Endometrial cancer is the most common gynecological malignancy in Europe, with a rising incidence due to increased age and obesity in the population.49 The majority of endometrial cancers (80%) are confined to the uterus at the time of diagnosis, since post-menopausal bleeding prompts investigations and early detection.12 Deep (≥50%) myometrial invasion, cervical stromal extension, non-endometrioid histology, high tumor grade and substantial (in contrast to focal) lymphovascular space invasion are independent risk factors for lymph node metastases and poor prognosis.81–83 The distribution of lymph node involvement is also prognostic as para-aortic lymph node metastases independently predict poor outcome.82 84 Since The Cancer Genome Atlas defined four molecular subgroups of endometrial cancers in 2013 (DNA polymerase ɛ ultramutated, POLEmut; DNA mismatch repair-deficient, MMRd; no specific molecular profile, NSMP; p53-abnormal, p53abn), molecular factors are increasingly being used to define groups at risk and guide adjuvant or systemic treatment.82 85 Among the four molecular subgroups p53abn cancers have the highest risk, while POLEmut have the lowest risk.86

The updated 2023 FIGO staging system for endometrial cancer includes histological types and tumor grading and also molecular subgroups if available, in order to better reflect the underlying biologic behavior of endometrial cancers.83 If POLEmut or p53abn is detected in early stage disease (former FIGO 2009 stage I) regardless of lymphovascular space invasion status or histologic type, the 2023 FIGO stage is changed to stage IAmPOLEmut or stage IICmp53abn, respectively.83 In addition, the 2023 FIGO staging system for endometrial cancer differentiates between synchronous ovarian cancers and metastatic ovarian lesions.83 Disease limited to the endometrium and ovaries in low-grade endometrioid carcinomas (stage IA3)(Figure 6) is distinguished from extensive spread of endometrial carcinoma to the ovary (stage IIIA1) (Figure 7) by the presence of the following criteria: (1) superficial (<50%) myometrial invasion; (2) absence of extensive/substantial lymphovascular space invasion; (3) no additional metastases; and (4) unilateral ovarian tumor limited to the ovary, without capsule invasion/rupture (equivalent to pT1a ovarian cancer). Low-grade endometrioid cancers involving both the endometrium and the ovary are considered to have good prognosis, and no adjuvant treatment is recommended, while metastatic ovarian involvement by endometrial carcinoma is associated with poor prognosis (Figures 6 and 7, Online Supplemental Videos S5 and 6).87 The changes incorporated in the 2023 FIGO staging system (Online Supplemental Appendix S4) should be consistent with the TNM classification, which should also be updated accordingly.

Synchronous endometrial and ovarian low-grade endometrioid cancer FIGO stage IA3 in a woman in her 30s who underwent transvaginal ultrasound, CECT, and FDG-PET-CT pre-operatively. Uterus with residual low-grade endometrial endometrioid cancer after hysteroscopic resection, with an intrauterine device in situ (A). Left ovary with unilocular-solid tumor histologically verified as low-grade endometrioid carcinoma; of note are papillary projections with smooth rounded contours, high perfusion on color Doppler and intracystic fluid with ground glass echogenicity (B). Pathologic lesion in the left ovary depicted on CECT (C) with contrast-enhancing solid components, and on PET-CT (D) with high FDG-avidity in the solid components; macroscopic appearance of the left ovary after oophorectomy (E, F). CECT, contrast-enhanced CT; FDG-PET-CT, 18F-fluorodeoxyglucose positron emission tomography combined with CECT. FIGO, International Federation of Gynecology and Obstetrics.The Online Supplemental Video S5 shows this case.

Transvaginal ultrasound (A–D), pelvic MRI (E–H), and abdominal CECT (I–L) in a woman in her 50 s diagnosed with clear cell endometrial cancer FIGO stage IIIA1. Transvaginal ultrasound depicts an isoechogenic uterine tumor infiltrating more than 50% of the myometrial wall (A); with protrusion but no invasion into the proximal endocervix, the distance from the external cervical os to the lower margin of the tumor is 22 mm (B); color Doppler depicts a moderately vascularized solid tumor of the right ovary (C); and a multilocular-solid tumor in the left ovary with moderately vascularized solid components (D). Pelvic MRI with T2-weighted sagittal (E) and T2/T1-weighted axial (G, H) series and DWI (high b-value image) (F) depicts a large, hyperintense mass in the uterus extending from the uterine fundus down to the cervix (E). The tumor exhibits restricted diffusion depicted as hyperintensity on the DWI image (F) with low apparent diffusion coefficient (ADC) value on the ADC map (not shown), indicating malignant tumor. On axial T2-weighted MRI small cysts are seen in the right ovarian tumor (G) as hyperintense regions in the anterior part. The left ovarian tumor depicted on T1-weighted MRI is hypointense due to cystic portion (H). Abdominal CECT depicts an irregular large uterine mass (I, K) and the right (I, K) and left (J, L) ovarian tumors with cystic lesions and contrast-enhancing septae. On axial CT at the level of the uterus (K) and at the level above the uterus (L) hypodense areas in the left ovary (L) and the right ovarian tumors (K) indicating cystic spaces. DWI, diffusion-weighted imaging; CECT, contrast-enhanced CT; FIGO, International Federation of Gynecology and Obstetrics. Online Supplemental Video S6 shows this case of endometrial cancer.

Ultrasound is the first-line imaging technique to evaluate endometrial pathology in cases of abnormal uterine bleeding and helps to triage patients for appropriate diagnostic tests. Transvaginal ultrasound plays a pivotal role in planning the management of women with abnormal uterine bleeding.6 88 The International Endometrial Tumor Analysis (IETA) group has been established to define the standardized terms, definitions, and measurements for description of sonographic features of the endometrium and uterine cavity (Online Supplemental Appendix S4).89 Based on a large amount of prospectively collected data, the IETA group defined easy-to-assess features, such as endometrial thickness <3 mm, three-layer pattern, and linear endometrial midline, all indicating low risk of endometrial cancer.90 Patients presenting with these features can be safely discharged with no further follow-up even with a history of abnormal uterine bleeding. Similarly, the presence of a single vessel without branching is associated with very low risk (1.5%) of endometrial cancer.90 For all other findings, further investigations and biopsy are recommended. The method of obtaining a histological sample (pipelle, curettage, or hysteroscopic resection under direct visualization) depends on the available resources and clinical experience. However, hysteroscopic biopsy is recommended (at least for focal lesions), since it yields higher agreement with final histological diagnosis.12 91–93

In histologically verified endometrial cancer, a trained sonographer can assess the size of the endometrial lesion (its anteroposterior diameter has key prognostic impact),94 depth of myometrial invasion, and cervical stromal invasion as well as screen for other pelvic pathology (Online Supplemental Appendix S4).12 27 95 Additionally, the identification of ultrasound features on gray-scale and power Doppler may be used to predict low-risk and high-risk endometrial cancer phenotypes (Online Supplemental Appendix S4).6 Unlike transabdominal ultrasound, transvaginal ultrasound is less limited by patient habitus (obesity) or position of the uterus.96 Ultrasound and MRI have similar accuracy in determining the local extent of endometrial cancer, although both methods may be inaccurate in 15–25% cases.88 97–103 A recent systematic review and meta-analysis from Alcázar et al confirmed very similar diagnostic performances of transvaginal ultrasound/MRI for detecting cervical stromal invasion, with reported pooled sensitivities and specificities of 69%/69% and specificities of 93%/91%, respectively.97 Another meta-analysis by the same authors found similar diagnostic performance of transvaginal ultrasound/MRI for detecting deep myometrial invasion, reporting pooled sensitivities and specificities of 75%/83% and 82%/82%, respectively.98 No statistical differences were found between ultrasound and MRI in local staging in both meta-analyses.97 98 Diagnostic performance for detecting deep myometrial invasion appears similar between expert and non-expert sonographers, whereas experts perform better in the evaluation of cervical stromal invasion.27 Thus, the training of sonographers in endometrial cancer staging is critical.

For local staging of endometrial cancer, pelvic MRI and transvaginal/transrectal ultrasound yield similar diagnostic performance, and the choice of imaging method is determined by local access to these imaging modalities and operator expertise.104 At some centers, transvaginal ultrasound is used as the first-line imaging tool, with subsequent selective use of pelvic MRI in cases with suboptimal assessment on ultrasound (eg, reduced acoustic visibility/penetration due to fibroids/bowel gas/obesity/other pathology). In other centers, pelvic MRI is used as the first-line imaging modality for pre-operative local staging.

Whole-body imaging can be considered in addition to pelvic ultrasound or MRI depending on the putative risk profile based on imaging findings, clinical features, and presence of pathologic factors, such as high tumor grade, substantial lymphovascular space invasion, non-endometrioid histology, p53abn molecular subgroup, tumor anteroposterior diameter >20 mm, deep (>50%) myometrial invasion, or cervical stroma infiltration.12 105–107 To predict high-risk cancers using ultrasound, the strategy of combining subjective assessment of cervical stromal invasion and myoinvasion with tumor grade correctly stratified 80% of patients as high-risk or low-risk cancer for the presence of lymph node metastases.108 Patients were classified as high risk based on biopsy-confirmed grade 3 endometrioid, gastrointestinal-type mucinous cancer or other non-endometrioid histotype and/or suspicion of deep myoinvasion or cervical stromal invasion on ultrasound. A similar approach was tested by Fasmer et al using pre-operative biopsy and pelvic MRI in all patients, with selective FDG-PET-CT based on high-risk MRI features (myoinvasion ≥50% and/or cervical stromal invasion and/or suspicious lymph nodes).109 Based on their findings, pre-operative FDG-PET-CT only in cases with high-risk MRI features seems to bring the most benefit in detecting distant spread while avoiding unnecessary FDG-PET-CT-related radiation in low-risk patients.

Both CECT and MRI are considered equivalent for the evaluation of nodal metastases, although neither can replace surgicopathologic lymph node assessment.104 FDG-PET-CT is considered the best imaging method to evaluate lymph node and distant metastases due to its high specificity, although sensitivity is lower.110 111 Due to limited sensitivity of imaging to detect small-volume metastases, surgical lymph node staging by sentinel lymph node biopsy remains important12 to allow the proper selection of adjuvant treatment and improve patient outcome.112

Local tumor extent, regional and distant lymph node metastases and other distant metastases should be documented by preoperative imaging using a standardized systematic checklist, including the use of schematic drawing(s) as appropriate (Online Supplemental Appendix S4).