Giuseppe Vizzielli

Sentinel lymph node biopsy in apparently early-stage epithelial ovarian cancer: a systematic review and meta-analysis

To evaluate the detection rate, sensitivity, and negative predictive value (NPV) of sentinel lymph node (SLN) biopsy in patients with apparently early-stage epithelial ovarian cancer (EOC). A systematic search of multiple electronic databases was conducted from inception to October 31, 2025. Studies reporting detection rate, sensitivity, and NPV of SLN biopsy in apparently early-stage EOC, with completion pelvic and para-aortic lymphadenectomy as reference standard, were included. Study selection, risk-of-bias assessment, and data extraction were independently performed by four reviewers. Pooled estimates with 95 % confidence intervals (CI) were calculated using random-effects models on a per-patient basis and by anatomical site. Heterogeneity was assessed using the I Fourteen studies comprising 365 patients were included. Most studies used indocyanine green injected into the infundibulopelvic ligament for para-aortic mapping and the utero-ovarian ligament for pelvic mapping. The pooled para-aortic detection rate was 79.9 % (95 %CI 66.1-91.4 %; I In apparently early-stage EOC, SLN biopsy shows acceptable para-aortic detection but limited pelvic detection. Nonetheless, sensitivity and NPV indicate high diagnostic accuracy. Further studies are needed to optimize pelvic mapping strategies and confirm these findings. At present, sentinel lymph node mapping in apparently early-stage epithelial ovarian cancer should be regarded as investigational and not as standard of care.

Exploring PIPAC for managing platinum resistant and refractory ovarian cancer with peritoneal spread: A collaborative multi-institutional study

Platinum-resistant or refractory epithelial ovarian cancer (EOC) remains a significant clinical challenge, often leading to rapid progression and poor prognosis. Palliative treatments aimed at improving quality of life are warranted. To assess the feasibility and potential benefits of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in patients with platinum-resistant or refractory EOC. Prospective multicenter observational study (2016-2023). feasibility, defined as completion of ≥3 planned PIPAC cycles within 120 days without ≥ grade 3 treatment related adverse events (CTCAE v5.0). Secondary endpoints: safety; disease control (RECIST 1.1); changes in Peritoneal Cancer Index and Fagotti score; ascites control; CA-125 response; conversion to cytoreductive surgery (±HIPEC); and overall survival (OS). Forty patients were enrolled. Ninety-seven percent of procedures were completed. Feasibility was 65.0 % (26/40; 95 % CI 49.51-77.87); no grade ≥3 events occurred. Key secondary outcomes included a clinical benefit rate of 35 % in the intention-to-treat (ITT) population and 53.8 % in the per-protocol (PP) population, median time to ascites resolution of one cycle, and median overall survival of 14 months (17 months in PP). Higher white blood cell count and ascites volume were significantly associated with progression (p = 0.035 and p = 0.025). Three platinum-refractory patients became eligible for surgery, two underwent optimal cytoreduction. Median OS was 14 months (17 months in PP). A non-significant trend toward longer OS was observed in platinum-refractory versus platinum-resistant disease (18 vs 9 months; p = 0.093). PIPAC is a feasible, well-tolerated option in platinum-resistant and refractory EOC with potential to stabilize disease, relieve ascites and enable surgery in selected cases.

Circulating tumor DNA in the diagnosis of ovarian cancer: a systematic review

Ovarian cancer remains a leading cause of gynecologic cancer mortality worldwide, largely due to late-stage diagnosis and limited early detection tools. Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive biomarker with the potential to improve diagnostic accuracy through detection of tumor-specific genetic and epigenetic alterations. This systematic review aimed to evaluate the diagnostic accuracy of ctDNA in detecting ovarian cancer compared to healthy controls or benign conditions. A comprehensive literature search was conducted across PubMed, Web of Science, and EBSCO databases through April 2024, including studies that assessed sensitivity, specificity of ctDNA assays in plasma or serum samples. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. PROSPERO registration number: CRD42024590089. Nineteen studies met inclusion criteria, employing a variety of molecular techniques including polymerase chain reaction-based methylation assays (73.7%) and sequencing methods (whole genome sequencing/next-generation sequencing) (21%), targeting single genes or multi-gene panels. Diagnostic accuracy of ctDNA varied, with sensitivity (40.6%-94.7%) and specificity (56%-100%) ranging broadly, but often outperforming CA125, particularly in early-stage. Concordance between ctDNA and tumor tissue ranged from moderate (r = 0.428) to strong (r = 0.771). Although heterogeneity across studies precluded meta-analysis, narrative synthesis suggests that ctDNA may offer an improved early detection capability over CA125, through methylation and copy number variation analyses. Further controlled prospective studies are needed to validate the clinical utility of ctDNA as a complementary tool in ovarian cancer detection.

The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights

Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, which represents an interplay between external agents and internal genitalia, and its potential profiling role in early detection beyond the promise of microbiota-targeted therapies. Objectives: This review aims to assess whether such a correlation is speculative or scientifically grounded. Methods: A focused literature search was conducted on vaginal microbiota and its correlation with ovarian cancer to define the current state of knowledge. Results: Mixed outcomes have been reported, yet there is a rational and scientific basis supporting further investigation. Clinical approaches increasingly consider vaginal microbiota as relevant. However, we have to say that most available evidence is still preliminary and largely preclinical to set realistic expectations for readers. Although additional studies are needed, emerging insights highlight its importance and practical implications. We present a diagnostic–therapeutic management flowchart summarizing current evidence). Discussion: Most links between the vaginal microbiota and ovarian cancer are correlational rather than causal. The idea that microbes ascend from the vagina to the ovaries is proposed but still definitely not demonstrated. Confounding factors like age, hormones, and BRCA status complicate interpretation, and ovarian cancer itself could secondarily alter the microbiota. Mechanistic studies and longitudinal data are still needed to clarify whether dysbiosis contributes to carcinogenesis or is merely a consequence. As gynecologists, we summarize key aspects and emphasize to colleagues the importance of incorporating these findings into daily clinical practice. Vaginal dysbiosis should be considered not only a local imbalance but also a potential strategy for primary cancer prevention. Conclusions: Future research on the tumor microenvironment and vaginal microbiota will expand scientific knowledge and guide innovative preventive and therapeutic strategies.

Surgical timing in advanced ovarian cancer during the TRUST trial era: A systematic review, meta-analysis and study-level meta-regression of randomized controlled trials

The best surgical timing for advanced epithelial ovarian cancer, whether primary debulking surgery or interval debulking surgery, remains debated. Recent data, including the preliminary ones from TRUST trial, necessitates an updated critical evaluation. A systematic search of PubMed identified only randomized controlled trials comparing interval debulking surgery versus primary debulking surgery in patients with newly diagnosed advanced ovarian cancer. Primary outcomes included overall survival (OS) and progression-free survival (PFS). A random-effects meta-analysis, meta-regression, cumulative synthesis, and leave-one-out influence analysis were performed. A total of 2303 patients were included. Compared to primary debulking surgery, interval debulking surgery was associated with lower rates of postoperative complications (OR = 0.37; 95 % CI: 0.18-0.79; P = 0.01) and mortality (OR = 0.23; 95 % CI: 0.09-0.57; P = 0.002). Meta-analysis showed higher rates of complete cytoreduction with interval debulking surgery (OR = 3.84; 95 % CI: 2.14-6.91; P < 0.00001) and lower rates of macroscopic residual disease (OR = 0.20; 95 % CI: 0.13-0.30; P < 0.00001). Pooled data revealed no significant difference in OS (HR = 0.95; 95 % CI: 0.87-1.04; P = 0.26) or PFS (HR = 0.94; 95 % CI: 0.85-1.03; P = 0.16). Subgroup analyses by stage and residual disease confirmed similar survival outcomes. The meta-regression results suggested that even in trials with very high complete cytoreduction rates, no clinically meaningful OS benefit was observed for upfront surgery. In conclusion, interval debulking surgery offers comparable survival outcomes to primary debulking, with reduced perioperative morbidity and mortality, supporting its role as a valid surgical alternative. PROSPERO REGISTRATION NUMBER: CRD420251105308.

Inflammatory Indices and CA 125: A New Approach to Distinguish Ovarian Carcinoma and Borderline Tumors in Suspicious Ovarian Neoplasms from a Retrospective Observational Multicentric Study

Background and Objectives: This study aimed to evaluate the diagnostic potential of systemic inflammatory indices such as Systemic Inflammation Response Index (SIRI) and Systemic Inflammatory Response (SIR). These were assessed in combination with CA 125 to distinguish ovarian carcinoma (OC) from borderline ovarian tumors (BOT) in patients with suspicious adnexal masses. Materials and Methods: A retrospective multicenter observational study including patients undergoing surgery for suspected ovarian neoplasms was conducted. Inclusion criteria required preoperative blood sampling for inflammatory markers and CA 125. SIR-125 and SIRI-125 were developed by combining SIR and SIRI with CA 125 levels. Diagnostic performance was assessed using ROC curve analysis and linear regression models. Results: A total of 63 patients (42 BOT, 21 OC) were analyzed. OC patients exhibited significantly higher SIR-125 and SIRI-125 values (p &lt; 0.001). ROC analysis demonstrated good diagnostic accuracy, with AUCs of 0.83 (SIR-125) and 0.82 (SIRI-125). SIR-125 showed higher specificity (0.83), while SIRI-125 had superior sensitivity (0.86). Conclusions: SIR-125 and SIRI-125 enhance diagnostic differentiation between OC and BOT, providing a simple, cost-effective preoperative tool. Future prospective studies are needed to validate these findings in broader patient populations.

