Locally advanced and metastatic endometrial cancer: Current and emerging therapies.

Until recently, patients diagnosed with locally advanced and metastatic endometrial cancer faced significant challenges in their treatment due to limited options and poor prognostic outcomes. The sequencing of tumors has been a major advancement in its management. It has led to The Cancer Genome Atlas classification currently used in clinical practice and the initiation of several clinical trials for innovative treatments targeting principally signaling pathways, immune checkpoints, DNA integrity, growth factors, hormonal signaling, and metabolism. Numerous clinical trials are investigating a combinatorial approach of these targeted therapies to counter tumoral resistance, cellular compensatory mechanisms, and tumor polyclonality. This review provides a comprehensive overview of historical, current, and promising therapies in advanced and metastatic endometrial cancer. It particularly highlights clinical research on targeted and hormonal therapies, but also immunotherapy, reflecting the evolving landscape of treatment modalities for this disease.

Diagnostic Performance of Immunohistochemistry Compared to Molecular Techniques for Microsatellite Instability and p53 Mutation Detection in Endometrial Cancer.

Molecular algorithms may estimate the risk of recurrence and death for patients with endometrial cancer (EC) and may impact treatment decisions. To detect microsatellite instabilities (MSI) and p53 mutations, immunohistochemistry (IHC) and molecular techniques are used. To select the most appropriate method, and to have an accurate interpretation of their results, knowledge of the performance characteristics of these respective methods is essential. The objective of this study was to assess the diagnostic performance of IHC versus molecular techniques (gold standard). One hundred and thirty-two unselected EC patients were enrolled in this study. Agreement between the two diagnostic methods was assessed using Cohen's kappa coefficient. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the IHC were calculated. For MSI status, the sensitivity, specificity, PPV and NPV were 89.3%, 87.3%, 78.1% and 94.1%, respectively. Cohen's kappa coefficient was 0.74. For p53 status, the sensitivity, specificity, PPV, and NPV were 92.3%, 77.1%, 60.0% and 96.4%, respectively. Cohen's kappa coefficient was 0.59. For MSI status, IHC presented a substantial agreement with the polymerase chain reaction (PCR) approach. For the p53 status, the moderate agreement observed between IHC and next generation sequencing (NGS) methods implies that they cannot be used interchangeably.

Concordance between preoperative ESMO-ESGO-ESTRO risk classification and final histology in early-stage endometrial cancer.

OBJECTIVE: To evaluate the concordance between preoperative European Society for Medical Oncology (ESMO)-European Society of Gynaecological Oncology (ESGO)-European SocieTy for Radiotherapy and Oncology (ESTRO) risk classification in early-stage endometrial cancer (EC) assessed by biopsy and magnetic resonance imaging (MRI) with this classification based on histology of surgical specimen. METHODS: This bicentric retrospective study included women diagnosed with early-stage EC (≤stage II) who had a complete preoperative assessment and underwent a surgical management from January 2011 to December 2018. Patients were preoperatively classified into 3 degrees of risk of lymph node (LN) involvement based on biopsy and MRI. Based on final histological report, patients were re-classified using the preoperative classification. Concordance between the preoperative assessment and definitive histology was calculated with weighted Cohen's kappa coefficient. RESULTS: A total of 333 women were included and kappa coefficient of preoperative risk classification was 0.49. The risk was underestimated and overestimated in 37% and 10% of cases, respectively. Twenty-nine percent of patients had an incomplete LN staging according to the degree of risk of re-classification. The observed discordance in the risk classification was attributed to MRI in 75% of cases, to biopsy in 18% and in 7% to both (p<0.001). Kappa coefficient for concordance was 0.25 for MRI and 0.73 for biopsy. CONCLUSION: Concordance between preoperative ESMO-ESGO-ESTRO risk classification and final histology is weak. Given that the risk was underestimated in the majority of patients wrongly classified, sentinel LN procedure instead of no LN dissection could be an option offered to preoperative low-risk patients to decrease the indication of second surgery for re-staging and/or to avoid toxicity of adjuvant radiotherapy.

Outcomes after open and laparoscopic appendectomy during pregnancy: A meta-analysis.

OBJECTIVES: Acute appendicitis is the most prevalent cause of non-obstetrical surgical disease during pregnancy. There is no consensus on the optimal surgical management of acute appendicitis in pregnancy. Our aim is to identify surgical and obstetrical outcomes of laparoscopic (LA) and open approach (OA) in pregnant patients with acute appendicitis. STUDY DESIGN: Medline, Scopus, Google Scholar, Cochrane CENTRAL Register of Controlled Trials and Clinicaltrials.gov databases were searched for articles published up to May 2017, along with the references of all articles. Prospective and retrospective trials reporting outcomes among pregnant women undergoing laparoscopic and open appendectomy were included. Of the 493 records screened, 20 were eligible for meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Statistical meta-analysis was performed using the RevMan 5.3 software. RESULTS: A total of 6210 pregnant women from twenty studies were included in meta-analysis. Laparoscopic appendectomy was associated with significantly lower overall complication rates and shorter hospital stays (1835 patients OR 0.48 95% CI 0.29, 0.80 p = 0.005). While the open appendectomy group showed prolongation of gestational age for term deliveries, laparoscopic appendectomy patients had higher rates of fetal loss (543 patients MD -0.46 weeks 95% CI-0.87 to -0.04, p = 0.03 and 4867 patients OR 1.82 95% CI 1.30 to 2.57, p = 0.0006, respectively). CONCLUSIONS: Current literature remains inconclusive on the optimal approach of appendectomy in pregnant women. Further larger-volume studies are needed in order to elucidate the critical effect of laparoscopic appendectomy on fetal loss rates.