Background/Objectives: Cancer immunotherapy through the use of PD-1/PD-L1 inhibitors have shown significant promise in endometrial carcinoma (EC), particularly in tumors with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), present in approximately 30% of cases. This review evaluated PD-L1 and PD-1 expression as potential biomarkers for immunotherapy response in EC, focusing on their relationship with MSI status. Methods: A systematic review, adhering to PRISMA guidelines, analyzed studies from MEDLINE and Embase until February 2023 on PD-1/PD-L1 expression in EC stratified by MSI status, including diverse study designs but excluding conference abstracts, with independent screening, data extraction, and additional reference checks to ensure comprehensive coverage. Results: A systematic analysis of 10 studies found that PD-L1 expression was more frequently expressed in MSI tumors (49%) compared to microsatellite-stable tumors (MSS) (33.5%), while PD-1 was expressed in 58% of MSI cases and 48% of MSS cases. Despite these findings, the prognostic value of PD-L1/PD-1 remains uncertain, with conflicting results regarding their association with survival outcomes. PD-L1 expression varied across molecular subtypes, being highest in POLE-mutated tumors (76.56%) and serous carcinomas (73%). Differences in PD-L1 expression between primary and metastatic sites were also noted, complicating its use as a biomarker. Conclusions: The assessment of PD-L1 expression in EC could represent a valuable option for selecting patients who may benefit from immune checkpoint inhibitors (ICI), including those in the MSS cohort, thereby ensuring a more tailored and personalized treatment strategy.

Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies. These studies evaluated stromal (sTILs) and intra-epithelial (ieTILs) TILs before and after NACT. sTIL responses varied, impacting prognostic outcomes, and ieTILs increased in some patients without clear survival associations. PD-L1 expression after NACT correlated with improved overall survival (OS), and increases in granzyme B+ and PD-1 correlated with longer progression-free survival (PFS). Remarkably, reduced FoxP3+ TILs post-NACT correlated with better prognosis. NACT often increases sTIL/ieTIL and CD8+ subpopulations, but their correlation with improved PFS and OS varies. Upregulation of co-inhibitory molecules, notably PD-L1, suggests an immunosuppressive response to chemotherapy. Ongoing trials exploring neoadjuvant ICIs and chemotherapy offer promise for advancing OC treatment. Standardized measurements assessing TIL density, location, and heterogeneity are crucial for addressing genetic complexity and immunological heterogeneity in OC.

Objectives: To analyze the role of PCI variation (Δ-PCI) before and after neoadjuvant chemotherapy (NACT) in an interval cytoreductive surgery (ICS) setting with the aim to propose a scoring model for predicting both complete cytoreduction and histopathologic response. Methods: A total of 50 consecutive patients who underwent ICS at our institution were prospectively collected between January-2020 and December-2023. PCI was assessed at exploratory surgery and at ICS. The clinical and histopathological response to NACT was determined by Δ-PCI and CRS. A cut-off value for Δ-PCI, to predict complete cytoreduction, histopathological response, and both together, was identified using a receiver operating characteristic (ROC) curve. The Kaplan–Meier test was used to define disease-free survival (DFS) based on the Δ-PCI cut-off value. Results: Complete cytoreduction was achieved in 82% of patients, with a median Δ-PCI score at ICS of 12 (range 7–29). The remaining 18% had a median Δ-PCI score at IDS of 8 (range 4–11). The best predictor of complete cytoreduction, histopathologic response CRS 3, and both was the Δ-PCI score, with an area under the curve (AUC) of 0.85 (0.73–0.96), 0.98 (0.94–1.00) and 0.88 (0.75–0.96), respectively; ROC curve analysis determined a Δ-PCI cut-off of 8, 17 and 15, respectively. Δ-PCI ≥ 15 as a predictor for both complete cytoreduction and histopathologic response CRS 3 with a median DFS of 26 months for Δ-PCI ≥ 15 versus 12 months for Δ-PCI < 15 (p = 0.02). Conclusions: Δ-PCI (cut-off ≥ 15) is a predictive model for complete cytoreduction, histological response CRS 3, and improved DFS.