Cytoreductive Surgery Plus HIPEC in Recurrent or Newly Diagnosed Advanced Epithelial Ovarian Cancer: a Meta-analysis

Abstract Background In 2024, two randomized controlled trials (RCTs) were published, providing new high-quality evidence on HIPEC in epithelial ovarian cancer (EOC). Updating data on progression-free survival (PFS) and adverse events could offer a clearer understanding of the benefits and risks of HIPEC combined with cytoreductive surgery (CRS), with or without prior neoadjuvant chemotherapy (NACT). Patients and Methods An electronic search was conducted using PubMed, Web of Science, EBSCO, and CENTRAL up to 23 November 2024. We only included RCTs reporting PFS and adverse events of interval or secondary CRS, with or without HIPEC, in newly diagnosed or recurrent EOC. Results The meta-analysis included six RCTs. The addition of HIPEC to surgery significantly improved PFS in patients with newly diagnosed advanced-stage EOC who received NACT (HR 0.59; 95% CI 0.39–0.88; p = 0.01). No significant difference in PFS was observed between secondary CRS plus HIPEC and CRS alone in recurrent ovarian cancer without prior NACT (HR 1.22; 95% CI 0.82–1.83; p = 0.32). Regarding adverse events, a decrease in platelet count of any grade was more frequent in the HIPEC group (p = 0.03). The overall risk of acute kidney failure (AKF) was 10.6%, with a significantly higher incidence compared with CRS alone (p = 0.003). Conclusions The addition of HIPEC to CRS significantly improved PFS compared with surgery alone in patients with advanced EOC who received NACT. However, the treatment was associated with a higher incidence of AKF, which occurred in 10.6% of patients who underwent HIPEC.

Chemoembolization, Radioembolization, and Percutaneous Ablation: New Opportunities for Treating Ovarian Cancer Liver Metastasis

Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5 cm or up to 3 tumors smaller than 3 cm and tumors 1 cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

Correspondence on ‘Sentinel lymph node assessment in patients with atypical endometrial hyperplasia: a systematic review and meta-analysis’ by Vieira-Serna et al

Sentinel node mapping in high-intermediate and high-risk endometrial cancer: Analysis of 5-year oncologic outcomes

To assess 5-year oncologic outcomes of apparent early-stage high-intermediate and high-risk endometrial cancer undergoing sentinel node mapping versus systematic lymphadenectomy. This is a multi-institutional retrospective, propensity-matched study evaluating data of high-intermediate and high-risk endometrial cancer (according to ESGO/ESTRO/ESP guidelines) undergoing sentinel node mapping versus systematic pelvic lymphadenectomy (with and without para-aortic lymphadenectomy). Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard methods. Overall, the charts of 242 patients with high-intermediate and high-risk endometrial cancer were retrieved. Data on 73 (30.1%) patients undergoing hysterectomy plus sentinel node mapping were analyzed. Forty-two (57.5%) and 31 (42.5%) patients were classified in the high-intermediate and high-risk groups, respectively. Unilateral sentinel node mapping was achieved in all patients. Bilateral mapping was achieved in 67 (91.7%) patients. Three (4.1%) patients had site-specific lymphadenectomy (two pelvic areas only and one pelvic plus para-aortic area), while adjunctive nodal dissection was omitted in the hemipelvis of the other three (4.1%) patients. Sentinel nodes were detected in the para-aortic area in eight (10.9%) patients. Twenty-four (32.8%) patients were diagnosed with nodal disease. A propensity-score matching was used to compare the aforementioned group of patients undergoing sentinel node mapping with a group of patients undergoing lymphadenectomy. Seventy patient pairs were selected (70 having sentinel node mapping vs. 70 having lymphadenectomy). Patients undergoing sentinel node mapping experienced similar 5-year disease-free survival (HR: 1.233; 95%CI: 0.6217 to 2.444; p = 0.547, log-rank test) and 5-year overall survival (HR: 1.505; 95%CI: 0.6752 to 3.355; p = 0.256, log-rank test) than patients undergoing lymphadenectomy. Sentinel node mapping does not negatively impact 5-year outcomes of high-intermediate and high-risk endometrial cancer. Further prospective studies are warranted.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) Applied to Platinum-Resistant Recurrence of Ovarian Tumor: A Single-Institution Experience (ID: PARROT Trial)

Abstract Background We aimed to investigate the therapeutic efficacy and safety of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in platinum-resistant recurrence of ovarian cancer and peritoneal carcinomatosis, while our secondary endpoint was to establish any changes in quality of life estimated via the EORTC QLQ-30 and QLQ-OV28 questionnaires. Methods In this monocentric, single-arm, phase II trial, women were prospectively recruited and every 28–42 days underwent courses of PIPAC with doxorubicin 2.1 mg/m2 followed by cisplatin 10.5 mg/m2 via sequential laparoscopy. Results Overall, 98 PIPAC procedures were performed on 43 women from January 2016 to January 2020; three procedures were aborted due to extensive intra-abdominal adhesions. The clinical benefit rate (CBR) was reached in 82% of women. Three cycles of PIPAC were completed in 18 women (45%), and 13 (32.5%) and 9 (22.5%) patients were subjected to one and two cycles, respectively. During two PIPAC procedures, patients experienced an intraoperative intestinal perforation. There were no treatment-related deaths. Nineteen patients showed no response according to the Peritoneal Regression Grading Score (PRGS) and 8 patients showed minor response according to the PRGS. Median time from ovarian cancer relapse to disease progression was 12 months (95% confidence interval [CI] 6.483–17.517), while the median overall survival was 27 months (95% CI 20.337–33.663). The EORTC QLQ-28 and EORTC QLQ-30 scores did not worsen during therapy. Conclusions PIPAC seems a feasible approach for the treatment of this subset of patients, without any impact on their quality of life. Since this study had a small sample size and a single-center design, future research is mandatory, such as its application in addition to systemic chemotherapy.

ASO Author Reflections: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Platinum-Resistance Ovarian Cancer Patients

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review

PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.

Sentinel-node biopsy in apparent early stage ovarian cancer: final results of a prospective multicentre study (SELLY)

To evaluate the sensitivity and specificity of sentinel-lymph-node mapping compared with the gold standard of systematic lymphadenectomy in detecting lymph node metastasis in apparent early stage ovarian cancer. Multicenter, prospective, phase II trial, conducted in seven centers from March 2018 to July 2022. Patients with presumed stage I-II epithelial ovarian cancer planned for surgical staging were eligible. Patients received injection of indocyanine green in the infundibulo-pelvic and, when feasible, utero-ovarian ligaments and sentinel lymph node biopsy followed by pelvic and para-aortic lymphadenectomy was performed. Histopathological examination of all nodes was performed including ultra-staging protocol for the sentinel lymph node. 174 patients were enrolled and 169 (97.1 %) received study interventions. 99 (58.6 %) patients had successful mapping of at least one sentinel lymph node and 15 (15.1 %) of them had positive nodes. Of these, 11 of 15 (73.3 %) had a correct identification of the disease in the sentinel lymph node; 7 of 11 (63.6 %) required ultra-staging protocol to detect nodal metastasis. Four (26.7 %) patients with node-positive disease had a negative sentinel-lymph-node (sensitivity 73.3 % and specificity 100.0 %). In a multicenter setting, identifying sentinel-lymph nodes in apparent early stage epithelial ovarian cancer did not reach the expected sensitivity: 1 of 4 patients might have metastatic lymphatic disease unrecognized by sentinel-lymph-node biopsy. Nevertheless, 35.0 % of node positive patients was identified only thanks to ultra-staging protocol on sentinel-lymph-nodes.

Characteristics and outcomes of surgically staged multiple classifier endometrial cancer

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. 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. 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). 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.

Fertility-Sparing Treatments in Endometrial Cancer: A Comprehensive Review on Efficacy, Oncological Outcomes, and Reproductive Potential

Endometrial cancer (EC) affects 3–14% of women under 40 who wish to preserve their fertility. The standard treatment for EC is a hysterectomy with salpingo-oophorectomy. However, for those desiring fertility preservation, oral progestogens such as medroxy-progesterone acetate (MPA) or megestrol acetate (MA) are the most common therapies in Fertility-Sparing Treatment (FST). Other treatments include gonadotropin-releasing hormone agonist (GnRHa), levonorgestrel-releasing intrauterine system (LNG-IUS), and metformin plus progestin. This comprehensive review evaluates the best FST options for women with reproductive potential. PubMed, EMBASE, and Scopus were searched in June 2023 using specific keywords. Studies included in the review focused on patients with EC undergoing FST, with outcomes such as complete response rate (CRR), recurrence rate (RR), pregnancy rate (PR), and live birth rate. Eighteen studies met the inclusion criteria, involving 23,976 patients. In only-oral progestin trials, CRR ranged from 18% to 100%; RR ranged from 0% to 81.8%; Death Rate ranged from 0% to 3.6%. In studies combining oral progestin with LNG-IUS, CRR ranged from 55% to 87.5%; RR ranged from 0% to 41.7%; Death Rate was 0%. Most patients with Stage IA EC received MPA or MA. Fertility-related outcomes were reported in 15 studies. PR ranged from 4 to 44 patients in trials involving only oral progestins. When combining oral progestin with LNG-IUS, PR ranged from 1 to 46 patients. Progestin therapy, including oral MPA and MA, is considered safe and effective, with limited evidence supporting the use of LNG-IUS.

