the use of a box trainer, the number of errors in the 2D laparoscopic group was significantly higher than in the 3D laparoscopic group during the performance of FLS skill tasks: peg transfer (MD: -0.82; 95% CI - 1.17 to - 0.47; p < 0.00001), cutting (MD: - 1.09; 95% CI - 1.50 to - 0.69 p < 0.00001), suturing (MD: - 0.48; 95% CI - 0.83 to - 0.13 p = 0.007), However, in clinical studies, there was no significant difference in the time taken for laparoscopic total hysterectomy (MD: 8.71; 95% CI - 13.55 to 30.98; p = 0.44) and vaginal cuff closure (MD: 2.00; 95% CI - 0.72 to - 4.72; p = 0.15) between 2D group and 3D group. 3D laparoscopy facilitates learning for novice surgeons and shows improvements in their laparoscopic performance.

This review provides a comprehensive update on recent evidence regarding gynecologic tumors associated with Lynch Syndrome (LS). Endometrial cancer (EC) and ovarian cancer (OC) are the first and second most common gynecologic malignancies in developed countries, respectively, and LS is estimated to be the hereditary cause in 3% of both EC and OC. Despite the increasing evidence on LS-related tumors, few studies have analyzed the outcomes of LS-related EC and OC stratified by mutational variant. This review aims to provide a comprehensive overview of the literature and comparison between updated international guidelines, to help outline a shared pathway for the diagnosis, prevention, and management of LS. Through the widespread adoption of the immunohistochemistry-based Universal Screening, LS diagnosis and identification of mutational variants could be standardized and recognized by international guidelines as a feasible, reproducible, and cost-effective method. Furthermore, the development of a better understanding of LS and its mutational variants will support our ability to better tailor EC and OC management in terms of prophylactic surgery and systemic treatment in the light of the promising results shown by immunotherapy.

Gynecological malignancies currently affect about 3.5 million women all over the world. Imaging of uterine, cervical, vaginal, ovarian, and vulvar cancer still presents several unmet needs when using conventional modalities such as ultrasound, computed tomography (CT), magnetic resonance, and standard positron emission tomography (PET)/CT. Some of the current diagnostic limitations are represented by differential diagnosis between inflammatory and cancerous findings, detection of peritoneal carcinomatosis and metastases <1 cm, detection of cancer-associated vascular complications, effective assessment of post-therapy changes, as well as bone metabolism and osteoporosis assessment. As a result of recent advances in PET/CT instrumentation, new systems now offer a long-axial field-of-view (LAFOV) to image between 106 cm and 194 cm (i.e., total-body PET) of the patient’s body simultaneously and feature higher physical sensitivity and spatial resolution compared to standard PET/CT systems. LAFOV PET could overcome the forementioned limitations of conventional imaging and provide valuable global disease assessment, allowing for improved patient-tailored care. This article provides a comprehensive overview of these and other potential applications of LAFOV PET/CT imaging for patients with gynecological malignancies.

Objective: This international study aimed to investigate the impact of substage, histological type and other prognostic factors on long-term survival for stage I ovarian carcinoma. Methods: Our study was a retrospective multicenter cohort study that included patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I (IA-IC3) ovarian carcinoma treated at four European referral centers in Germany and Italy. Using Kaplan-Meier survival curves we compared overall and disease-free survival between the different stage I groups. Results: A total of 1115 patients were included. Of these, 48.4% (n=540) were in stage IA, 6.6% (n=73) stage IB, and 45% (n=502) stage IC, of the latter substage IC1, 54% (n=271), substage IC2, 31.5% (n=158), and substage IC3, 14.5% (n=73). Five-year overall and disease-free survival rates for the entire cohort were 94% and 86%, respectively, with no difference between stage IA and IB. However, there was a significantly better overall and disease-free survival for stage IA as compared with stage IC (p=0.007 and p<0.001, respectively). Multivariate analysis revealed incomplete/fertility-sparing staging (HR 1.95; 95% CI 1.27 to 2.99, and HR 3.54; 95% CI 1.83 to 6.86, respectively), and stage IC (HR 2.47; 95% CI 1.63 to 3.75) as independent risk factors for inferior disease-free survival, while low-grade endometrioid (HR 0.42; 95% CI 0.25 to 0.72) and low-grade mucinous (HR 0.17; 95% CI 0.06 to 0.44) histology had superior disease-free survival. Considering overall survival, stage IC (HR 2.41; 95% CI 1.45 to 4.01) and older age (HR 2.41; 95% CI 1.46 to 3.95) were independent risk factors. Conclusion: Although stage I ovarian carcinoma exhibited excellent outcomes, the prognosis of patients with stage IA differs significantly compared with stage IC. Sub-optimal staging as an indicator for quality of care, and tumor biology defined by histology (low-grade endometrioid/mucinous) independently impact disease-free survival.

