Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

Spotlight on Compounded Bioidentical Hormones.

BACKGROUND: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. OBJECTIVES: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. METHODS: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, PubMed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. OUTCOMES: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. CONCLUSION AND OUTLOOK: These formulations might provide effective options to best tailor therapies to each patient.

Vulvodynia: A practical guide in treatment strategies.

Vulvodynia is a debilitating condition characterized by chronic vulvar pain, with a detrimental impact on the patient's overall quality of life. Its etiology is multifactorial, but still in the process of being clearly outlined. Vulvodynia is not a single entity. It is a heterogeneous condition characterized by multiple triggers, making it challenging to define a reference standard for its treatment. In this manuscript we selected all articles including the following key criteria: "vulvodynia". The primary outcomes observed included the resolution of chronic pelvic pain, dyspareunia and sexual satisfaction, psychological well-being, and overall quality of life. Most pharmacologic treatments require further evidence to be recommended. On the other hand, non-pharmacologic approaches such as psychotherapy, physical therapy, and surgery have received stronger support. This review summarizes pros and cons of adopting available treatments. Multimodal approaches should be introduced to improve patient outcomes. Further investigations are warranted to improve patients' quality of life.

Advances in small molecule maintenance therapies for high-grade serous ovarian cancer.

INTRODUCTION: Ovarian cancer is one of the most lethal gynecological tumors with a lack of effective treatment modalities especially in advanced/recurrent disease. Nevertheless, recently, new small molecules have emerged as an effective approach for the management of ovarian cancer patients, especially in the maintenance setting. AREAS COVERED: This review summarizes the role of small molecules used in the management of high-grade serous ovarian cancer. The authors performed a critical review of current evidence and ongoing studies. Of note, tyrosine kinase inhibitors (TKIs) and poly(ADP-ribose) polymerase (PARP) inhibitors are the most intriguing medications in this setting. EXPERT OPINION: Protein-targeted therapies against tumor tissues have progressed significantly in the last years due to an enhanced knowledge of the biological and molecular processes of carcinogenesis. Treatment with small molecules allows the targeting of specific proteins involved in cancer biology. TKIs seem promising but further data are necessary to assess the pros and cons of adopting this treatment modality. PARP inhibitors represent the new standard of care for ovarian cancer patients harboring either a BRCA mutation or with homologous recombination deficiency (HRD). Interestingly, the accumulation of data has highlighted that PARP inhibitors provide benefits even in patients with HR proficient tumors.

Age-Adjusted Charlson Comorbidity Index Predicts Survival in Endometrial Cancer Patients.

OBJECTIVE: Comorbidity scores are increasingly used to reduce potential confounding in oncologic research. This is of paramount importance in endometrial cancer (EC) since it is characterized by quite indolent behavior. Here, we aim to evaluate the impact of various comorbidities and concurrent medications used on survival outcomes, adopting the age-adjusted Charlson comorbidity index (A-CCI). DESIGN: This is an observational study. Charts of 257 EC patients were retrieved. METHODS: We retrospectively evaluated data of patients who underwent surgical treatment for EC. A-CCI was calculated by summing the weighted comorbidities and age of each patient. A binomial value was assigned to different comorbidities and different drugs. Oncologic outcomes were evaluated using Cox proportional hazard models adjusted for age. RESULTS: A-CCI ≥3 correlated with more aggressive tumor features (47.6% vs. 26.8%, p = 0.001), higher risk of recurrence (29.7% vs. 11.6%, p = 0.001), death (20.7% vs. 7.1%, p = 0.002), and death due to disease (16.6% vs. 6.3%, p = 0.012). Considering comorbidities and drugs at parsimonious multivariable analysis model: cardiac disease, liver disease, and proton pump inhibitors (PPIs) use were independent predictors of disease-free survival. Cardiac disease, autoimmune disease, and PPIs use were independent predictors of overall survival. Diabetes was the only independent predictor for cause-specific survival. LIMITATIONS: The major limitation of the present study is its retrospective nature and the relatively small sample size that limit the possibility to have firm conclusions. CONCLUSION: Patients with EC are characterized by a high burden of comorbidities. Comorbidities are associated directly with survival outcomes. Further attention is needed to improve the active management of comorbidities soon after EC treatments. Interventional studies are needed to improve patients' outcomes.

Assessing the role of minimally invasive radical hysterectomy for early-stage cervical cancer.