Robotic single-port (da Vinci SP) versus multiport (da Vinci Xi) for the treatment of atypical endometrial hyperplasia and endometrial cancer: A multi-institutional comparison of surgical outcomes

The da Vinci SP robotic platform offers a novel single-port approach for minimally invasive surgery. Despite its potential, data on its safety and performance in gynecologic oncology remain limited. We aimed to compare surgical outcomes of da Vinci SP versus da Vinci Xi systems in the staging of endometrial cancer (EC). This is a multi-institutional study. Data of consecutive patients with apparent early-stage EC or atypical endometrial hyperplasia who underwent robotic surgery between January 2023-March 2025 were collected. The primary outcome was to compare the surgical outcomes between da Vinci SP and da Vinci Xi. A total of 189 patients were included: 97 (51.3 %) underwent SP surgery and 92 (48.7 %) Xi. The median (range) of operative time, estimated blood loss, and postoperative hospital stay were comparable for SP and Xi groups (140 [70-296] vs. 143 [60-297] min, p = 0.66, 40 [0-250] vs. 64 [0-1300] mL, p = 0.12, 3 [1-11] vs. 3[1-10] days, p = 1). Docking time was significantly shorter in the SP group (10 [4-31] vs. 12 [7-30] min for SP and Xi, respectively, p = 0.004). Intraoperative or post-operative complications rates were comparable (p = 0.30 and p = 0.14,respectively). The patient-reported pain score was significantly lower at 12h and 24h in the Xi group (p = 0.001), while was comparable at 48h after surgery (p = 1). The da Vinci SP system appears to be non-inferior to the multiport da Vinci Xi for surgical staging of early-stage EC. Comparable perioperative outcomes support its clinical use, although patient selection criteria and long-term results require further investigation.

Survival and perioperative outcomes of pelvic exenteration in primary advanced and recurrent endometrial carcinoma: A systematic review and meta-analysis

To assess survival and perioperative complications and mortality of pelvic exenteration (PE) in recurrent and advanced endometrial carcinoma (EC) patients. A systematic review and a meta-analysis was performed searching 7 electronic databases from their inception to May 2024 for all peer-reviewed studies that reported as a study outcome at least the 5 years-overall survival (OS) of PE in recurrent and/or advanced EC patients. Our outcomes were 5 year-OS from PE as primary outcome, and all extractable outcomes about PE survival [overall OS, 5 year- and overall disease specific survival (DSS), 5 year- and overall progression free survival (PFS)] and perioperative mortality and complications. Rates of survival outcomes and perioperative mortality and complications were calculated as individual and pooled estimates, with 95 % confidence intervals (CI). Subgroup analyses were planned for all study outcomes based on recurrent or advanced EC, separately. 6 studies with 166 patients were included. In women underwent PE for advanced or recurrent EC, pooled rate was: 41.7 % (95 % CI: 25.6-57.8 %) for 5 year-OS; 30.4 % (95 % CI: 14.9-45.8 %) for 5 year-DSS; 26.6 % (95 % CI: 10.6-42.5 %) for overall DSS; 51.8 % (95 % CI: 25.6-78.0 %) for 5 year-PFS; 9.7 % (95 % CI: 5.7-16.1 %) for perioperative mortality; 56.1 % (95 % CI: 32.3-76.4 %) for perioperative complications. Subgroup analyses were suitable exclusively in the "recurrent EC" subgroup and showed even worsened outcomes. In women with advanced or recurrent EC, PE shows not encouraging survival outcomes, with relatively high rates of perioperative mortality and complications. These outcomes further worsened in the subgroup of only recurrent EC. However, they should be confirmed by more updated studies.

One‐Step Nucleic Acid Amplification Analysis of Sentinel Lymphatic Nodes in Endometrial Cancer Patients ( EU ‐ OSNA ): A European Multicenter Diagnostic Accuracy Study

ABSTRACT Objective This European multicenter study aimed to assess the diagnostic accuracy of one‐step nucleic acid amplification (OSNA) as the primary endpoint by comparing this method with ultrastaging for the detection of sentinel node metastases in endometrial cancer patients. Methods European multicenter prospective performance study including data from 10 centers across 5 European countries. Each node, upon removal of surrounding adipose tissue, was sliced in 2 mm thick sections and equally distributed between ultrastaging and OSNA. OSNA is based on cytokeratin‐19 detection, serving as a metastatic marker. Sensitivity, specificity, and concordance of OSNA versus ultrastaging were calculated at nodal and patient levels. Results Seven hundred forty‐three sentinel nodes from 366 patients were evaluated. Compared to ultrastaging, OSNA showed concordance, specificity, and sensitivity of 95%, 97.6%, and 41.2% at the nodal level and 93.2%, 96.2%, and 47.8% at the patient level, respectively. In reverse analysis, when compared to OSNA, the ultrastaging showed a sensitivity of 45.2% and 45.8% at the nodal and patient levels, respectively. Irrespective of the size of metastasis, both methods agreed in 14 positive and 692 negative nodes (95%). This resulted in 24 (6.56%) patients with a positive OSNA and 23 (6.28%) patients with a positive ultrastaging finding. The number of discordant nodes was 47 (6.33%), 40 (85.1%) of them were micrometastases. Benign epithelial inclusions occurred in 4 nodes (0.54%) and 4 patients (1.09%). Conclusion Compared with ultrastaging, OSNA showed high concordance and specificity, but sensitivity was low—similar to ultrastaging compared with OSNA as an index test in reverse analysis. The main limitation in comparing the two approaches by splitting the sentinel nodes was the tissue allocation bias. As reflected in the number of discordant cases, especially at the micrometastases level. The distribution of patients with node metastases was comparable between the two methods at both the nodal and patient levels. Trial Registration German Clinical Trial Register: Nr. DRKS00021520

Fertility-sparing management of low-grade endometrial stromal sarcoma: A systematic review of oncologic and reproductive outcomes

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare malignancy and the standard of care, precludes future childbearing. Although fertility-sparing treatment (FST) may be considered in carefully selected patients, high-quality evidence regarding its efficacy and safety is limited. This review aims to systematically evaluate the oncologic and reproductive outcomes associated with conservative treatment for LG-ESS. Pubmed Database, Scopus Database and Embase Database were screened in September 2024 from the first publication about women with LG-ESS treated with a surgical FST. We included the studies containing data about oncologic, and reproductive outcomes. This study adheres to PRISMA guidelines and is registered with PROSPERO (CRD42024605140). The quality of the studies was assessed using the Newcastle-Ottawa scale. 9 studies fulfilled inclusion criteria, and 89 patients were analyzed. Recurrence was observed in 51 out of 89 patients (57.3 %) with a mean recurrence-free interval ranging between 3 and 40.5 months. A mortality rate of 1.1 % was observed, with a mean follow-up duration ranging from 38.5 to 84.5 months. The overall pregnancy rate was 41.5 % and the live birth rate was 78.1 %. The preterm delivery rate was 8 % and 3.9 % of patients required assisted reproduction technology. Considering the limitations of the available evidence, FST in women with LG-ESS carries a relatively high risk of tumor relapse, though it does not increase the risk of death. Fertility outcomes seem to be encouraging. Resection of the malignant uterine lesion combined with adjuvant hormonal treatment may be considered for selected early-stage patients, with close follow-up.

Detection rate of sentinel lymph nodes in early-stage endometrial cancer according to age

Sentinel lymph node (SNL) mapping plays a crucial role in staging patients with an apparent early-stage endometrial cancer. Older age may be associated with lower detection rates due to factors such as decreased lymphatic flow; but consensus is lacking. This study aims to evaluate the impact of age on the SNL detection rate in patients undergoing minimally invasive surgical staging for endometrial cancer. This multicenter retrospective study included apparent early-stage endometrial cancer patients undergoing minimally invasive surgical staging, including SLN mapping across four ESGO-accredited centers (2020-2023). Patients were categorized into two age groups: <65 years, defined as younger adults and ≥65 years, defined as older adults. Univariate and multivariate logistic regression models were used to identify predictors of bilateral mapping. Overall, 642 patients were identified: 342 (53.3%) patients were classified as younger adults and 300 (46.7%) as older adults. The overall bilateral SLN detection rate was 89.3%, with no or unilateral detection in 10.7% of patients. Older adults had a significantly lower bilateral detection rate than younger adults (85.0% vs. 93.0%, p = 0.005). Multivariate analysis identified age ≥65 years as the only independent predictor of failed bilateral mapping (OR 2.2, 95 % CI 1.3-3.8, p = 0.003). Other clinical, surgical, and pathological factors were not associated with mapping failure. Age ≥65 is independently associated with decreased bilateral SLN detection in early-stage endometrial cancer. Nevertheless, SLN biopsy remains a feasible and reliable staging method in older adults when performed using standardized techniques by experienced surgeons.

