Mihai Emil Cãpîlna

Pelvic exenteration for vulvar cancer: contemporary outcomes from a multinational cohort study

Women with vulvar cancer are considerably older than those with other gynaecological malignancies, raising concerns about the tolerability of radical surgery. Yet, for locally advanced or recurrent disease, pelvic exenteration may be the only curative option. Robust evidence to guide decision-making in this population is lacking. This multicentre observational cohort study used data from the COREPEX registry including women who underwent anterior or total pelvic exenteration between 2005 and 2023 across 20 European tertiary referral centres. The primary outcome was overall survival (OS); secondary outcomes were progression-free survival (PFS) and major postoperative complications. Associations were assessed using multivariable Cox and binomial regression models adjusted for relevant covariates. Among 861 women, 79 (9.2%) had vulvar cancer. Median follow-up was 49 months for OS and 40 months for PFS. Women with vulvar cancer were older and more often overweight. Five-year OS was 32% (95% CI, 19-46) in vulvar cancer versus 29% (95% CI, 25-34) in other cancers, adjusted HR 1.05 (95% CI, 0.75-1.46). Five-year PFS was 34% versus 29%, adjusted HR 0.96 (95% CI, 0.69-1.34). Major complications occurred in 33% vs 29%, adjusted RR 1.12 (95% CI, 0.77-1.58). Lymph node metastases, positive margins, and recurrent or persistent disease independently predicted poorer survival. Despite their older age, women with vulvar cancer had survival and morbidity comparable to those with other gynaecological malignancies. These findings support pelvic exenteration as a curative option for selected women with vulvar cancer when complete resection is feasible.

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.

Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of ESS, UTROSCT, and UUS with Prognostic Insights.

Low-grade endometrial stromal sarcomas (LG-ESS), high-grade ESS (HG-ESS), undifferentiated uterine sarcomas (UUS), and uterine tumors resembling ovarian sex cord tumors are distinct non-smooth muscle cell neoplasms with varying clinical outcomes, often exhibiting overlapping characteristics. Diagnosis can be supported by identifying characteristic recurrent translocations, which may be absent in some cases, complicating the distinction of equivocal cases. Additionally, cases with overlapping features of low-grade and high-grade characteristics are recognized. To address these challenges, we analyzed RNA-seq profiles of 262 cases. Our results revealed that LG-ESS, with and without recurrent fusions, clustered into 2 partially overlapping expression profiles associated with distinct overall and relapse-free survival outcomes, with the cluster containing a majority of fusion-negative tumors demonstrating better prognoses. uterine tumors resembling ovarian sex cord tumors expression profiles closely resembled those of both LG-ESS subgroups, with NCOA3 fusion-positive cases clustering in groups with better survival outcomes. Furthermore, a distinct cluster for HG-ESS with BCOR and YWHAE fusions was identified, differentiating these tumors from HG-ESS without fusions. ONECUT3 emerged as a potential specific marker for this HG-ESS-fusion entity. A significant expression overlap was observed between monomorphic HG-ESS without fusions and pleomorphic UUS. These samples separated further into 2 mixed clusters distinguished by differences in immune activity, which significantly influenced overall survival and relapse-free survival outcomes. Unsupervised clustering of UUS revealed subgroups resembling either HG-ESS or muscle-cell-differentiated tumors, suggesting that UUS may include poorly differentiated distinct entities, such as leiomyosarcoma, and that the distinction from HG-ESS may, in some cases, be arbitrary. Our transcriptome analysis highlights several entities with distinct survival characteristics, providing a foundation for further characterization of these rare, often difficult-to-classify, tumors.