Richard Tóth

Sentinel SENECA risk factors for unsuccessful bi-lateral sentinel lymph node mapping in endometrial cancer

Our study aims to assess the risk factors associated with bi-lateral sentinel lymph node (SLN) mapping failure in endometrial cancer. The SENECA study was a retrospective multi-center international observational study that reviewed data from 2139 women with clinical stage I-to-II endometrial cancer across 64 centers in 17 countries. Between January 2021 and December 2022, patients underwent surgical treatment with SLN assessment, following the guidelines of the European Society of Gynaecological Oncology. Risk factors associated with the absence of bi-lateral mapping were analyzed using χ Among the 2139 patients, the bi-lateral lymph node detection rate was 82.7%, whereas the unilateral detection rate was 97.3%. In multi-variate analysis, 5 risk factors remained statistically associated with unsuccessful bi-lateral lymph node mapping: high-grade histology (OR 1.35, 95% CI 1.02 to 1.79, p=.03), myometrial invasion >50% (OR 1.37, 95% CI 1.07 to 1.75, p=.012), low-volume surgeon <20 cases/year (OR 2.11, 95% CI 1.55 to 2.89, p<.01), open surgical approach (OR 1.72, 95% CI 1.06 to 2.78 , p=.03), and non-indocyanine green tracer (OR 4.59, 95% CI 2.64 to 7.99, p<.01). The addition of bi-lateral pelvic lymphadenectomy and/or paraaortic lymphadenectomy to SLN biopsy caused an increased rate of intra-operative complications (2% vs 8.4%, p<.01) and all-grade post-operative complications (4.1% vs 11.2%, p<.01). Our study identifies 5 risk factors associated with unsuccessful lymph node mapping in endometrial cancer. Efforts should be made to perform this technique with indocyanine green, through minimally invasive surgery, and performed or supervised by an experienced surgeon with ≥20 endometrial cancer cases per year.

Systemic Inflammatory Indices—Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)—As Potential Rule-Out Biomarkers for Invasive Cervical Carcinoma

Cervical cancer, primarily caused by high-risk Human Papilloma Virus (HPV), remains a global health concern. Prognostic biomarkers reflecting systemic inflammation and immune response—the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI)—have recently attracted interest for their potential predictive value in cervical cancer. We conducted a retrospective observational study including 344 patients who underwent loop electrosurgical excision of cervical intraepithelial neoplasia at Semmelweis University, Budapest, Hungary, between 2021 and 2024. Demographic, cytologic, histologic, and laboratory data were collected, and SII and SIRI were calculated. Statistical analyses, including Receiver Operating Characteristic (ROC) analyses, were performed. Higher SII and SIRI values were significantly associated with higher-grade lesions and invasive carcinoma. ROC analyses indicated good discriminatory performance, with negative predictive values of 96–100%, suggesting potential utility in ruling out malignant transformation. SII and SIRI are simple, cost-effective, and minimally invasive biomarkers that correlate with lesion severity in cervical disease. Their high negative predictive value supports a potential role as complementary rule-out tools in diagnostic evaluation. Further prospective studies are needed to validate these findings and to define clinically meaningful cut-off values for routine use.

Declaration on cervical cancer elimination: literature review and perspectives from early-career clinicians.

Despite effective prevention methods, cervical cancer remains one of the most incident malignancies globally. This literature review and perspectives from early-career clinicians aim to propose actionable recommendations to reduce the global burden of cervical cancer. The authors, representing the early-career clinicians and researchers, patient representatives, epidemiologists, and gynecologic oncology experts, identified 5 key pillars for cervical cancer elimination based on literature reviews and interdisciplinary discussion: (1) raising awareness of human papillomavirus (HPV) and cervical cancer; (2) ensuring evidence-based HPV communication; (3) fostering collaboration with other specialties and organizations; (4) increasing HPV vaccination rates; and (5) improving cervical cancer screening. Achieving the World Health Organization's cervical cancer elimination target by 2030 requires a comprehensive, multi-faceted approach. Our recommendations emphasize the need for targeted awareness campaigns, evidence-based communication, collaboration with various stakeholders, promotion of best practices, and keeping evidence of innovative interventions up-to-date, with intensified efforts in low- and middle-income countries where the burden is the greatest.

Global survey on training and practice in sentinel lymph node mapping for endometrial and cervical cancer among early-career gynecologic oncologists

This survey was designed to evaluate exposure to sentinel mapping for cervical and endometrial cancers in addition to the quality and availability of surgical training in sentinel procedures around the world. Furthermore, we aimed to identify obstacles in surgical training in the sentinel procedure to support the adoption of this technique in clinical practice. A 52-item survey was developed and computed using Qualtrics XM and SurveyMonkey software. The target population were members of the European Society of Gynaecological Oncology and the International Gynecological Cancer Society aged ≤40 years. The study invitation was disseminated within both organizations' database. The survey hyperlink was active between September and December 2022. Respondents using the same Internet Protocol address were excluded to avoid duplication of responses. Responses to <50% questions were excluded. Overall, 238 respondents joined the survey, and 182 (76.5%) provided answers that met the inclusion criteria. Sentinel mapping was implemented for a longer period and used more frequently in endometrial than in cervical carcinoma; 55% of the responders were initially trained in systematic lymph node dissection, and 22% were not yet trained in any lymph node staging. The main challenges in applying sentinel procedure for early-career gynecologic oncologists were no access to hands-on training (n = 22, 12.1%) and no clinical routine in performing systematic pelvic (n = 15, 8.2%) and para-aortic (n = 35, 19.2%) lymph node dissection in case of failed mapping. Although sentinel lymph node biopsy is integrated in cervical and endometrial cancer guidelines, a significant number of institutions do not implement this procedure in clinical routine, and 22% of early-career gynecologic oncologists are not trained in any type of surgical lymph node staging. Support for sentinel mapping in national guidelines and guided training opportunities are needed to apply this method globally.

SENECA study: staging endometrial cancer based on molecular classification

Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.