(1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4–5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment.

Background: The Endometriosis Fertility Index (EFI), is a crucial validated surgical tool used for predicting fertility outcomes in women with endometriosis. This study aims to assess the concordance between a preoperative clinical and instrumental EFI evaluation (uEFI) and the EFI score obtained during an exploratory laparoscopy prior to surgery (sEFI). Methods: This study presents preliminary data from a broader observational cohort study. The Least Function score for the uEFI was calculated using a modified version of the original surgical EFI by incorporating a clinical examination, advanced ultrasound, and hysterosalpingo-foam sonography (HyFoSy). Results: The preoperative estimation of the EFI (uEFI) demonstrated a high concordance (k = 0.695, ρs = 0.811) with the sEFI. Remarkably, the surgical interventions led to a significant improvement in the EFI values, with 80% of the intermediate EFI transitioning to a high level, thereby highlighting the positive impact of surgery on fertility outcomes. Conclusion: This study highlights the accuracy of preoperative EFI estimation (uEFI) and its strong agreement with intraoperative assessment. It underscores the potential of a preoperative management tool to guide the allocation of infertile women with endometriosis to operative laparoscopy, direct assisted reproductive technology (ART), or spontaneous attempts at pregnancy.

OBJECTIVE:We aimed to compare the clinical utility and diagnostic accuracy of the ADNEX model, ROMA score, RMI I, and RMI IV, as well as two serum markers (CA125 and HE4) in preoperative discrimination between benign and malignant adnexal masses (AMs). METHODS:We conducted a retrospective study extracting all consecutive patients with AMs seen at our Institution between January 2015 and December 2020. Accuracy metrics included sensitivity (SE), specificity (SP), and area under the receiver operating characteristic curve (AUC), and their 95% confidence intervals (CI) were calculated for basic discrimination between AMs. Model performance was evaluated in terms of discrimination ability and clinical utility (net benefit, NB). RESULTS:A total of 581 women were included; 481 (82.8%) had a benign ovarian tumor and 100 (17.2%) had a malignant tumor. The SE and SP of CA125, HE4, ROMA score, RMI I, RMI IV, and ADNEX model were 0.60 (0.54-0.66) and 0.80 (0.76-0.83); 0.39 (0.30-0.49) and 0.96 (0.94-0.98); 0.59 (0.50-0.68) and 0.92 (0.88-0.95); 0.56 (0.46-0.65) and 0.98 (0.96-0.99); 0.54 (0.44-0.63) and 0.96 (0.94-0.98); 0.82 (0.73-0.88) and 0.91 (0.89-0.94), respectively. The overall AUC was 0.76 (0.74-0.79) for CA125, 0.81 (0.78-0.83) for HE4, 0.82 (0.80-0.85) for ROMA, 0.86 (0.84-0.88) for RMI I, 0.83 (0.81-0.86) for RMI IV, and 0.92 (0.90-0.94) for ADNEX. The NB for ADNEX was higher than other biomarkers and models across all decision thresholds between 5% and 50%. CONCLUSIONS:The ADNEX model showed a better discrimination ability and clinical utility when differentiating malignant from benign Ams, compared to CA125, HE4, ROMA score, RMI I, and RMI IV.

(1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we collected data on 51 patients diagnosed with NSMP EC following the introduction of molecular profiling at our institution. Patients were retrospectively analyzed for estrogen receptor (ER) status, histotype, and grade to identify potential prognostic subgroups. (3) Results: Our analysis identified two distinct subgroups within NSMP EC: low-risk and high-risk, based on ER status, histotype, and grade. The low-risk NSMP group demonstrated significantly better survival outcomes compared to the high-risk group. With a median follow-up time of 16 moths (IQR 13.0-29.7), the disease-free survival (DFS) and overall survival (OS) for the low-risk group were 100%. For the high-risk group, the DFS and OS were 71.4% and 78.6%, respectively, which showed a statistically significantly difference (Log-Rank Mantel-Cox < 0.001). In the high-risk group, four patients experienced recurrence, and three of these patients died. (4) Conclusions: Stratifying NSMP EC into low-risk and high-risk categories based on ER status, histotype, and grade can lead to more accurate prognostic assessments. In time, it may require tailored adjuvant therapies and a personalized treatment.