Objective The main objective of the study was to assess the influence of different clinical and therapeutic variables on the oncological outcomes of patients with endometrial cancer relapse. In particular, we evaluated the impact of cytoreductive surgery with the achievement of complete gross resection. Methods This is a multicenter retrospective cohort study conducted in three centers in Italy and including all patients with first relapse of endometrial cancer from January 2010 to December 2021. Results Data from 331 women with recurrent endometrial cancer were analyzed. Secondary cytoreductive surgery was performed in 56.2% of cases (186 patients). Complete gross resection was achieved in 178 patients (95.7%). Complete gross resection conferred a statistically significant survival benefit both for post-relapse survival and post-relapse free survival (3 years post-relapse survival: 75.4% vs 56.4%, p<0.001; 3 years post-relapse free survival: 32.6% vs 26.5%, p=0.027). At multivariate Cox regression analysis, age ≥75 years, Eastern Cooperative Oncology Group Performance Status ≥2, the advanced-metastatic risk group, complete gross resection, and multiple site relapses were identified as independent significant predictors for post-relapse survival; regarding post-relapse free survival, only age ≥75, the high and advanced-metastatic risk groups, and complete gross resection confirmed their statistical significance. Conclusions Secondary cytoreductive surgery with achievement of complete gross resection was confirmed to be an independent positive predictor for survival in patients with recurrent endometrial cancer and should be considered a valid primary treatment in the therapeutic decision-making process.

Objective: The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. Methods: Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1–2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. Results: 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5–52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06–0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07–0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). Conclusion

Objective Sentinel lymph node mapping by intracervical indocyanine green injection is the preferred method for surgical staging in endometrial cancer. Adverse reactions to indocyanine green are extremely rare, and information about the safety of this tracer in patients with a history of other allergies, asthma, or comorbidities is limited. We aim to evaluate the rate of adverse reactions to indocyanine green injected during sentinel lymph node mapping in patients with endometrial cancer and review the etiology of such reactions. Methods All patients with endometrial cancer undergoing sentinel lymph node mapping with indocyanine green cervical stroma injection at the Mayo Clinic in Rochester, Minnesota between June 2014 and December 2018 were retrospectively evaluated. Any adverse reaction occurring intra-operatively or within 7 days after surgery was identified. A thorough chart review was performed by an allergy specialist physician for any patient with an allergic-type reaction. Results We included 923 patients of which 565 (61.2%) had a history of allergy to antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), other medications, and/or environmental exposures. Of 490 patients who had previously received contrast media, 25 (5.1%) had a history of an adverse reaction. No immediate anaphylaxis or other allergic reactions were observed after indocyanine green injection. 10 (1.1%) patients developed a transient skin reaction within 7 days after surgery. None of these patients had a history of contrast media reaction. Based on timing and clinical/peri-operative history of affected patients, it was determined that skin reactions were likely induced by other newly prescribed medications or contact sensitivity, not administration of indocyanine green. Conclusion Indocyanine green injection for sentinel lymph node mapping in patients with endometrial cancer caused no immediate/delayed anaphylactic or other severe allergic reactions. This included patients with a hi

Objective Endometrial cancer is the most common gynecologic neoplasm. To date, international guidelines recommend sentinel lymph node biopsy for low-risk neoplasms, while systematic lymphadenectomy is still considered for high-risk cases. This study aimed to compare the long-term survival of high-risk patients who were submitted to sentinel lymph node biopsy alone versus systematic pelvic lymphadenectomy. Methods Patients with high-risk endometrial cancer according to the 2021 European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology risk classification were retrospectively analyzed. The primary aim of the study was to compare the long-term overall survival and disease-free survival of high-risk endometrial cancer patients undergoing sentinel lymph node biopsy versus systematic lymphadenectomy. A supplementary post-hoc survival analysis of cases with nodal metastasis was performed to compare sentinel lymph node and lymphadenectomy survival outcomes in this subset of patients. Results The study enrolled 237 patients with histologically proven high-risk endometrial cancer. Patients were followed up for a median of 31 months (IQR 18-40). During the follow-up, 38 (16.0%) patients had a recurrence, and 19 (8.0%) patients died. Disease-free survival (85.2% vs 82.8%; p=0.74) and overall survival (91.3% vs 92.6%; p=0.62) were not different between the sentinel lymph node alone and lymphadenectomy groups. Furthermore, neither overall survival (96.1% vs 91.4%; p=0.43) nor disease-free survival (83.7% vs 76.4%; p=0.46) were different among sentinel lymph node alone and lymphadenectomy groups in patients with nodal metastasis. Conclusions Sentinel lymph node mapping alone in high-risk endometrial cancer appears to be an oncologically safe technique over a long observational time. Systematic lymphadenectomy in this population does not offer a survival advantage.