Is there a role for the sentinel lymph node in endometrial atypical hyperplasia? Insights from an ESGO-accredited Institution

This study investigates the outcomes of patients with premalignant endometrial findings on biopsy who underwent hysterectomy with sentinel lymph node (SLN) excision and were subsequently diagnosed with endometrial cancer (EC). It aims to highlight the role of nodal assessment in guiding postoperative treatment strategies. Additionally, the study compares surgery complication rates between patients who underwent SLN mapping and those who did not. This retrospective, observational, single-center study was conducted at Udine Hospital between April 2021 and July 2024. 63 patients diagnosed with atypical hyperplasia on endometrial biopsy who underwent hysterectomy and bilateral salpingo-oophorectomy, with or without SLN mapping, were included. All procedures were performed using minimally invasive surgery. Of the 63 patients, 35 (55.6 %) had confirmed atypical hyperplasia on uterine pathology, while 23 (36.5 %) were diagnosed with EC on final pathology. Of the patients who underwent SLN mapping, 18 (43 %) received a final diagnosis of EC and were accurately staged and treated accordingly. In contrast, within the group of patients treated without SLN mapping, 5 (24 %) were diagnosed with EC on final pathology and didn't receive proper staging. No nodal metastases were found in both groups. There was no statistically significant difference in operating time and complication rates between the two groups (with or without SLN mapping), further supporting the procedure's safety. This study's findings underscore the significance of incorporating SLN mapping into hysterectomy and bilateral salpingo-oophorectomy for patients with atypical hyperplasia. This approach enhances accurate staging for patients diagnosed with endometrial cancer on final pathology.

Impact of optimal secondary cytoreductive surgery on survival outcomes in women with recurrent endometrial carcinoma: A systematic review and meta‐analysis

AbstractBackgroundManagement of recurrent endometrial carcinoma (EC) represents a challenge. Although a complete resection of visible disease at secondary surgery (R0) is recommended, the impact of R0 on survival outcomes is unclear and pooled data are lacking.ObjectiveTo quantitatively assess the impact of R0 on survival outcomes in women with EC recurrence.Search StrategyA systematic review and meta‐analysis was performed searching eight electronic databases from their inception up to January 2024.Selection CriteriaAll peer‐reviewed studies that assessed quantitatively the impact of R0 on survival outcomes in women at first EC recurrence were included.Data Collection and AnalysisHazard ratio (HR) with 95% confidence interval (CI) for death of any cause and secondary recurrent or progressive disease in women with EC recurrence who underwent R0 compared to non‐optimal secondary surgical cytoreduction (R1) were pooled and assessed at both univariable and multivariable analyses.Main ResultsThree studies with 442 patients were included. At univariate analysis, in women with EC recurrence and R0 compared to women with EC recurrence and R1, pooled HR was 0.451 (95% CI: 0.319–0.638) for death from any cause, and 0.517 (95% CI: 0.298–0.895; p = 0.019) for recurrent or progressive disease.At multivariate analysis, in women with EC recurrence and R0 compared to women with EC recurrence and R1, pooled HR was 0.447 (95% CI: 0.255–0.783; p = 0.005) for death from any cause, and 0.585 (95% CI: 0.359–0.952; p = 0.031) for recurrent or progressive disease.ConclusionIn women with EC recurrence, R0 is an independent prognostic factor, decreasing the risk of death from any cause by approximatively 55%, and of recurrent or progressive disease by approximatively 40%, compared to R1.

Short- and long-term outcomes of vaginal, laparoscopic, and robotic-assisted surgery in “oldest old” endometrial cancer

To assess the safety and long-term effectiveness of minimally invasive approach in managing "oldest old" endometrial cancer patients. This is a retrospective cohort, multi-institutional study. Consecutive patients, treated between 2000 and 2020, with apparent early-stage endometrial cancer patients, aged ≥85 years. Surgery-related outcomes of robotic-assisted, laparoscopic, and vaginal surgery were compared. Survival was evaluated in patients with at least 3-year follow-up data. Charts of 82 endometrial cancer patients "oldest old" were retrieved. Intermediate-high and high-risk endometrial cancer patients accounted for 26 (31.7 %) and 17 (20.7 %), respectively. In total, 12 (15 %), 45 (55 %), and 25 (30 %) patients underwent robotic-assisted, laparoscopic, and vaginal surgery, respectively. Looking at surgery-related outcomes, robotic-assisted surgery correlated with a longer operative time (p < 0.001) and longer length of hospital stay (p = 0.002) in comparison to laparoscopic and vaginal approaches. Overall, seven (8.5 %) conversions from the planned approach occurred. The surgical approach did not influence disease-free survival (p = 0.6061) and overall survival (p = 0.4950). Via multivariate analysis, only serosal/adnexal invasion correlated with the risk of death (HR: 3.752, p = 0.038). All three minimally invasive approaches are safe and effective methods for managing endometrial cancer in the oldest old population. Chronological age, per se, should not be considered a contraindication for receiving minimally invasive surgery.

Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer

The aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC). We enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1-G2, with myometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semi-quantitative way, according to a 3-tiered scoring system in absent, focal and substantial. Among 524 patients, any positive LVSI was found in 57 patients (10.9%) with focal LVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated to higher rate of G2 (p<0.001), myometrial infiltration (p=0.002) and greater tumor dimensions (p=0.014). Patients with substantial LVSI were more likely to receive adjuvant treatment (6.6% vs. 52.6%, p<0.001). The 5-year OS was 99.5% in patients with absent LVSI and 70.6% in those with substantial LVSI (p<0.001). The 5-year disease free survival (DFS) was 93.6% in patients with absent LVSI and 56.5% in those with substantial LVSI (p<0.001). The rate of distant failures increased from 1.8% for absent LVSI to 22.7% for substantial LVSI (p=0.002). In univariate analysis substantial LVSI was the strongest predictor of poor overall survival (hazard ratio [HR]=11.9, p=0.001). Multivariate analysis showed that substantial LVSI was an independent predictive factor of both recurrence (HR=5.88, p=0.001) and distant failure (HR=10.6, p=0.006). Substantial LVSI represents the strongest independent risk factor for decreased survival and distant relapse, indicating a role for potential hematogenous dissemination.

Hysterectomy alone vs. hysterectomy plus sentinel node mapping in endometrial cancer: Perioperative and long-term results from a propensity-score based study

To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients. This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers. 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. 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.

Mesonephric-Like Adenocarcinomas a Rare Tumor: The Importance of Diagnosis

Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisation’s recent 2020 classification of female genital cancers. The pathogenesis of MLA is unknown and it remains debated whether they represent mesonephric carcinomas (Wolffian) arising in the endometrium/ovary or endometrioid carcinomas (Müllerian) closely mimicking mesonephric carcinomas. Here we report the case of a 57-year-old woman with an initial misdiagnosis of endometrioid adenocarcinoma on diagnostic biopsy. The patient came to our clinical evaluation for the appearance of menometrorrhagia complicated by anemia for several months. Therefore, she underwent pelvic echo-flowmetry, with indication for diagnostic hysteroscopy with endometrial biopsy, which yielded a positive result for endometrioid endometrial adenocarcinoma. Following staging CT scan and targeted examinations on pulmonary findings, the patient underwent surgery with surprise of definitive diagnosis deponent for endometrial MLA. Our intention is to establish a brief review of the scientific evidence in the literature and the tools available for a correct histological diagnosis, in the light of the scant anatomopathological evidence. Our question gives rise to the motive for the publication: is immunohistochemistry the right way to resolve the diagnostic error at histology, which is usually the only source of diagnostic certainty? This case is intended to alert of diagnostic error that risked having the patient treated as a neoplasm with a favorable prognosis and low degree of aggressiveness instead of for a very aggressive and poor prognosis tumor such as MLA.

Influence of uterine manipulator on oncological outcome in minimally invasive surgery of endometrial cancer: A systematic review and meta-analysis

The endoscopic approach for early-stage endometrial cancer (EC) treatment is considered gold standard. Some authors expressed their concern regarding uterine manipulator (UM) as a risk factor for tumor spillage and dissemination allowing peritoneal or lympho-vascular spaces invasion (LVSI). This meta-analysis aimed to evaluate the effect of UM on the presence of LVSI, recurrence rate and presence of atypical or malignant peritoneal cytology in patients with endometrial cancer. We searched electronic databases including PubMed, MEDLINE, Embase, Scopus, EBSCO, Google Scholar, and ClinicalTrials.gov. The pooled results were used to evaluate the association between the use of UM and oncological outcomes. This systematic review was reported according to PRISMA statement 2020. Statistical meta-analysis was performed using Review Manager software. This systematic review included 18 studies (3 prospective studies, 13 retrospective studies, and 2 RCT). The pooled results showed no significant difference (RR: 0.86, 95% CI, 0.69 to 1.08) in the incidence of LVSI between manipulated hysterectomy and total abdominal hysterectomy (TAH) and between UM group and non-UM group in minimally invasive surgery (RR: 1.18, 95% CI, 0.76 to 1.85), no significant difference in the rate of recurrence (RR: 1.11, 95% CI, 0.71 to 1.74), in the incidence of positive peritoneal cytology between manipulated and non-manipulated hysterectomies in minimally invasive surgery (RR: 1.89, 95% CI, 0.74 to 4.83) and before and after the use of uterine manipulator (RR: 1.21, 95% CI, 0.68 to 2.16). We found a positive association between malignant cytology and hysterectomies in which a uterine manipulator had been used in a sub-group analysis where LH/LAVH were compared to TAH. (RR = 2.26, 95% CI, 1.08-4.71. P = 0.03). This meta-analysis supports that the use of uterine manipulator for minimally invasive treatment of endometrial cancer does not increase the rate of recurrence and LVSI. Therefore, the opportunity of any other studies on its use in endometrial cancer women should be questioned.