Introduction/Background The Chemotherapy Response Score (CRS) has been validated to assess the response and prognosis of high-grade ovarian cancer (HGOC) to neoadjuvant chemotherapy (NACT). Similarly, the peritoneal cancer index (PCI) before and after NACT could quantitatively assess the variation of tumor burden in the peritoneal cavity. The aim of the study was to evaluate the ability of PCI to predict histopathologic response to NACT and achieve complete cytoreduction at interval debulking surgery (IDS). Methodology Thirty-two patients with advanced HGOC who underwent IDS at the Padua University Gynecological and Obstetric Clinic between August 2021 and September 2023 were included. Data were prospectively collected. Histopathologic response to NACT was assessed using CRS. The variation of PCI calculated at the exploratory laparoscopy and at IDS was used to assess the clinical response. PCI variation was related to CRS and to complete cytoreduction (R=0). Results The median age was 63,5 years (range 42–81). CRS 1 was found in 13 patients (40,6%), CRS 2 in 14 patients (43,8%), CRS 3 in 5 patients (15,6%). Complete cytoreduction was achieved in 28 patients (87,5%). The median variation of PCI at the exploratory laparoscopy and at IDS in all 32 patients was 9,5 (range 0–34). The median variation of PCI in CRS 1 was 8 (range 0–14), in CRS 2 was 10,5 (range 0–20), in CRS 3 was 18 (range 13–34). The median variation of PCI in patients with R=0 was 10 (range 0–34), in patients with incomplete cytoreduction was 1,5 (range 0–9) (p<0.01). Conclusion The variation of PCI represents a reliable predictor of the histologic response to NACT and complete cytoreduction at IDS. Incorporating PCI evaluation into routine surgical practice before and after NACT could influence the choice of surgical treatment. Disclosures None.

Around 70％of ovarian cancers are diag-nosed at an advanced stage.The Inter-national Federation of Gynecology and Obstetrics(FIGO)classification catego-rises retroperitoneal abdominal lymph node metastases,including pelvic,lumboaortic and hepato-coeliac nodes,as stage ⅢA1,whereas extra-abdominal lymph node involvement,such as cardio-phrenic or inguinal nodes,corresponds to stage IVB.However,within the abdominal cavity,the involvement of different lymph node stations is associated with a markedly different prognosis.

Objective: To describe the surgical technique, assess feasibility, efficacy, and safety of peritonectomy and/or resection of mesentery (P-Rme) during Visceral -Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer (OC). Methods: In April 2009 we registered a protocol study on the safety and feasibility of P-Rme. In the period April 2009-December 2022, 687 patients with FIGO stage IIIC-IV ovarian cancer underwent VPD. One hundred and twenty-nine patients (18.7%) had extensive disease on the mesentery and underwent P-Rme. Feasibility was assessed as the number of procedures completed. Efficacy was measured as the rate of Complete Resection (CR). Safety was defined by the intra- and post -operative morbidity rate specifically associated with these procedures. Results: In all patients P-Rme was successfully completed. P -me was performed in 82 patients and R -me in 47, both procedures in 23 patients. CR was achieved in all 129 patients with an efficacy of 100%. Intra-operatively 5 patients out of 129 experienced small bowel loop surgical devascularization. They required small bowel resection and anastomosis. The procedure specific morbidity was 3.8%. No post -operative complication was related to PRme. At 64 months median follow-up, survival outcomes in the study group were similar to patients in the control group. Conclusion: Overall, almost 20% of the VPD patients needed P-Rme to obtain a CR. P-Rme was a safe and effective step during VPD. The rate of CR in the study group was 100% achieved thanks to the addition of the P-Rme. No procedure specific post -operative complications occurred but 3.8% of the patients had unplanned additional surgery related to these procedures.