Surgery is the mainstay of treatment in the management of early-stage cervical cancer. Until the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, minimally invasive radical hysterectomy was the recommended approach to treat patients with early-stage disease. The results of the LACC trial questioned the adoption of minimally invasive surgery in cervical cancer. In comparison with the open approach, minimally invasive surgery correlated with worse disease-free and cancer-specific survival. Similarly, other retrospective studies highlighted this correlation, thus corroborating the results of the LACC trials. In the present review, we evaluated current evidence and further prospective of the adoption of minimally invasive radical hysterectomy in cervical cancer. Moreover, we sought to assess some unsolved issues regarding the role of minimally invasive surgery in early-stage cervical cancer patients.

Assessing the role of low volume disease in endometrial cancer.

The role of retroperitoneal staging in endometrial cancer is still unclear. Although the prognostic value of lymphadenectomy has been demonstrated no data support the therapeutic value of nodal dissection. Sentinel node mapping represents an evolution of lymphadenectomy. Sentinel node mapping allows a more accurate identification of low-volume diseases (i.e., micrometastasis and isolated tumor cells) that are not always detectable via conventional histopathological evaluation. Adjuvant therapy might play a role in patients with low-volume disease. However, the presence of isolated tumor cells alone seems to not impact outcomes of endometrioid endometrial cancer patients. Hence, the choice to deliver adjuvant therapies has to be tailored based on uterine factors only. The introduction of molecular and genomic profiling would be useful in selecting appropriate surgical and adjuvant treatments. The molecular-integrated risk profile should be integrated in clinical practice to overcome the need of retroperitoneal staging (in case of non-bulky nodes) in patients at low risk.

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

The puzzle of gynecologic neuroendocrine carcinomas: State of the art and future directions.

Primary gynecologic neuroendocrine carcinomas (gNECs) are a heterogeneous spectrum of rare and highly aggressive neoplasms, accounting for about 2% of all gynecologic malignancies, which mostly resemble the small cell lung carcinoma (SCLC). Due to the lack of standardized treatment guidelines, their management poses a noteworthy clinical challenge. Currently, cumulative data retrieved from the management of SCLC and from retrospective studies supports a multimodality strategy, based on surgery, chemotherapy, and radiotherapy. Nevertheless, the prognosis remains poor and recurrences are extremely frequent. Hence, there is an urgent need for novel treatment options and promising molecular targets. Recently, there has been an increasing interest on the potential role of immune checkpoint inhibitors, especially in the recurrent setting. However, only scant evidence exists and there is still a long road ahead. A solid collaboration between gynecologists and oncologists worldwide is required to improve the treatment of these puzzling tumors.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Hepatobiliary Disease Resection in Patients with Advanced Epithelial Ovarian Cancer: Prognostic Role and Optimal Cytoreduction.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety in terms of prognostic significance and perioperative morbidity and mortality of cytoreduction in patients affected by advance ovarian cancer and hepato-biliary metastasis. METHODS: Patients with a least one hepatobiliary metastasis who have undergone surgical treatment with curative intent of were considered for the study. Perioperative complications were evaluated and graded with Accordion severity Classification. Five-year PFS and OS were estimated using the Kaplan-Meier curve. RESULTS: Sixty-seven (20.9%) patients had at least one metastasis to the liver, biliary tract, or porta hepatis. Forty-four (65.7%) and 23 (34.3%) patients underwent respectively high and intermediate complexity surgery according. Complete cytoreduction was achieved in 48 (71.6%) patients with hepato-biliary disease. In two patients (2.9%) severe complications related to hepatobiliary surgery were reported. The median PFS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) was 19 months [95% confidence interval (CI) 16.2-21.8] and 8 months (95% CI 6.1-9.9). The median OS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) 45 months (95% CI 21.2-68.8 months) and 23 months (95% CI 13.9-32.03). CONCLUSIONS: Hepatobiliary involvement is often associated with high tumor load and could require high complex multivisceral surgery. In selected patients complete cytoreduction could offer survival benefits. Morbidity related to hepatobiliary procedures is acceptable. Careful evaluation of patients and multidisciplinary approach in referral centers is mandatory.

Modified fragility index and surgical complexity score are able to predict postoperative morbidity and mortality after cytoreductive surgery for advanced ovarian cancer.

