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Simple Summary: Constant technological development of modern imaging has led to substantial improvement in management and decision-making in the diagnostic and prognostic process of many different neoplasms. This also applies to cervical cancer. The main evidence, providing the base of recently updated ESGO-ESTRO-ESP recommendations (2023) on the management and treatment of cervical cancer, has been evaluated and reviewed in this paper. Ultrasound has been suggested as a valid alternative to MRI in primary diagnostic workup of cervical cancer if performed by an expert sonographer. Additionally, CT or PET/CT exhibits a substantial role in assessing the extrapelvic spread of the disease in locally advanced cases or when suspicious lymph nodes are detected. The purpose of this article is to provide a comprehensive review of the role of different imaging techniques in staging settings, displaying a focused interest in the use of ultrasound. Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guidelines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ESGO-ESTRO-ESP recommendations was performed, further confirming this statement. Transvaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumor delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insufficient sensitivity to detect small-volume metastases, as in any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, contrast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography combined with CT (PET-CT) is recommended to assess extrapelvic spread. This paper aims to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Maximal-effort debulking surgery is the recommended approach for advanced-stage ovarian cancer. The role of imaging is to provide a preoperative systematic and structured report of tumour dissemination with special emphasis on key sites that preclude optimal resectability in ovarian cancer surgery. Imaging methods cannot reliably detect small volume carcinomatosis but yield high diagnostic performance for detecting bulky disease at critical sites for cytoreduction and can thus be reliably used to avoid unnecessary explorations. Although diagnostic laparoscopy may directly visualize intraperitoneal involvement, it has inherent limitations when investigating tumours behind the gastrosplenic ligament, in the lesser sac, mesenteric root or when exploring the retroperitoneum. The major benefit of laparoscopy appears as an ultimate triage step in situations where the imaging diagnosis is uncertain regarding resectability and the presence of diffuse small-volume carcinomatosis. Maximal-effort upfront or interval debulking surgery is the recommended approach for advanced-stage ovarian cancer. The role of diagnostic imaging is to provide a systematic and structured report on tumour dissemination with emphasis on key sites for resectability. Imaging methods, such as pelvic and abdominal ultrasound, contrast-enhanced computed tomography, whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography, yield high diagnostic performance for diagnosing bulky disease, but they are less accurate for depicting small-volume carcinomatosis, which may lead to unnecessary explorative laparotomies. Diagnostic laparoscopy, on the other hand, may directly visualize intraperitoneal involvement but has limitations in detecting tumours beyond the gastrosplenic ligament, in the lesser sac, mesenteric root or in the retroperitoneum. Laparoscopy has its place in combination with imaging in cases where ima-ging results regarding resectability are unclear. Different imaging models predicting tumour resectability have been developed as an adjunctional objective tool. Incorporating results from tumour quantitative analyses (e.g., radiomics), preoperative biopsies and biomarkers into predictive models may allow for more precise selection of patients eligible for extensive surgery. This review will discuss the ability of imaging and laparoscopy to predict non-resectable disease in patients with advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally. • The recurrence risk model in cervical cancer was composed of five prognostic factors. • The developed annual recurrence risk model (ARRM) stratifies the cohort into five significantly distinctive risk groups. • The ARRM represents a powerful tool for tailoring of appropriate surveillance strategy. • The ARRM can easily be used in routine clinical settings internationally. [ABSTRACT FROM AUTHOR]

Context.-- Ultrastaging of sentinel lymph nodes (SLNs) is a crucial aspect in the approach to SLN processing. No consensual protocol for pathologic ultrastaging has been approved by international societies to date. Objective.-- To provide a review of the ultrastaging protocol and all its aspects related to the processing of SLNs in patients with cervical cancer. Data Sources.-- In total, 127 publications reporting data from 9085 cases were identified in the literature. In 24% of studies, the information about SLN processing is entirely missing. No ultrastaging protocol was used in 7% of publications. When described, the differences in all aspects of SLN processing among the studies and institutions are substantial. This includes grossing of the SLN, which is not completely sliced and processed in almost 20% of studies. The reported protocols varied in all aspects of SLN processing, including the thickness of slices (range, 1-5 mm), the number of levels (range, 0--cut out until no tissue left), distance between the levels (range, 40-1000 μm), and number of sections per level (range, 1-5). Conclusions.-- We found substantial differences in protocols used for SLN pathologic ultrastaging, which can impact sensitivity for detection of micrometastases and even small macrometastases. Since the involvement of pelvic lymph nodes is the most important negative prognostic factor, such profound discrepancies influence the referral of patients to adjuvant radiotherapy and could potentially cause treatment failure. It is urgent that international societies agree on a consensual protocol before SLN biopsy without pelvic lymphadenectomy is introduced into routine clinical practice. [ABSTRACT FROM AUTHOR]