Objective In endometrial carcinoma patients, sentinel lymph node bilateral mapping fails in 20-25% of cases, with several factors affecting the likelihood of detection. However, pooled data about predictive factors of failure are lacking. The aim of this systematic review and meta-analysis was to assess the predictive factors of sentinel lymph node failed mapping in endometrial cancer patients undergoing sentinel lymph node biopsy. Methods A systematic review and a meta-analysis was performed searching all studies assessing predictive factors of sentinel lymph node failed mapping in apparent uterine-confined endometrial cancer patients undergoing sentinel lymph node biopsy through the cervical injection of indocyanine green. The associations between sentinel lymph node failed mapping and predictive factors of failure were assessed, calculating the odds ratio (OR) with 95% confidence intervals. Results Six studies with a total of 1345 patients were included. Compared with patients with sentinel lymph node bilateral successful mapping, patients with sentinel lymph node failed mapping showed: OR 1.39 (p=0.41) for body mass index >30 kg/m 2; OR 1.72 (p=0.24) for menopausal status; OR 1.19 (p=0.74) for adenomyosis; OR 0.86 (p=0.55) for prior pelvic surgery; OR 2.38 (p=0.26) for prior cervical surgery; OR 0.96 (p=0.89) for prior Cesarean section; OR 1.39 (p=0.70) for lysis of adhesions during surgery before sentinel lymph node biopsy; OR 1.77 (p=0.02) for indocyanine green dose <3 mL; OR 1.28 (p=0.31) for deep myometrial invasion; OR 1.21 (p=0.42) for International Federation of Gynecology and Obstetrics (FIGO) grade 3; OR 1.89 (p=0.01) for FIGO stages III-IV; OR 1.62 (p=0.07) for non-endometrioid histotype; OR 1.29 (p=0.25) for lymph-vascular space invasion; OR 4.11 (p<0.0001) for enlarged lymph nodes; and OR 1.71 (p=0.022) for lymph node involvement. Conclusion Indocyanine green dose <3 mL, FIGO stage III-IV, enlarged lymph nodes, and lymph node involvement

Objective Next-generation sequencing (NGS) analysis has become an essential tool for endometrial carcinoma management. Moreover, molecular-driven therapies play an increasingly remarkable role in the era of precision oncology. This study aims to determine the clinical relevance of NGS testing in endometrial carcinoma management by analyzing the clinical benefit of NGS-driven targeted therapies. Methods A single-center retrospective study was conducted on 25 endometrial carcinoma patients who underwent Foundation Medicine CDx assay at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS (Rome, Italy). Tumor samples were analyzed by Foundation One CDx. A descriptive analysis of tumor genome profiles was performed. Assessment of clinical benefit according to RECIST 1.1 criteria was analyzed for patients who received a tailored treatment according to actionable targets identified by NGS testing. Results Out of 25 endometrial carcinoma patients, 11 received targeted therapy. One patient was excluded from the clinical benefit assessment because of COVID-19-related death 1 month after starting the treatment. Eight of the remaining 10 patients benefited from targeted therapies, with an overall clinical benefit rate of 80%. A targeted agent belonging to the PI3K pathway was given to seven patients, with evidence of three partial responses (42.9%), three stable diseases (42.9%), and one progressive disease (14.2%) according to RECIST 1.1 criteria. One complete response (33.3%), one stable disease (33.3%), and one progressive disease (33.3%) were observed in the three patients treated with poly(ADP-ribose) polymerase (PARP) inhibitors according to their homologous recombination deficiency (HRD) status. Conclusion This study highlights the importance of characterizing the mutation profile of patient tumors through NGS. Our findings suggest a clinical benefit of using NGS-driven targeted therapies in endometrial carcinoma patients. However, this personalized approach cou