Clinical impact of surgical energy device (Caiman®) IN elderly patients with Endometrial Cancer (protocol ID: Cineca)

To investigate the clinical performance of the Caiman® energy device in class A radical laparoscopic hysterectomy (RLH) according to Querleu-Morrow classification, combined with bilateral salpingo-oophorectomy (BSO) and pelvic lymph node assessment in elderly patients with early-stage endometrial cancer (EC), specifically focusing on hemostatic effectiveness and safety. Single-institution, prospective observational study. Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Forty-three women over 65 years with FIGO stage IA or IB endometrioid EC were enrolled from September 2021 to August 2023. Use of Caiman® energy device in RLH combined with BSO and pelvic lymph node assessment in elderly patients. The primary endpoint was operative time, with secondary endpoints including perioperative outcomes and postoperative complications. Results demonstrated a median surgical time of 135 min, with no significant intraoperative complications attributed to the Caiman® device. Postoperative complications were minimal, with no severe complications (Grade 4 or 5) and a median hospital stay of two days. The study highlights the advantages of the Caiman® in enhancing surgical efficiency while minimizing risks for elderly patients, suggesting its potential for improving resource allocation and patient outcomes in oncologic surgery. The findings of this study suggest the feasibility of using the Caiman® device for surgical procedures in elderly patients with early-stage endometrial cancer. Future prospective randomized trials are needed to establish its efficacy compared to traditional surgical methods.

The exciting journey of progress: Exploring FIGO 2023 staging for endometrial cancer at a leading ESGO institution

The 2023 FIGO staging of endometrial cancer integrates tumor grade and histology along with molecular features that recognize the prognostic significance of p53 and POLE mutations, accounting for potential conflicts such as lymphovascular space invasion and subserosal invasion. In this single-institution retrospective study, data were collected on 229 endometrial cancer patients from January 2020 to September 2024 and re-stage them according to FIGO 2023 criteria. From FIGO stage 2009 IA, 70 patients do not cross stage (21 are FIGO 2023 IA1 and 49 IA2), 8 patients are upgraded to FIGO IC because of aggressive histotype; 1 is upstaged because of substantial LVSI, and 12 because of aggressive myoinfiltrating tumors (23 % of upstaging). From FIGO 2009 stage IB 34 patients remain in FIGO 2023 IB, while 5 become stage IIB (LVSI) and 27 IIC (aggressive myoinfiltrating), for a total of 32 upstages (48 % of upstaging). Within FIGO 2009 stage II, no proper upstage was possible. We observed a statistical correlation between stages and BMI, as well as between stages and age, for both FIGO 2009 (p = 0.009 and p < 0.001 respectively) and FIGO 2023 (p = 0.002 and p = 0.003 respectively) classifications. Additionally, a correlation was found between tumor grade and BMI (p = 0.02). The FIGO 2023 staging system is gaining importance as recent studies highlight the role of molecular classification in prognosis and personalized therapy. Updating our study's follow-up data will clarify its impact in clinical practice.

Assessment of sentinel Lymph node mapping with different volumes of Indocyanine green in early-stage ENdometrial cancer: the ALIEN study

To evaluate the impact of different volumes of indocyanine green (ICG) on the detection rate and bilateral mapping of sentinel lymph nodes in patients with apparent uterine-confined endometrial cancer. All patients who underwent surgical staging with sentinel node mapping in six reference centers were included. Two different protocols of ICG intracervical injection were used: (1) 2 mL group: total volume of 2 mL injected superficially; (2) 4 mL group: total volume of 4 mL, 2 mL deeply and 2 mL superficially. Logistic regression was used to analyze factors that could influence dye migration and detection rates. A sensitivity analysis was carried out to determine how independent variables could affect the sentinel node detection rate. Of 442 eligible patients, 352 were analyzed (172 in the 2 mL group and 180 in the 4 mL group). The bilateral detection rates of the 2 mL and 4 mL groups were 84.9% and 86.1%, respectively (p=0.76). The overall detection rate was higher with a volume of 4 mL than with 2 mL (97.8% vs 92.4%, respectively; p=0.024). In the univariate analysis the rate of bilateral mapping fell from 87.5% to 73.5% when the International Federation of Gynecology and Obstetrics (FIGO) 2009 tumor stage was >IB (p=0.018). In the multivariate analysis, for both overall and bilateral detection rates a statistically significant difference emerged for the volume of ICG injected and FIGO 2009 stage >IB. Increasing body mass index was associated with worse overall detection rates on univariate analysis (p=0.0006), and significantly decreased from 97% to 91% when the body mass index exceeded 30 kg/m In patients with early-stage endometrial cancer, a volume of 2 mL ICG does not seem to compromise the bilateral detection of sentinel lymph nodes. In women with obesity and FIGO 2009 stage >IB, a 4 mL injection should be preferred.

Study of the Role of the Tumor Microenvironment in Ovarian Cancer ( MICO ): A Prospective Monocentric Trial

ABSTRACT Background Ovarian cancer (OC) is one of the most aggressive tumors requiring new therapeutic approaches. Immunotherapy represents an opportunity, but to date, OC patients do not appear to benefit from current protocols. A better understanding of the composition of the tumor microenvironment (TME), especially in its immune components, could unveil mechanisms of immune suppression in a useful way to predict response to therapies and develop new therapeutic approaches. Method The MICO (tumor MICroenvironment of Ovarian cancer) study is a single‐center observational study. Starting from peritoneal biopsy of high‐grade serous ovarian carcinoma (HGSOC), the purpose of the MICO study is to generate tumor patient‐derived organoid (PDOs) cultures and evaluate the concordance between in vitro platinum‐based chemotherapy sensitivity and in vivo sensitivity. Simultaneously, we will characterize through multiparameter cytofluorimetric analysis the composition of the OC TME, focusing on B lymphocytes and mast cells whose roles in ovarian cancer remain controversial and underinvestigated. Furthermore, patients experiencing recurrence will be longitudinally followed to monitor changes in the TME composition and the responsiveness of PDOs to in vitro stimulation with drugs. Discussion The association between the composition of the TME, the reactivity of the PDOs, and patients' disease progression will be analyzed to identify whether specific subpopulations of tumor‐infiltrating immune cells could be predictive factors of the disease outcomes. The comparison of molecular profiles, in vitro response to drugs, and clinical‐pathological data will allow the definition of a pattern capable of predicting the response of the primary tumor for the identification of those patients who may benefit from specific treatment. Strengths and Limitations The results of our study could help to better understand the OC behavior, may have implications for the development of effective immunotherapy and targeted pharmacological therapies for epithelial OC in a personalized medicine perspective. This will be a monocentric trial with an involvement of only 43 patients, so further studies will need to confirm our results. Trial Registration The clinical trial has been registered at Clinical‐Trials.gov with the identifier NCT06272240 on 02/14/2024

Reproductive, obstetrical and oncological outcomes of fertility-sparing treatment for cervical cancer according to the FIGO 2018 staging system: A systematic review

We assessed reproductive, obstetrical, and oncological outcomes in patients who underwent fertility-sparing treatment by including studies that adhere to the FIGO 2018 staging system. Data on recurrence, mortality, pregnancy rate, live birth rate, and preterm delivery rate were collected. In patients with stages IA1, IA2, and IB1, the recurrence rate was 4.7 % and the death rate was 0.6 %. For patients with stage IB2, the recurrence rate was 12.1 % and the death rate was 3.2 %. Pregnancy rates for conization/simple trachelectomy and radical trachelectomy were 61.7 % and 50 %, respectively. A higher live birth rate (84.4 % vs 58.6 %), and lower preterm birth rate (18.3 % vs 33.3 %) were observed in patients undergoing conization compared to radical trachelectomy. We found a recurrence rate of 4.7 % in patients with stage less than or equal to IB1 and 12.1 % in those with stage IB2. A higher rate of preterm delivery was observed in patients who underwent radical trachelectomy.

Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis

Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of patients with ovarian cancer, a recent systematic review and meta-analysis is lacking. The objective of this study was to determine the association of ctDNA with progression-free-survival and overall survival in patients with epithelial ovarian cancer. An electronic search was conducted using PubMed (MEDLINE), Embase, CENTRAL (Cochrane Library), and CINAHL-Complete from January 2000 to September 15, 2023. To be included in the analysis the studies had to meet the following pre-specified inclusion criteria: (1) evaluable ctDNA; (2) progression-free-survival and overall survival reported as hazard ratio (HR); and (3) the patient population had epithelial ovarian cancer at the time of ctDNA detection. We evaluated the association of ctDNA with progression-free survival and overall survival. Secondary outcomes focused on sub-group analysis of genomic alterations and international Federation of Gynecology and Obstetrics (FIGO) stage. A total of 26 studies reporting on 1696 patients with epithelial ovarian cancer were included. The overall concordance rate between plasma-based and tissue-based analyses was approximately 62%. We found that a high level of ctDNA in epithelial ovarian cancer was associated with worse progression-free survival (HR 5.31, 95% CI 2.14 to 13.17, p<0.001) and overall survival (HR 2.98, 95% CI 1.86 to 4.76, p<0.0001). The sub-group analysis showed a greater than threefold increase in the risk of relapse in patients with positive HOXA9 meth-ctDNA (HR 3.84, 95% CI 1.57 to 9.41, p=0.003). ctDNA was significantly associated with worse progression-free survival and overall survival in patients with epithelial ovarian cancer. Further prospective studies are needed. CRD42023469390.

