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(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.

(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.

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.

Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies due to the high prevalence of advanced stages of diagnosis and the high rate of recurrence. Furthermore, the heterogeneity of OC tumors contributes to the rapid development of resistance to conventional chemotherapy. In recent years, in order to overcome these problems, targeted therapies have been introduced in various types of tumors, including gynecological cancer. However, the lack of predictive biomarkers showing different clinical benefits limits the effectiveness of these therapies. This requires the development of preclinical models that can replicate the histological and molecular characteristics of OC subtypes. In this scenario, organoids become an important preclinical model for personalized medicine. In fact, patient-derived organoids (PDO) recapture tumor heterogeneity with the possibility of performing drug screening. However, to best reproduce the patient's characteristics, it is necessary to develop a specific extracellular matrix (ECM) and introduce a tumor microenvironment (TME), which both represent an actual object of study to improve drug screening, particularly when used in targeted therapy and immunotherapy to guide therapeutic decisions. In this review, we summarize the current state of the art for the screening of PDOs, ECM, TME, and drugs in the setting of OC, as well as discussing the clinical implications and future perspectives for the research of OC organoids.

Endometrial cancer (EC) is a deleterious condition which strongly affects a woman's quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences.