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The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond.

In 2023, based on advances in the understanding of the pathological and molecular features of endometrial carcinoma, an updated International Federation of Gynaecology and Obstetrics (FIGO) staging system was published, aiming to better define prognostic groups and identify relevant treatment subgroups by including factors reflecting tumour biology (histological subtypes, lymphovascular space invasion, and molecular classification) alongside refinements of anatomical factors (peritoneal carcinomatosis and lymph node metastasis). As part of its mission to improve the quality of care for people with gynaecological cancers, the European Society of Gynaecological Oncology (ESGO), European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) updated the ESGO–ESTRO–ESP evidence-based guidelines published in 2021 by incorporating this revised FIGO staging and the large body of new evidence addressing the management of endometrial carcinoma. The development process of these guidelines was based on a systematic literature review and critical appraisal process involving an international multidisciplinary development group consisting of 30 experts from relevant disciplines (gynaecological oncology, radiation oncology, medical oncology, and pathology). A patient representative was also included. Before publication, the guidelines were reviewed by 225 independent international practitioners in cancer care delivery and three patient representatives from Asia, Europe, North Africa, North America, the Middle East, and South America to ensure a global perspective. These guidelines comprehensively cover diagnosis, management, follow-up, and patient education. Management includes surgical and adjuvant therapy according to the stage of the disease, and metastatic and recurrent disease. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

Purpose To investigate whether qualitative magnetic resonance (MR) features can distinguish leiomyosarcoma (LMS) from atypical leiomyoma (ALM) and assess the feasibility of texture analysis (TA). Methods This retrospective study included 41 women (ALM = 22, LMS = 19) imaged with MRI prior to surgery. Two readers (R1, R2) evaluated each lesion for qualitative MR features. Associations between MR features and LMS were evaluated with Fisher’s exact test. Accuracy measures were calculated for the four most significant features. TA was performed for 24 patients (ALM = 14, LMS = 10) with uniform imaging following lesion segmentation on axial T2-weighted images. Texture features were pre-selected using Wilcoxon signed-rank test with Bonferroni correction and analyzed with unsupervised clustering to separate LMS from ALM. Results Four qualitative MR features most strongly associated with LMS were nodular borders, haemorrhage, “T2 dark” area(s), and central unenhanced area(s) (p ≤ 0.0001 each feature/reader). The highest sensitivity [1.00 (95%CI:0.82-1.00)/0.95 (95%CI: 0.74-1.00)] and specificity [0.95 (95%CI:0.77-1.00)/1.00 (95%CI:0.85-1.00)] were achieved for R1/R2, respectively, when a lesion had ≥3 of these four features. Sixteen texture features differed significantly between LMS and ALM (p-values: <0.001-0.036). Unsupervised clustering achieved accuracy of 0.75 (sensitivity: 0.70; specificity: 0.79). Conclusions Combination of ≥3 qualitative MR features accurately distinguished LMS from ALM. TA was feasible. Key Points • Four qualitative MR features demonstrated the strongest statistical association with LMS . • Combination of ≥3 these features could accurately differentiate LMS from ALM . • Texture analysis was a feasible semi-automated approach for lesion categorization .

Anti‐HER2 therapy is indicated for erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐amplified/overexpressing endometrial carcinoma (EC). Mutations constitute another mode of ERBB2 activation, but only rare ERBB2‐mutated ECs have been reported. We sought to characterize the clinicopathologic and genetic features of ERBB2‐mutated EC. From an institutional cohort of 2638 ECs subjected to clinical tumor‐normal panel sequencing, 69 (2.6%) with pathogenic ERBB2 mutation(s) were identified, of which 11 were also ERBB2‐amplified. The most frequent ERBB2 hotspot mutations were V842I (38%) and R678Q (25%). ERBB2 mutations were clonal in 87% of evaluable cases. Immunohistochemistry revealed low HER2 protein expression in most ERBB2‐mutated ECs (0/1+ in 66%, 2+ in 27%); all 3+ tumors (7.3%) were also ERBB2‐amplified. Compared to ERBB2‐wildtype ECs (with or without ERBB2 amplification), ERBB2‐mutated/non‐amplified ECs were enriched for the microsatellite instability‐high (MSI‐H) and, to a lesser extent, DNA polymerase epsilon, catalytic subunit (POLE) molecular subtypes, and associated with high tumor mutational burden and low chromosomal instability. Survival outcomes were similar between patients with ERBB2‐mutated/non‐amplified versus wildtype EC, whereas ERBB2 amplification was associated with worse prognosis on univariate, but not multivariate, analyses. In conclusion, ERBB2 mutation defines a rare subgroup of ECs that is pathogenically distinct from ERBB2‐wildtype and ERBB2‐amplified ECs. ERBB2 amplification is a known driver of copy number‐high/TP53‐abnormal high‐grade endometrial carcinoma and is associated with HER2 overexpression. In this retrospective cohort of clinically annotated endometrial carcinomas, ERBB2 pathogenic mutations define a distinct and non‐overlapping subgroup of tumors, typically with low levels of HER2 expression, high tumor mutational burden, microsatellite instability‐high status, and low‐grade endometrioid histology.

After the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer. Recent studies assessed the role of a non-radical approach in low risk cervical cancer and showed no survival difference compared with radical hysterectomy. However, there is a gap in knowledge regarding the oncologic outcomes of minimally invasive simple hysterectomy in low risk cervical cancer. This review offers an overview of the current evidence on the role of the minimally invasive approach in low risk cervical cancer and raises the need for a new clinical trial in this setting.

Background One of the most important principles in modern cervical cancer surgery is the concept of tailoring surgical radicality. In practice, this means abandoning the “one-fits-all” concept in favor of tailored operations. The term “radical hysterectomy” is used to describe many different procedures, each with a different degree of radicality. Anatomic structures are subjected to artificial dissection artifacts, as well as different interpretations and nomenclatures. This study aimed to refine and standardize the principles and descriptions of the different classes of radical hysterectomy as defined in the Querleu–Morrow classification and to propose its universal applicability. Methods All three authors independently examined the current literature and undertook a critical assessment of the original classification. Images and pathologic slides demonstrating different types of radical hysterectomy were examined to document a consensual vision of the anatomy. The Cibula 3-D concept also was included in this update. Results The Querleu–Morrow classification is based on the lateral extent of resection. Four types of radical hysterectomy are described, including a limited number of subtypes when necessary. Two major objectives remain constant: excision of central tumor with clear margins and removal of any potential sites of nodal metastasis. Conclusion Studies evaluating radicality in the surgical management of cervical cancer should be based on precise, universally accepted descriptions. The authors’ updated classification presents standardized, universally applicable descriptions of different types of hysterectomies performed worldwide, categorized according to degree of radicality, independently of theoretical considerations.

Metaplastic breast carcinoma (MBC) and uterine carcinosarcoma (UCS) are rare aggressive cancers, characterized by an admixture of adenocarcinoma and areas displaying mesenchymal/sarcomatoid differentiation. In this study, we investigate whether MBCs and UCSs harbor similar patterns of genetic alterations and mutational signatures using whole‐exome sequencing data. In addition, we examine whether the different histologic components of MBCs and UCSs are clonally related. Metaplastic breast carcinoma (MBC) and uterine carcinosarcoma (UCS) are rare aggressive cancers, characterized by an admixture of adenocarcinoma and areas displaying mesenchymal/sarcomatoid differentiation. We sought to define whether MBCs and UCSs harbor similar patterns of genetic alterations, and whether the different histologic components of MBCs and UCSs are clonally related. Whole‐exome sequencing (WES) data from MBCs (n = 35) and UCSs (n = 57, The Cancer Genome Atlas) were reanalyzed to define somatic genetic alterations, altered signaling pathways, mutational signatures, and genomic features of homologous recombination DNA repair deficiency (HRD). In addition, the carcinomatous and sarcomatous components of an additional cohort of MBCs (n = 11) and UCSs (n = 6) were microdissected separately and subjected to WES, and their clonal relatedness was assessed. MBCs and UCSs harbored recurrent genetic alterations affecting TP53, PIK3CA, and PTEN, similar patterns of gene copy number alterations, and an enrichment in alterations affecting the epithelial‐to‐mesenchymal transition (EMT)‐related Wnt and Notch signaling pathways. Differences were observed, however, including a significantly higher prevalence of FAT3 and FAT1 somatic mutations in MBCs compared to UCSs, and conversely, UCSs significantly more frequently harbored somatic mutations affecting FBXW7 and PPP2R1A as well as HER2 amplification than MBCs. Genomic features of HRD and biallelic alterations affecting bona fide HRD‐related genes were found to be more prevalent in MBCs than in UCSs. The distinct histologic components of MBCs and UCSs were clonally related in all cases, with the sarcoma component likely stemming from a minor subclone of the carcinoma component in the samples with interpretable chronology of clonal evolution. Despite the similar histologic features and pathways affected by genetic alterations, UCSs differ from MBCs on the basis of FBXW7 and PPP2R1A mutations, HER2 amplification, and lack of HRD, supporting the notion that these entities are more than mere phenocopies of the same tumor type in different anatomical sites.

IntroductionSentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance.MethodsA Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability.ResultsSeventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88).ConclusionSpecific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

Purpose The aim of this study was to characterize treatment patterns and oncologic outcomes in patients with low-volume lymph node metastasis (isolated tumor cells [ITCs] and micrometastasis [MM]) discovered during sentinel lymph node (SLN) mapping for endometrial carcinoma. Methods We identified endometrial cancer cases treated surgically from September 2005 to April 2013 in which SLN mapping was performed. MM was defined as tumor within a lymph node measuring >0.2 mm but <2.0 mm, and ITCs were those measuring ≤0.2 mm. Results Overall, 844 patients, with a median age of 61 years (range 30–90), met the inclusion criteria. Histology was as follows: endometrioid, 724 (85.8 %) patients; serous, 104 (12.3 %) patients; and clear cell, 16 (1.9 %) patients. The median number of lymph nodes resected was six (range 0–60), and the median number of SLNs was two (range 0–15). Overall, 753 (89.2 %) patients were node-negative, 23 (2.7 %) had ITCs only, 21 (2.5 %) had MM only, and 47 (5.6 %) had macrometastasis. Adjuvant chemotherapy was administered to 106 (14 %) of 753 node-negative patients, 19 (83 %) of 23 patients with ITCs, 17 (81 %) of 21 patients with MM, and 42 (89 %) of 47 with macrometastasis. Median follow-up was 26 months (range 0–108). Three-year recurrence-free survival was as follows: node-negative patients, 90 % (±1.5); ITCs only, 86 % (±9.4); MM only, 86 % (±9.7); and macrometastasis, 71 % (±7.2) [ p  < 0.001]. Conclusions Patients with ITCs and MM frequently received adjuvant chemotherapy and had improved oncologic outcomes in comparison to those with macrometastasis to the lymph nodes. Further prospective study is needed to determine optimal post-resection management in patients with ITCs or MM alone.

To evaluate whether radiomic features from contrast-enhanced computed tomography (CE-CT) can identify DNA mismatch repair deficient (MMR-D) and/or tumor mutational burden-high (TMB-H) endometrial cancers (ECs). Patients who underwent targeted massively parallel sequencing of primary ECs between 2014 and 2018 and preoperative CE-CT were included (n = 150). Molecular subtypes of EC were assigned using DNA polymerase epsilon ( POLE ) hotspot mutations and immunohistochemistry-based p53 and MMR protein expression. TMB was derived from sequencing, with > 15.5 mutations-per-megabase as a cut-point to define TMB-H tumors. After radiomic feature extraction and selection, radiomic features and clinical variables were processed with the recursive feature elimination random forest classifier. Classification models constructed using the training dataset (n = 105) were then validated on the holdout test dataset (n = 45). Integrated radiomic-clinical classification distinguished MMR-D from copy number (CN)-low-like and CN-high-like ECs with an area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI 0.58–0.91). The model further differentiated TMB-H from TMB-low (TMB-L) tumors with an AUROC of 0.87 (95% CI 0.73–0.95). Peritumoral-rim radiomic features were most relevant to both classifications (p ≤ 0.044). Radiomic analysis achieved moderate accuracy in identifying MMR-D and TMB-H ECs directly from CE-CT. Radiomics may provide an adjunct tool to molecular profiling, especially given its potential advantage in the setting of intratumor heterogeneity.