OBJECTIVE: The aim of this study was to assess the impact of surgical complexity on postoperative complications and mortality, according to patient's frailty (mFI) following surgery for ovarian cancer. METHODS: Patients undergoing cytoreductive surgery for ovarian cancer from 2008 to 2018 were identified from our database. A surgical complexity score from 1 to 3 was used to assess the extent of surgery (simple to complex, respectively). mFI with 11 variables, based on mapping the Canadian Study of Health and Aging Frailty Index to the NSQIP comorbidities was evaluated. Data were analyzed using Fisher exact test, independent sample t-test, and logistic regression. RESULTS: Of 263 patients identified, 33% reported at least one postoperative complication and 6% had severe complications. BMI ≥ 30 (p = 0.04) increased mFI (p = 0.04) and high-complexity surgery (p < 0.001) were independent predictors of severe complications (G3-G5). Patients with high frailty index score (mFI ≥ 3) who underwent intermediate or high-complexity surgery were at higher risk of severe complications ranging from 29.4% to 50. CONCLUSIONS: The combined evaluation of mFI and surgical complexity expected may identify patients at higher risk for severe morbidity allowing to stratify patients who are less likely to tolerate a surgical extensive treatment.

Update on surgical treatment of female stress urinary incontinence.

INTRODUCTION: Urinary incontinence is a common condition that negatively impacts quality of life of millions of women. It is a result of a synergy between the structures of pelvic floor in particular levator ani muscle and pelvic connective tissues. Urinary incontinence, increasing with age, is associated with considerable personal and societal expenditure. EVIDENCE ACQUISITION: Systematic data search performed using PubMed/Medline database up to August 20, 2020. Focus was only for English language publications of original studies on urinary incontinence and in particular stress urinary incontinence. EVIDENCE SYNTHESIS: Given the basis of published evidence and the consensus of European experts, this study provides an updated overview on clinical applications and surgical procedures of urinary incontinence. CONCLUSIONS: Urinary incontinence is an underestimated health problem. Many surgical options exist for women with stress urinary incontinence. Nevertheless, new strategies need to be evaluated in order to improve quality of life of patients.

Urinary incontinence in women: state of the art and medical treatment.

INTRODUCTION: Urinary incontinence, the involuntary loss of urine, is a common condition that affects approximately 50% of adult women. This condition increases with age, affecting 10% to 20% of all women and up to 77% of elderly women residing in nursing homes. EVIDENCE ACQUISITION: Systematic data search performed using PubMed/MEDLINE database up to July 20, 2020. Focus was only for English language publications of original studies on urinary incontinence. EVIDENCE SYNTHESIS: Given the basis of published evidence and the consensus of European experts, this study provides an updated overview on clinical applications and surgical procedures of urinary incontinence. CONCLUSIONS: Urinary incontinence is an underestimated health problem. Patients need an overview of their health condition through a detailed anamnestic collection and physical examination to identify the type of incontinence and offer the best treatment.

Recurrent mantle cell lymphoma in the uterine cervix: a case report.

BACKGROUND: Mantle cell lymphoma is one of several subtypes of non-Hodgkin lymphoma. Cervical relapse of non-Hodgkin lymphoma is a very rare condition that has a variable and nonspecific presentation and may resemble other neoplastic or inflammatory conditions. CASE PRESENTATION: Our patient was a 58-year-old Caucasian woman who experienced relapse of mantle cell lymphoma with cervical localization. She complained of postmenopausal vaginal bleeding, bladder pressure, and rapid growth of a cervical lesion. An irregular tumor mass of the cervix was visualized during gynecological examination, with findings highly suggestive of locally advanced cervical cancer. Surprisingly, the biopsies showed an extra nodal relapse of mantle cell lymphoma in the cervix. The rarity of this presentation and the scarcity of clinical studies make this type of recurrence very aggressive and difficult to treat. CONCLUSIONS: Obtaining a definitive histological diagnosis by biopsy or surgical resection and starting appropriate therapy are essential for recovery and treatment of these patients, even if the prognosis is poor.

The Role of 2D/3D Ultrasound to Assess the Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer.