The criteria for distinction between independent primary tumors and metastasis from one site to the other in synchronous endometrioid endometrial and ovarian carcinoma (SEO) has been a matter of dispute for a long time. In our study we performed a comprehensive clinico-pathological and molecular analysis of 22 cases of SEO. Based on conventional clinico-pathological criteria the cases were classified as independent primary tumors (10 cases) and metastasis from one location to the other (12 cases). All tumors were analyzed by NGS with a panel of 73 genes (219 kbp). Clonal origin was confirmed in all cases by at least one shared mutation in PTEN, AKT1, PIK3CA, KRAS, TP53 and ARID1A. Two patients carried germline pathogenic mutation in cancer-predisposing genes BRCA1 or BARD1. Microsatellite instable phenotype was detected in 5/22 (22.7%) SEO, but in one case only in the endometrial tumor. In conclusion, our results showed that all 22 SEOs were clonally related, irrespectively of their clinico-pathological features. Even low grade and low stage tumors classified as independent primaries, according to the conventional morphological criteria, have a clonal origin. From the practical point of view, only the conventional morphological criteria should be used for the classification (staging) of these tumors. However, molecular profiling of these tumors may have prognostic and predictive meaning. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the diagnostic accuracy of subjective ultrasound evaluation of myometrial invasion of endometrial cancer and to compare its accuracy to objective methods. All consecutive patients with histologically proven endometrial cancer, who underwent ultrasound evaluation followed by surgical staging between January 2009 and December 2011, were prospectively enrolled. Myometrial invasion was evaluated by subjective assessment using ultrasound (<50% or ≥50%) and calculated as deepest invasion/normal myometrium ratio (Gordon’s ratio) and as tumor/uterine anteroposterior diameter ratio (Karlsson’s ratio). Histological assessment from hysterectomy was considered the gold standard. Altogether 210 patients were prospectively included. Subjective assessment and two objective ratios were found to be statistically significant predictors of the myometrial invasion (AUC = 0.65, p value < 0.001). Subjective assessment was confirmed as the most reliable method to assess myometrial invasion (79.3% sensitivity, 73.2% specificity, and 75.7% overall accuracy). Deepest invasion/normal myometrium (Gordon’s) ratio (cut-off 0.5) reached 69.6% sensitivity, 65.9% specificity, and 67.3% overall accuracy. Tumor/uterine anteroposterior diameter (Karlsson’s) ratio with the same cut-off reached 56.3% sensitivity, 76.4% specificity, and 68.1% overall accuracy. The subjective ultrasound evaluation of myometrial invasion performed better than objective methods in nearly all measures but showed statistically significantly better outcomes only in case of sensitivity. [ABSTRACT FROM AUTHOR]

Simple Summary: Lower-limb lymphedema (LLL) is a well-recognized adverse outcome of the surgical management of cervical cancer. Recently, sentinel lymph node (SLN) biopsy has emerged as an alternative procedure to systematic pelvic lymphadenectomy (PLND) aiming to decrease the risk of complications, especially LLL development. Our study represents the first prospective analysis of LLL incidence in cervical cancer patients after a uterine procedure with SLN biopsy, without systematic PLND. In an international multicenter trial SENTIX, the group of 150 patients was prospectively evaluated using both objective and subjective LLL assessments in 6 months intervals for 2 years. Contrary to the expectations, our results showed that SLN biopsy does not eliminate the risk of LLL development which occurred in a mild or moderate stage in about 26% of patients with a median interval to the onset of 9 months. Background: To prospectively assess LLL incidence among cervical cancer patients treated by uterine surgery complemented by SLN biopsy, without PLND. Methods: A prospective study in 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy. Objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. Results: The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10–19%), 9.2% for moderate LLL (LVI 20–39%), while only one patient (0.7%) developed severe LLL (LVI > 40%). The median interval to LLL onset was nine months. Transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. Conclusions: The replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed. [ABSTRACT FROM AUTHOR]

The data on the prognostic significance of low volume metastases in lymph nodes (LN) are inconsistent. The aim of this study was to retrospectively analyze the outcome of a large group of patients treated with sentinel lymph node (SLN) biopsy at a single referral center. Patients with cervical cancer, stage T1a-T2b, common tumor types, negative LN on preoperative staging, treated by primary surgery between 01/2007 and 12/2016, with at least unilateral SLN detection were included. Patients with abandoned radical surgery due to intraoperative SLN positivity detected by frozen section were excluded. All SLNs were postoperatively processed by an intensive protocol for pathological ultrastaging. Altogether, 226 patients were analyzed. Positive LN were detected in 38 (17%) cases; macrometastases (MAC), micrometastases (MIC), isolated tumor cells (ITC) in 14, 16, and 8 patients. With the median follow-up of 65 months, 22 recurrences occurred. Disease-free survival (DFS) reached 90% in the whole group, 93% in LN-negative cases, 89% in cases with MAC, 69% with MIC, and 87% with ITC. The presence of MIC in SLN was associated with significantly decreased DFS and OS. Patients with MIC and MAC should be managed similarly, and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: To revise FIGO staging of carcinoma of the cervix uteri, allowing incorporation of imaging and/or pathological findings, and clinical assessment of tumor size and disease extent.Methods: Review of literature and consensus view of the FIGO Gynecologic Oncology Committee and related societies and organizations.Results: In stage I, revision of the definition of microinvasion and lesion size as follows. Stage IA: lateral extension measurement is removed; stage IB has three subgroups-stage IB1: invasive carcinomas ≥5 mm and <2 cm in greatest diameter; stage IB2: tumors 2-4 cm; stage IB3: tumors ≥4 cm. Imaging or pathology findings may be used to assess retroperitoneal lymph nodes; if metastatic, the case is assigned stage IIIC; if only pelvic lymph nodes, the case is assigned stage IIIC1; if para-aortic nodes are involved, the case is assigned stage IIIC2. Notations 'r' and 'p' will indicate the method used to derive the stage-i.e., imaging or pathology, respectively-and should be recorded. Routine investigations and other methods (e.g., examination under anesthesia, cystoscopy, proctoscopy, etc.) are not mandatory and are to be recommended based on clinical findings and standard of care.Conclusion: The revised cervical cancer staging is applicable to all resource levels. Data collection and publication will inform future revisions. [ABSTRACT FROM AUTHOR]