ObjectiveTo analyze the clinicopathological features and outcomes in patients with endometrial cancer with isolated lymphatic recurrence after lymphadenectomy, stratified by different isolated lymphatic recurrence sites and treatment approaches. MethodsWe retrospectively reviewed all surgically treated patients with endometrial cancer, identifying those with recurrence. We defined primary isolated lymphatic recurrence as the first and unique evidence of recurrence in lymph node-bearing areas, without concomitant vaginal, hematogenous, or peritoneal recurrence. Isolated lymphatic recurrences were classified as pelvic, para-aortic, distant, or multiple sites. Our primary outcome was cause-specific survival after diagnosis of the recurrence. ResultsAmong 4216 patients with surgically staged endometrial cancer, we identified 66 (1.6%) women with isolated lymphatic recurrence. The overall median cause-specific survival for patients with isolated lymphatic recurrence was 24 months. Although cause-specific survival was not significantly different between the four isolated lymphatic recurrence groups (p=0.21), 7 of 15 (47%) patients with isolated lymphatic recurrence in the para-aortic area were long-term survivors. At multivariate Cox regression, the absence of lymphovascular space invasion and grade 1 histology in the primary tumor were significantly associated with improved cause-specific survival. In addition, patients with isolated lymphatic recurrence who underwent surgery for recurrence (with/without other associated therapies) had improved cause-specific survival compared with patients who did not undergo surgery, also after adjusting for age. ConclusionsLow-grade histology and absence of lymphovascular space invasion in the primary tumor were predictors of improved prognosis in patients with endometrial cancer with isolated lymphatic recurrence. In addition, in this retrospective cohort, patients with isolated lymphatic recurrence who were selected for eradicative

Objective: This retrospective observational study aims to evaluate the association between the extent of parametrial invasion (PMI) and disease-free survival (DFS) and cancer-specific survival (CSS) in patients with locally advanced cervical cancer (LACC). Materials and methods: This study included patients with LACC showing parametrial invasion at Magnetic Resonance Imaging (MRI). They were treated with neoadjuvant chemo-radiotherapy (CT/RT) before undergoing radical hysterectomy. The staging MRIs were reviewed retrospectively. Measurements of maximum PMI (PMImax) and parametrial length were taken bilaterally. After that, PMIratio was calculated by dividing PMImax by parametrial length. Analysis was conducted on homogeneous subsets of patients, grouped based on their pathological lymph nodal evaluation (N- and N+). Correlations between PMImax and PMIratio with DFS and CSS were evaluated in both the N- and N+ groups, employing univariable Cox regression analysis. Results: Out of 221 patients, 126 (57%) had non-metastatic lymph nodes (N-), while 95 (43%) had metastatic lymph nodes (N+). The median observation period for all these patients was 73 months (95% confidence interval [CI]: 66–77). The 5-year DFS and CSS probability rates were 75% and 85.7%, respectively, for the N- group and 54.3% and 73.6%, respectively, for the N+ group. A higher PMImax (hazard ratio [HR] = 1.09) and PMIratio (HR = 1.04) correlated with worse overall survival in patients in the N- group (p = 0.025 and p = 0.042). These parameters did not show a significant statistical association in the N+ group. Conclusions: The degree of PMI evaluated on MRI affects outcome in N- patients with LACC. Clinical relevance statement: The degree of MRI parametrial invasion affects disease-free survival and cancer-specific survival in patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer. This MRI finding can be easily incorporated into routine clini

Endometrial cancer is the most common gynecological malignancy in Europe and its management involves a variety of health professionals. In recent years, big discoveries were made concerning the management of patients diagnosed with endometrial cancer, particularly in the field of molecular biology and minimally invasive surgery. This requires the continuous updating of guidelines and protocols over the years. In this paper, we aim to summarize and compare common points and disparities among protocols for management of patients diagnosed with endometrial cancer by leading international gynecological oncological societies. We therefore systematically report the parallel among the guidelines based on the various steps patients with endometrial cancer usually undergo. The comparison between American and European protocols revealed some relevant disparities, in particular regarding surgical staging, molecular biology application as a prognostic tool and follow up regimens. This could possibly cause differences in interpreting and applying protocols in clinical practice in small centers, leading to a lack of adherence to guidelines or even prompting a confusing mix of them.

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.