Introduction/Background Indication of surgery for ovarian cancer (OC) is often influenced by patients' age, as older individuals are presumed to have lower tolerance for radical surgery. However, limited evidence exists on whether the surgical risks outweigh the benefits of surgery in elderly patients. We aimed to compare perioperative complications between elderly patients (EP) and non-elderly patients (NEP) undergoing surgery for OC. Methodology This retrospective single-center observational study includes consecutive women undergoing surgery for OC between January 2018 and September 2023. Patients were classified as NEP (<75 years) or EP (≥75 years). Chi-square, Fisher's exact, Student-T, or Mann-Whitney tests were used to compare groups. Kaplan-Meier analysis assessed survival. Results 103 patients were included: 28 EP and 75 NEP. No differences were observed in disease characteristics. Staging surgery was performed in 37 patients, primary debulking in 34, and interval debulking in 32, with no differences in type of surgery between EP and NEP (p=0.283). Operative time was shorter in EP (232.3 vs.273.9 minutes; p=0.021). Intra-operative (3.6% vs.13.3%, p=0.281) and post-operative (42.9% vs.33.3%, p=0.489) complication rates were not different between EP and NEP. However, severe complications (Clavien-Dindo III-V) occurred more frequently in EP (35.7% vs.12.0%, p=0.010). EP required reintervention more often than NEP (25% vs.6.7%, p=0.016). The higher rate of severe complications did not delay start of chemotherapy in EP (47.4 days vs.40.7 days in NEP, p=0.060). After a mean follow-up of 26 months, EP presented significantly worse overall survival than NEP (32.7 vs.66.7 months, p<0.001), while no differences were observed in progression-free survival (29.7 vs.33.7 months, p=0.920 ). Conclusion EP undergoing OC surgery do not present a higher rate of perioperative complications compared to NEP. Severe complications are more frequent among EP, who require reintervention more often than NEP. The increased rate of severe complications does not significantly delay adjuvant treatment in EP. Disclosures Authors have no conflict of interest to declare.

Introduction/Background To compare the IOTA Assessment of Different NEoplasias in the adneXa (ADNEX) model, the Ovarian-Adnexal Reporting and Data System (O-RADS) and the combined IOTA Simple Rules (SR) with Simple Rules Risk (SRR) assessment and SR with ADNEX model in the preoperative discrimination of benign and malignant adnexal masses (AM). Methodology We conducted a monocentric retrospective study performed between January-2018 to December-2021 which includes consecutive women with AM. Surgery with histology represented the reference standard. We classified the AM using the ADNEX model, O-RADS and SR in the same cohort of patients. When SR resulted 'inconclusive', we combined SR with SRR assessment and SR with ADNEX model. Sensitivity (SE), specificity (SP) and diagnostic accuracy (DA) were determined for each testing modality to compare the performance of ADNEX model, O-RADS, SR + SRR and SR + ADNEX model. Results Of the 514 women, 400 (77.8%) had a benign ovarian tumor and 114 (22.2%) had a malignant tumor. The malignancy risk threshold was set at >10%. SE, SP and DA of the ADNEX model were 92,1% (95%CI, 85,5%-96,3%), 88,3% (95%CI, 84,6%-91,2%) and 89,1% (86,1%-91,7%), respectively. SE, SP and DA of O-RADS were 93,0% (95%CI, 86,6%-96,9%), 89,3% (95%CI, 85,8%-92,1%) and 90.1% (95%CI, 87,2–92,5%), respectively. When we applied SR, 109 (21.2%) cases resulted inconclusive. SE, SP and DA of the SR + SRR assessment were 87,7% (95%CI, 80,3%-93,1%), 91,8% (95%CI, 88,6%94,3%) and 90,9% (95%CI, 88,0%-93,2%), respectively. SE, SP and DA of the SR + ADNEX model were 90,4% (95%CI, 83,4%-95,1%), 93,3% (95%CI 90,3%-95,5%) and 92,6% (90%-94,7%), respectively. Conclusion The ADNEX model and O-RADS had similar SE and higher SE than SR + SRR assessment and SR + ADNEX model in the preoperative discrimination of malignant and benign AM; SR + ADNEX model had higher DA than ADNEX model, O-RADS and SR + SRR assessment.