Irina Tripac

Neuroendocrine tumors of the gynecological tract: A narrative literature review

Neuroendocrine neoplasms (NENs) of the gynecological tract are a rare, heterogenous and aggressive group of neoplasms, with high recurrence rates and poor prognosis. In this review we focus on NENs of the gynecological system emphasizing the classification, epidemiological and clinical characteristics of NENs across the gynecological tract (cervix, endometrium, ovary, vagina, and vulva), risk/prognostic factors, pathology and molecular biology (including actionable genomic mutations), imaging, staging and the most effective treatment modalities in the "standard of care" approach as well as the pipeline products. We also focused on metastatic spreading patterns of gynecological NENs. We searched for all available literature reviews, interventional studies, short series, case reports and meta-analyses published from 1990 to 2024. Deteriorated survival rate is essentially impacted by early development of lymph node, distant organ metastases and vascular propagation toward rapid extra-pelvic metastasis to the brain, liver, lung, bone marrow, lymph nodes and bones. Management of NENs needs to be customized on a case-based manner and comprises a multidisciplinary approach that involves gynecologists, surgeons, medical oncologists, radiologists, radiation oncologists, nuclear medicine specialists, pathologists, molecular biologists, qualified nurses etc. The treatment of extrapulmonary NENs arising in the female genital tract is basically extrapolated from that for small cell lung cancer. This includes, but is not limited to: surgery, chemotherapy, radiotherapy, peptide receptor radionuclide therapy, somatostatin analogs, and immunotherapy as well as investigational drugs in rare prospective clinical trials. Establishing modern therapeutic thesaurus is conditioned by the existence of well-designed clinical trials targeting a tumor's genomic profile and the incorporation of these data into the actual treatment landscape.

Regression of high-grade squamous intraepithelial cervical lesions and associated risk factors (RECER)

Avoiding conization may reduce the risk of pre-term labor in future pregnancies, making conservative treatment of high-grade cervical dysplasia an increasingly discussed approach, especially for younger patients. However, data on the integration of individual predictive factors into routine clinical practice remain limited. The primary objective of the Regression of High-Grade Squamous Intraepithelial Cervical Lesions and Associated Risk Factors (RECER) study is to assess the rate of spontaneous regression in high-grade cervical squamous dysplasia (cervical intraepithelial neoplasia [CIN] 2 and 3) and identify associated predictive factors within clinical practice, without necessitating conization. We hypothesize that the characterization of cervical lesions, including colposcopic findings and patient-specific factors, along with a sufficient rate of spontaneous regression, will aid in identifying a subgroup of patients who may derive the greatest benefit from conservative management of high-grade cervical lesions. The RECER trial is a multi-center prospective cohort study. Patients with histologically confirmed high-grade squamous intraepithelial lesions (CIN 2 or 3) undergo colposcopic assessments every 4 months. Colposcopic images are compared to evaluate lesion dynamics. In case of progression, conization is indicated, whereas in case of regression, documentation of a biopsy with low-grade dysplasia (CIN 1) or no dysplasia is required. Patients with stable disease are further followed up. Patients aged 18 to 40 years with bioptically confirmed high-grade lesion (CIN 2 or 3), a fully visible squamo-columnar junction, and a willingness to undergo conservative management can be included. Excluded are patients with unsatisfactory colposcopy, pregnancy, glandular lesions, invasive disease, or a history of treatment for severe cervical dysplasia. The primary end point is the regression rate of high-grade cervical dysplasia. 300 patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: As of October 2024, a total of 127 patients have been recruited from 4 participating sites across 3 countries. Estimated date of last patient enrollment: September 2026; estimated date for results presentation: January 2028. Clinicaltrials.gov: NCT06147388.

Access to molecular classification in endometrial cancer recommended by ESGO–ESTRO–ESP guidelines: multi-national survey in Eastern Europe

Advances in tumor biology have transformed endometrial cancer management. Since 2021, ESGO-ESTRO-ESP (European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology-European Society of Pathology) guidelines have incorporated molecular classification, which is essential in the 2025 update. Its implementation in Eastern Europe remains unclear. This study evaluated the availability, reimbursement, and integration of molecular classification at national and institutional levels. A 2-phase cross-sectional online survey was conducted from December 2024 to September 2025. National coordinators from 17 European Society of Gynaecological Oncology-affiliated countries reported on access, reimbursement, and guidelines. A second survey targeted 67 treatment centers to assess institutional practices. Full molecular profiling (p53-abnormal, POLE-ultra-mutated, mismatch repair-deficient) was available in 29.4% of countries, with partial access in 70.6%. Lack of reimbursement and accredited laboratories were the main barriers. At least 1 test was publicly funded in 58.8% of countries: p53 and mismatch repair-deficient immunohistochemistry in 70.0% and POLE-ultra-mutated next-generation sequencing in 29.4%. National guidelines existed in over half of the countries, but few included molecular classification. At the institutional level, testing was routine in 41.0% of centers, selective in 27.9%, and unavailable in 31.1%. Overall, 55.8% reported access via local or external laboratories. Comprehensive classification was significantly more available in settings with national/public reimbursement (79.2% vs 18.9%, p < .0001). POLE-ultra-mutated testing was more accessible in private than public hospitals (42.9% vs 33.3%, p = .006), while p53 immunohistochemistry was more common in high-volume centers (97.5% vs 76.2%, p = .01). Access to molecular classification in Eastern Europe remains limited because of insufficient reimbursement and laboratory resources. Addressing these disparities is essential to support equitable treatment and improve outcomes.

Analysis of the molecular profile of endometrial cancer depending on microsatelite instability

The absence of precise classification and effective predictive biomarkers in endometrial cancer (EC) leads to suboptimal treatment decisions and outcomes, underscoring the urgent need for improved diagnostic and therapeutic approaches. Endometrial cancer represents 4.8 % of the cases of malignant tumors, being in the sixth place worldwide in terms of incidence of malignant tumors in women. The treatment of endometrial cancer, especially stage I, which affects 70-75 % of patients, remains a subject of debate. According to the current European Society of Medical Oncology (ESMO) recommendations, for the management of patients with endometrial cancer, the treatment strategy is influenced by the results of risk stratification. Regarding endometrial cancer, a large number of prognostic factors are described, which create certain difficulties in their application in clinical practice. Most factors are morphological, and information about them is obtained after surgery on the basis of a standard histological examination. Of particular interest is the study of risk factors in the case of individual endometrial cancer variants. The molecular classification of endometrial tumors has the potential to become an indispensable element of histopathological classification, which would contribute to determining the prognosis and treatment strategies of the disease. In addition, it can lead to the development of a new targeted therapy, as well as to the implementation of molecular diagnostic tests for the detection of endometrial cancer in the early stages, when the prognosis is much more favorable. Despite the large amount of research which focuses on the study of the biological and molecular aspects of endometrial cancer, currently none of the tumor markers is recommended for widespread clinical use in endometrial cancer because there is insufficient information concerning their application into clinical practice.