INTRODUCTION: Different imaging techniques were introduced to improve preoperative clinical staging of locally advanced cervical cancer (LACC) with transvaginal ultrasound (TV-US) or transrectal ultrasound (TR-US) representing a promising staging technique in the evaluation of the local extension of the disease for invasive tumors. The aim of this study was to evaluate the response to neoadjuvant chemotherapy (NACT) in LACC by 2D/3D ultrasound examination. MATERIALS AND METHODS: We prospectively enrolled patients affected by histologically and clinically confirmed LACC. All patients were scheduled for 3 cycles of platinum-based NACT followed by radical surgery. The ultrasound examination was performed at every cycle and within 10 days before surgery. The parameters evaluated were: the volume (automatically computed by the VOCAL software) and the mass vascularization. RESULTS: From March 2010 to March 2019, 157 women were recruited. Among these patients, 12 of them were excluded: 6 for the presence of distant metastases, 4 for rare histology, and 2 for severe comorbidities not allowing the protocol treatment. Seventeen patients after NACT were excluded because they were not amenable to radical surgery. Thus, 128 were considered for the final analysis of whom 106 (83%) were considered responders to NACT by histology. The sensibility and specificity of ultrasound with regard to the response to chemotherapy compared to histological specimen were 94 and 82%, respectively, with an accuracy of 92%. The positive predictive value and negative predictive value were 96 and 75%, respectively. Finally, we found that nonetheless there was a trend towards a continuous response to chemotherapy among patients who were considered responders to NACT at pathological examination; the major volume and vascularization index (VI) reduction were observed during the first 2 cycles (74, 71% and 47, 63%, respectively). On the contrary, non-responders showed an initial reduction of the VI (4.86 consisting of 33%, 95% CI 0.79-8.92, p = 0.013), but no significant modification in tumour volume along NACT. CONCLUSION: 2D/3D ultrasound is useful in assessing early response to NACT in patients with LACC.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Evaluation of Parametrial Status in Locally Advanced Cervical Cancer Patients after Neoadjuvant Chemotherapy: A Prospective Study on Diagnostic Accuracy of Three-Dimensional Transvaginal Ultrasound.

OBJECTIVES: To analyze the diagnostic accuracy of two-dimensional (2D) and three-dimensional transvaginal ultrasound (3D TV-US) for evaluation of parametrial status in locally advanced cervical cancer patients after neoadjuvant chemotherapy (NACT), using histology as the gold standard. METHODS: Consecutive patients with histologically confirmed cervical cancer were staged according to FIGO (International Federation of Gynaecology and Obstetrics) criteria. All IB2-IIIB FIGO stage patients were examined by 2D and 3D TV-US and magnetic resonance imaging (MRI) at the diagnosis time (T0) and after NACT. At T0, the US evaluation of parametrial involvement was compared to MRI before treatment. The results of US and MRI examinations of parametrial status after NACT were compared with the histological specimen. RESULTS: We enroled 51 consecutive patients in the study. Before chemotherapy, clinical examination under anaesthesia identified parametrial involvement in 48 patients, ultrasonography in 46 patients, and MRI in 49 patients. The agreement between US and MRI was 94%. The sensitivity of US for parametrial status was 93.8%, with a positive predictive value of 97.8%, using MRI as the standard. The correlation between US and MRI was statistically significant (p = 0). After chemotherapy, histological examination of surgical specimens identified parametrial involvement in 3 patients. Ultrasonography correctly identified those cases with parametrial infiltration, recording a sensitivity of 100%, specificity of 90.9%, positive predictive value of 50%, and negative predictive value of 100%. The MRI had a sensitivity of 100%, specificity of 45.5%, positive predictive value of 14.3%, and negative predictive value of 100%, respectively. The concordance in the identification of the presence/absence of infiltration between US and MRI with histology was 90% (p = 0.001) and 61%, respectively, after chemotherapy treatment. Particularly, in defining the degree of infiltration, the agreement between US and MRI with histology was 90 and 58%, respectively. CONCLUSION: In locally advanced cervical cancer patients, 2D/3D TV-US can be considered accurate in the evaluation of parametrial infiltration to assess the response to NACT. It could be included as a diagnostic method in the preoperative work-up of cervical cancer.

Immune Checkpoint Inhibitors: A Promising Choice for Endometrial Cancer Patients?

Although around 80% of endometrial cancers are diagnosed at early stages and present with a 5-year survival rate exceeding 95%, patients with advanced and recurrent disease show a poor prognosis and low response rates to standard chemotherapy. In the era of targeted therapy, the great advances in the understanding of programmed death-ligand 1 (PD-L1) upregulation in cancer cells, which is responsible for tumor immune escape, have contributed to the increasing interest in immune checkpoint inhibitors as a promising strategy for the treatment of several refractory solid malignancies, including endometrial cancer. Several clinical trials have investigated the efficacy and safety of immune checkpoint inhibitors in endometrial cancer, which already led to the approval of the anti-programmed cell death protein 1 (anti-PD-1) antibody pembrolizumab as a satisfactory alternative for selected patients with unresectable or metastatic disease. As the future of cancer treatment will probably rely on combination therapy strategies, currently, innovative ongoing trials are exploring the potential role of immune checkpoint inhibitors associated with chemotherapy, radiotherapy, and other targeted therapies. Moreover, further research is warranted to discover new specific biomarkers that can accurately predict the response to immunotherapy.