Early Postoperative Albumin and Neutrophil Dynamics for Risk Stratification After Cytoreductive Surgery in Ovarian Cancer: A Retrospective Multicenter Cohort Study

Background and Objectives: Serum albumin is a widely available and inexpensive biomarker that reflects nutritional status and physiological reserve. Hypoalbuminemia has been linked to poor postoperative outcomes in surgical oncology; however, its role in predicting early complications after cytoreductive surgery for ovarian cancer, as well as the potential contribution of systemic inflammatory indices in nutritionally preserved patients, remains incompletely understood. This study aimed to evaluate the predictive value of early postoperative serum albumin for early surgical complications and to explore whether inflammatory indices could offer additional prognostic information in patients with adequate albumin levels. Materials and Methods: We conducted a retrospective observational cohort study including patients undergoing cytoreductive surgery for ovarian cancer at two Italian tertiary referral centers between July 2023 and December 2025. Postoperative serum albumin was measured on the first postoperative day. Systemic inflammatory parameters were assessed using perioperative changes in neutrophils and composite indices. Early postoperative complications occurring within 30 days were recorded. Multivariable logistic regression analyses were performed, and subgroup analyses were conducted in patients with postoperative albumin ≥3 g/dL. Receiver operating characteristic (ROC) analysis was used to identify an optimal cutoff for significant inflammatory predictors. Results: A total of 121 patients were included, of whom 30 developed early postoperative complications. Patients with complications had significantly lower postoperative albumin levels than those without complications (median 2.75 vs. 3.09 g/dL; p &lt; 0.001). In multivariable analysis, lower postoperative albumin independently predicted early complications (OR 0.26, 95% CI 0.06–0.86). In the subgroup of patients with preserved albumin levels (≥3 g/dL), a smaller postoperative neutrophil decline independently predicted complications (OR 1.56, 95% CI 1.12–2.70). A neutrophil drop cutoff of −1.15 × 103/dL showed good specificity (81.5%) and high negative predictive value (95.7%). Conclusions: Early postoperative serum albumin is a strong predictor of early surgical complications after cytoreductive surgery for ovarian cancer. In patients with preserved nutritional status, dynamic neutrophil changes provide additional prognostic information. Incorporating low-cost metabolic and inflammatory biomarkers may enhance early postoperative risk stratification and support more personalized patient management.

Simple hysterectomy versus radical hysterectomy in early-stage cervical cancer: A systematic review and meta-analysis

This systematic review (SR) and meta-analysis aims to compare the surgery-related results and oncological outcomes between SH and RH in patients with early-stage cervical cancer. We systematically searched databases including PubMed, Embase and Cochrane to collect studies that compared oncological and surgery-related outcomes between SH and RH groups in patients with stage IA2 and IB1 cervical cancer. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. Seven studies comprising 6977 patients were included into our study. For oncological outcomes, we found no statistical difference in recurrence rate [OR = 0.88; 95% CI (0.50, 1.57); P = 0.68] and Overall Survival (OS) [OR = 1.23; 95% CI (0.69, 2.19), P = 0.48]. No difference was detected in the prevalence of positive LVSI and lymph nodes metastasis between the two groups. Concerning surgery-related outcomes, the comprehensive effects revealed that the bladder injury [OR = 0.28; 95% CI (0.08, 0.94), P = 0.04] and bladder disfunction [OR = 0.10; 95% CI (0.02, 0.53), P = 0.007] of the RH group were higher compared to the SH group. This meta-analysis suggested there are no significant differences in terms of both recurrence rate and overall survival among patients with stage IA2-IB1 cervical cancer undergoing SH or RH, while the SH group has better surgery-related outcomes. These data confirm the need to narrow the indication for RH in early-stage cervical cancer.

Scar-Free Laparoscopy in BRCA-Mutated Women

Background and Objectives: BRCA 1 and 2 mutations have a cumulative risk of developing ovarian cancer at 70 years of 41% and 15%, respectively, while a cumulative risk of breast cancer by 80 years of age was 72% for BRCA1 mutation carriers and 69% for BRCA2 mutation carriers. The NCCN recommends risk-reducing salpingo-oophorectomy (RRSO), typically between 35 and 40 years, and upon completion of childbearing in BRCA1 mutation, while it is reasonable to delay RRSO for management of ovarian cancer risk until age 40–45 years in patients with BRCA2. In recent years there have been two main lines of evolution in laparoscopy. The former concerning the development of a single-site laparoscopic and the latter concerning the miniaturisation of laparoscopic instruments (mini/micro-laparoscopy). Materials and Methods: In this case report, we show our experience in prophylactic adnexectomy, on a mutated-BRCA patient, using the MiniLap® percutaneous surgical system. Results: This type of technique is safe and effective and does not require a particular learning curve compared to single-port laparoscopy. Conclusions: The considerable aesthetic advantage of the scars, we believe, albeit to a lesser extent, is useful to find in these patients burdened by an important stress load.

ASO Authors Reflections: Vaginectomy as Surgical Treatment of Recurrent Cervical Cancer

Is a Vaginectomy Enough or is a Pelvic Exenteration Always Required for Surgical Treatment of Recurrent Cervical Cancer? A Propensity-Matched Study

Reporting the perioperative and survival outcomes of vaginectomy with respect to a matched series of pelvic exenteration (PE) in women with isolated recurrent cervical cancer. The records of vaginal recurrent cervical cancer patients admitted at Fondazione Policlinico "Agostino Gemelli" IRCCS in Rome from January 2010 to June 2019 were retrospectively analyzed. A propensity-matched score analysis was performed by age, clinical stage, disease-free interval, and R0 resection. Postsurgical complications and survival rates were evaluated. Fifteen women underwent vaginectomy, and 30 patients were submitted to PE. No statistical differences were observed between the two groups at baseline characteristics. The vaginectomy procedures were successfully performed in all women, and no case required conversion to PE. Moreover, a higher rate of major postoperative complications after PE with respect to vaginectomy (p = 0.027) was recorded. Among them, three women required reoperation within 30 postoperative days, and four experienced two or more complications. Twenty-five (55.6%) women experienced recurrence: 8 of 25 (32.0%) in the vaginectomy group, and 17 of 25 (68%) in the PE group, with a median progression-free survival of 20 months and 13 months, respectively (p = 0.169). In total, 5 of 15 (33.3%) died of disease in the vaginectomy group and 13/30 (43.3%) in the PE group, with a median overall survival of 39 and 18 months for vaginectomy and PE, respectively (p = 0.161). The vaginectomy seems to allow for salvage treatment, such as radiotherapy and/or PE, but with a minimal impact on the quality of life in appropriately selected women with local recurrent cervical cancer.

Predictive factors of surgical complications after pelvic exenteration for gynecological malignancies: a large single-institution experience

To evaluate pre-operative predictors of early (<30 days) severe complications (grade Dindo 3+) in patients with gynecological malignancy submitted to pelvic exenteration (PE). We retrospectively analyzed 129 patients submitted to surgery at Fondazione Policlinico Gemelli between 2010 and 2019. We included patients affected by primary or recurrent/persistent cervical, endometrial, or vulvar/vaginal cancers. Post-operative complications were graded according to the Dindo classification. Logistic regression was used to analyze potential predictors of complications. We performed 63 anterior PE, 10 posterior PE, and 56 total PE. The incidence of early severe post-operative complications was 27.9% (n=36), and the early mortality rate was 2.3% (n=3). More frequent complications were related to the urinary diversion and intestinal surgery. In univariable analysis, hemoglobin ≤10 g/dL (odds ratio [OR]=4.2; 95% confidence interval [CI]=1.65-10.7; p=0.003), low albumin levels (OR=3.9; 95% CI=1.27-12.11; p=0.025), diabetes (OR=4.15; 95% CI=1.22-14.1; p=0.022), 2+ comorbidities at presentation (OR=5.18; 95% CI=1.49-17.93; p=0.012) were predictors of early severe complications. In multivariable analysis, only low hemoglobin and comorbidities at presentation were independent predictors of complications. Pelvic exenteration is an aggressive surgery characterized by a high rate of post-operative complications. Pre-operative assessment of comorbidities and patient health status are crucial to better select the right candidate for this type of surgery.

SLYMEC II study: Overall survival analysis of the impact of LVSI in apparent early stage endometrioid endometrial cancer

In our initial report of the SLYMEC study we published the results evaluated the prognostic impact of substantial lymphovascular space invasion (LVSI) on the sentinel lymph node status and the impact of the different types of LVSI on 3-year disease-free survival. The aim of the SLYMEC II study was to assess the impact of focal and substantial lymphovascular space invasion on 5-years overall survival in the subgroup of patients with endometrioid endometrial cancer. A total of 2030 patients were included in the analysis from the original data set. Focal LVSI were identified in 131 patients (6.4 %), whereas 319 patients (15.7 %) showed substantial LVSI at final pathology. Among 1876 patients who underwent minimally invasive surgery (92.6 %), 442 patents (21.8 %) underwent robotic assisted surgery, whereas and 150 patients (7.6 %) patients underwent open surgery. Rate of overall survival at 5 years was 83.6 % versus 100 % for substantial and focal LVSI groups, respectively (HR for death = 2.1 [95 % CI, 1.4 to 3.2]; P < 0.0001). Patients with endometrioid endometrial cancer having substantial LVSI after surgery showed an increased risk of death in the after 5-years overall survival when compared to patients with negative, or focal LVSI. The presence of positive LVSI in patients with positive sentinel nodes showed a trend toward reduced 5-year overall survival compared to SLN-negative patients, although it did not reach statistical significance.

Proton Beam Therapy in Gynecological Cancers: A Systematic Review of Indications, Complications, and Limitations

Background and Objectives: Gynecological cancers frequently require radiation therapy (RT) in primary, adjuvant, or salvage settings. However, photon-based RT is associated with non-negligible toxicity, and treatment of pelvic recurrences after prior irradiation remains challenging. Proton beam therapy (PBT), due to its favorable dose distribution and reduced exposure of organs at risk (OARs), has emerged as a potential alternative, particularly in re-irradiation scenarios. Despite its expanding use in other malignancies, evidence supporting PBT in gynecologic cancers remains limited. This systematic review aims to investigate the use of PBT in gynecological cancers and its associated complications. Materials and Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO. A comprehensive search (2000–2025) identified studies investigating PBT in gynecologic cancers. Eligible designs included randomized trials and prospective and retrospective series. Reported adverse events were categorized as GI, GU, or other, and only grade ≥3 CT-CAE complications were considered. Results: Of 580 records screened, 9 studies comprising 232 patients met inclusion criteria. Most patients were treated for endometrial (n = 147) or cervical (n = 75) cancer; 90 received chemotherapy. Overall, severe toxicity occurred in 15.2% of patients. GI complications ranged from 0–14% and GU from 0–33%. Complication rates were lowest in adjuvant or de novo treatment series (0–10%), whereas re-irradiation cohorts showed higher rates (up to 33% GU). Comparative studies suggested a possible advantage of PBT over IMRT, particularly for GI toxicity, though data remain limited. Conclusions: Severe GI and GU toxicity after PBT in gynecologic cancers appears infrequent, particularly in primary and adjuvant settings, though re-irradiation remains challenging. Current evidence is restricted to small and heterogeneous studies. Ongoing phase II trials will provide prospective data to clarify feasibility, toxicity, and long-term outcomes. Until then, PBT in gynecologic oncology should be regarded as investigational.

Evaluation of survival and mortality in pelvic exenteration for gynecologic malignancies: a systematic review, meta-analyses, and meta-regression study

Pelvic exenteration is a radical surgery for advanced or recurrent pelvic tumors, requiring careful patient selection and a multi-disciplinary approach. Despite advancements, it remains high-risk, with limited data on outcomes. The present meta-analysis evaluates survival, mortality, and trends to clarify its role in gynecologic oncology. A systematic search was conducted in January 2025 to identify studies on pelvic exenteration outcomes for gynecologic malignancies. Studies with at least 10 patients reporting 5-year overall survival or 30-day mortality were included. Data extracted included patient and surgical characteristics, and a scoring system based on study design, sample size, and center volume was used to include high-quality studies (score ≥3). Poisson regression models were used to analyze the associations between predictors and outcomes, with results expressed as incidence rate ratios and a 95% CI. A total of 46 studies involving 4417 patients met the inclusion criteria. Most patients underwent pelvic exenteration for cervical cancer (N = 3183). Positive pelvic and aortic nodal involvement were key predictors of reduced 5-year overall survival, decreasing by 3.9% and 5.9% per 1% increase in nodal positivity, respectively. Pelvic wall involvement also significantly reduced survival by 15.9%. The 30-day mortality rate was 5.1%, with sepsis (27.2%) being the leading cause of death. Peri-operative mortality decreased significantly over time, with each year of publication associated with a 2.6% decrease in incidence rate. However, pelvic sidewall involvement and total exenteration increased 30-day mortality by 11.5% and 0.7%, respectively. Pelvic exenteration remains a viable but high-risk option for select patients with advanced gynecologic malignancies. Pre-operative assessment and multi-disciplinary planning are essential for optimizing outcomes.

Pelvic exenteration for vulvar cancer: contemporary outcomes from a multinational cohort study

Women with vulvar cancer are considerably older than those with other gynaecological malignancies, raising concerns about the tolerability of radical surgery. Yet, for locally advanced or recurrent disease, pelvic exenteration may be the only curative option. Robust evidence to guide decision-making in this population is lacking. This multicentre observational cohort study used data from the COREPEX registry including women who underwent anterior or total pelvic exenteration between 2005 and 2023 across 20 European tertiary referral centres. The primary outcome was overall survival (OS); secondary outcomes were progression-free survival (PFS) and major postoperative complications. Associations were assessed using multivariable Cox and binomial regression models adjusted for relevant covariates. Among 861 women, 79 (9.2%) had vulvar cancer. Median follow-up was 49 months for OS and 40 months for PFS. Women with vulvar cancer were older and more often overweight. Five-year OS was 32% (95% CI, 19-46) in vulvar cancer versus 29% (95% CI, 25-34) in other cancers, adjusted HR 1.05 (95% CI, 0.75-1.46). Five-year PFS was 34% versus 29%, adjusted HR 0.96 (95% CI, 0.69-1.34). Major complications occurred in 33% vs 29%, adjusted RR 1.12 (95% CI, 0.77-1.58). Lymph node metastases, positive margins, and recurrent or persistent disease independently predicted poorer survival. Despite their older age, women with vulvar cancer had survival and morbidity comparable to those with other gynaecological malignancies. These findings support pelvic exenteration as a curative option for selected women with vulvar cancer when complete resection is feasible.

Levonorgestrel-releasing intra-uterine device alone for managing early-stage endometrial cancer and endometrial hyperplasia with atypia in patients unfit for surgery: the ENDOIUD study

This study aimed to clarify the role of levonorgestrel-releasing intra-uterine device as a stand-alone therapy in managing patients with endometrial atypical hyperplasia/endometrial cancer who are not suitable for surgery, through the evaluation of cause-specific survival and the control of vaginal bleeding. This is a retrospective, multi-center study conducted in 9 referral gynecologic centers in Italy. Data regarding the clinical and oncological outcomes of patients with endometrial atypical hyperplasia/endometrial cancer (International Federation of Gynecology and Obstetrics Stage I) were analyzed. Patients were judged unsuitable for surgery due to an American Society of Anesthesiologists score ≥3 and the presence of multiple severe co-morbidities and, therefore, triaged to receive levonorgestrel-releasing intra-uterine device alone. A total of 78 women were enrolled. Fifteen patients (19.2%) had a diagnosis of endometrial atypical hyperplasia, whereas the other 63 (80.8%) had endometrial cancer. The baseline hemoglobin levels averaged 11.6 (range; 6-16), increasing to 12.1 (range; 7.8-14.9) during follow-up after levonorgestrel-releasing intra-uterine device insertion (p = .003). No patient experienced any side effects, and bleeding control was rated as excellent in most patients. Median disease-free survival was 43 months (range; 5-120) and median overall survival was 45 months (range; 5-120). Levonorgestrel-releasing intra-uterine device alone is a safe and effective approach, showing no side effects, and a promising oncological outcome in women with early-stage endometrial atypical hyperplasia/endometrial cancer unfit for surgery. Future prospective studies are required to clarify how to select patient candidates for this therapy and how to predict response to levonorgestrel-releasing intra-uterine device.

Neoadjuvant chemotherapy followed by interval surgery versus primary debulking surgery in FIGO stage III-IV epithelial ovarian cancer: A systematic review and meta-analysis.

To compare survival and perioperative outcomes of Primary debulking surgery (PDS) versus neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) in newly diagnosed FIGO stage III-IV ovarian cancer. Primary outcomes were overall survival (OS) and progression-free survival (PFS). MEDLINE, Embase, CENTRAL, Web of Science, Scopus, Cochrane Library, major conference proceedings (inception to July 13, 2025) STUDY SELECTION: Phase-III randomized trials comparing survival outcomes between PDS and NACT-IDS, enrolling adults with newly diagnosed stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. Following PRISMA, two reviewers independently screened, extracted and assessed risk-of-bias (RoB 1). Random-effects meta-analysis estimated pooled hazard ratios (HRs) for OS/PFS and risk ratios (RRs) for binary endpoints. Heterogeneity was quantified with the I² statistic. PROSPERO (CRD420251056445). Five RCTs (n = 2380 women), including one conference-only report, met criteria. NACT-IDS yielded no difference in OS (HR 1.00; 95 % CI 0.90-1.12; I² = 16 %) and PFS (HR 1.03; 95 % CI 0.92-1.16; I² = 39 %) versus PDS. Grade ≥ 3 perioperative complications were significantly less frequent with NACT-IDS (RR 0.43; 95 % CI 0.25-0.74; I² = 75 %) while CC-0 rates were higher (RR 2.02; 95 % CI 1.26-3.24; I² = 94 %). In FIGO stage III-IV, NACT-IDS achieves survival endpoints similar to PDS, while increasing the likelihood of complete macroscopic resection and reducing severe perioperative morbidity. Upfront surgery in advanced ovarian cancer management should likely be reserved for patients with feasible complete resection and presumed low morbidity.

Exploring the cost-effectiveness of the OSNA method for patients facing endometrial cancer: Insights from a single-institution experience

The one-step nucleic acid amplification (OSNA) method has emerged as a potential alternative to ultrastaging for diagnosing lymph node metastasis. This study aims to assess the cost-effectiveness of the OSNA technique compared to ultrastaging for detecting SLN metastasis in patients with early-stage endometrial cancer (EC). This retrospective, observational, single-center study included 30 patients with EC who underwent surgical treatment. SLN mapping was performed using an intracervical injection of indocyanine green. SLNs were analyzed and classified as negative, as having isolated tumor cells, micrometastases, or macrometastases. The study evaluated and quantified the costs of the OSNA and ultrastaging procedures in euros. A total of 54 lymph nodes were analyzed using both the OSNA and ultrastaging methods. Concordant negativity was identified in 48 cases (89 %), while micrometastases were detected concordantly in 1 case (1.8 %). The cost for a single ultrastaging lymph node analysis, including immunohistochemistry, is approximately € 250, with a total processing time of 2 days. The cost for a single OSNA analysis is approximately € 236, boasting a significantly shorter processing time of 30-40 min. While materials and staff costs are comparable between both techniques, considering time-related expenses, the OSNA method proves to be more cost-effective than ultrastaging (p < 0.001). The OSNA method demonstrates diagnostic accuracy comparable to histopathological examination in detecting lymph node metastases, reinforcing its reliability for lymph node assessment in patients with EC. Our cost analysis reveals that the OSNA method is more cost-effective than ultrastaging when time-related expenses are considered.

Outcomes of low-risk endometrial cancer with isolated tumor cells in the sentinel lymph nodes: a prospective, multi-center, single-arm, observational study (ENDO-ITC study)

It is unclear whether isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) adversely affect prognosis, especially in low-risk endometrial cancer. In a retrospective study, we showed a worse recurrence-free survival for low-risk endometrial cancer with ITCs than the node-negative group. Our aim is to evaluate whether the likelihood of disease recurrence differs between a prospective cohort of patients with low-risk endometrial cancer with ITCs and an historical cohort with negative SLNs. We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. This is a prospective, multi-center, single-arm observational study. Consecutive patients with low-risk endometrial cancer with ITCs in the SLNs will be accrued. Observation only will be suggested after surgery. We will include patients with endometrial cancer undergoing pelvic SLN biopsy and ultra-staging with the following characteristics: endometrioid histology, grades 1 to 2, <50% myometrial invasion, without substantial/extensive lympho-vascular space invasion. ITCs in SLNs are defined as tumor cell aggregates ≤0.2 mm or <200 cells. The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. With a sample size of 132 women with low-risk endometrial cancer and ITCs, a 1-sided log-rank test achieves 85% power at a 0.05 significance level to detect an HR of 2.1. The expected number of events during the study is 17.3. The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. ClinicalTrials.gov: NCT06689956.

The impact of Substantial LYMphovascular space invasion on sentinel lymph nodes status and recurrence in Endometrial Cancer patients: SLYM-EC a multicenter retrospective study

To evaluate the prognostic impact of substantial lymph vascular space invasion (LVSI) on the sentinel lymph node involvement and recurrence rate of patients with apparent uterine-confined endometrial cancer. We enrolled consecutive patients with apparent confined endometrial cancer who underwent surgical staging with sentinel node mapping from 14 European reference centers. LVSI was analyzed semi-quantitatively, according to a 3-tiered scoring system classified as absent, focal, and substantial. Among 2352 eligible patients, 1980 were included in the analysis. Upon final pathology 226 patients (11.4 %) had SLNs involvement. LVSI was diagnosed focal in 152 patients (7.7 %), whereas 357 patients (18.0 %) showed substantial LVSI. Focal or substantial LVSI rate were significantly higher in patients with positive SLNs when compared to patients without SLNs involvement (p < 0.0001). On overall patient-based analysis, the sensitivity, specificity, positive predictive value, and negative predictive value of LVSI for sentinel lymph node metastases were 73 %, 80 %, 32 %, and 96 %, respectively. The 3-year multivariate analysis of recurrence-free survival showed that only the presence of substantial LVSI, and grade 3 disease were associated with relapse. Neither positive sentinel lymph node, deep myometrial infiltration, nor age at surgery were statistically significant. In patients having undergone sentinel node biopsy, positive LVSI demonstrated moderate sensitivity and reasonable specificity in detecting SLN involvement. LVSI positivity does not correlate with nodal involvement. The presence of substantial LVSI remains a strong independent risk factor for recurrence, indicating a role for potential hematogenous dissemination in patients with early-stage disease.

Application of novel algorithm on a retrospective series to implement the molecular classification for endometrial cancer

The study aimed to validate the Betella algorithm, focusing on molecular analyses exclusively for endometrial cancer patients, where molecular classification alters risk assessment based on ESGO/ESTRO/ESP 2020 guidelines. Conducted between March 2021 and March 2023, the retrospective research involved endometrial cancer patients undergoing surgery and comprehensive molecular analyses. These included p53 and mismatch repair proteins immunohistochemistry, as well as DNA sequencing for POLE exonuclease domain. We applied the Betella algorithm to our population and evaluated the proportion of patients in which the molecular analysis changed the risk class attribution. Out of 102 patients, 97 % obtained complete molecular analyses. The cohort exhibited varying molecular classifications: 10.1 % as POLE ultra-mutated, 30.3 % as mismatch repair deficient, 11.1 % as p53 abnormal, and 48.5 % as non-specified molecular classification. Multiple classifiers were present in 3 % of cases. Integrating molecular classification into risk group calculation led to risk group migration in 11.1 % of patients: 7 moved to lower risk classes due to POLE mutations, while 4 shifted to higher risk due to p53 alterations. Applying the Betella algorithm, we can spare the POLE sequencing in 65 cases (65.7 %) and p53 immunochemistry in 17 cases (17.2 %). In conclusion, we externally validated the Betella algorithm in our population. The application of this new proposed algorithm enables assignment of the proper risk class and, consequently, the appropriate indication for adjuvant treatment, allowing for the rationalization of the resources that can be allocated otherwise, not only for the benefit of settings with low resources, but of all settings in general.

Fertility-sparing vs hysterectomy for uterine STUMP: A pragmatic clinical study.

Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy. This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS). Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal. Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.

Patent Blue SLN in Early Ovarian Cancer Prospective Study (FIGO I-II) Evaluating Patent Blue SLN Mapping. Injection Into IP/UO Ligaments in Situ. Goals: Assess Feasibility and Accuracy vs Standard Lymphadenectomy to Minimize Surgical Morbidity

the standard of care in case of early ovarian cancer (stage I or II) is a complete surgery. This surgery includes : hysterectomy (remove of the uterus), bilateral salpingo-oophorectomy (remove of the adnexa), omentectomy (remove of the epiploon), bilateral pelvic lymphadenectomy (remove of pelvic lymph nodes) and para-aortic lymphadenectomy (remove of para-aortic lymph nodes). This procedure is diagnostic, curative and prognostic surgery. In fact, it allows us provider care giver to stratify the stage of the cancer, hence we give the appropriate adjuvant therapy. However, this surgery, especially the extended lymphadenectomy, is associated with some risks: lymphocele, vessel injury, blood loss, morbidity, long recovery period ... In order to reduce these risks, we propose a sentinel lymph node biopsy. This intervention allows us to detect first lymph node relay whether pelvic or para-aortic. In our study, we chose the patent blue dye as a tracer. This tracer is widely used in oncologic surgery (for example in breast cancer) and approved but not in ovarian cancer yet. During surgery for early stage ovarian cancer, we will inject the patent blue dye on both side of the ovarian tumor. Then, we will check for first colorful lymph node, in both pelvic and para-aortic regions. We will send these dissected lymph node to pathology for analysis. Finally, we will continue the procedure as the standard of care. Our objective is to compare the results between the sentinel lymph node and the complete lymphadenectomy and to study the technique of sentinel lymph node biopsy using the blue patent dye as tracer.

Tumor Microenvironment in Ovarian Cancer

A detailed understanding of molecular mechanism of cancer genesis is fundamental to develop innovative and personalized therapies. The new frontier in biomedical research is represented by organoids, a three-dimensional cell culture system obtained from a tissue fragment that accurately reproduces the essential properties of the original tissue in vitro, which could provide a valuable model for explanation of ovarian cancers pathogenesis and will allow to predict the response to a specific therapy. With this research project, we expect to generate ovarian cancer organoids to characterize in vitro interactions and molecular pathway among tumor cells, immune cells, and resident microbiota (intratumoral bacteria and/or microbial-derived molecules).