Vincenzo Tarantino

Impact of surgery and molecular classification in stage IV endometrial cancer

Evidence supporting the role of surgery after neoadjuvant chemotherapy in advanced endometrial cancer remains limited. Additionally, the prognostic relevance of molecular classification in this setting is poorly defined. We aimed to evaluate overall survival in patients with peritoneal and/or extra-abdominal spread, focusing on surgical approach and molecular sub-type. We retrospectively analyzed all patients with Fédération Internationale de Gynécologie et d'Obstétrique 2009 stage IVB (Fédération Internationale de Gynécologie et d'Obstétrique 2023 IIIB2, IVB, IVC) endometrial cancer treated between January 2012 and September 2023. Patients were stratified according to immunohistochemistry-based molecular classification, intra-abdominal disease extension, and treatment strategy. Kaplan-Meier and Cox regression analyses were used to assess overall survival. Differences across groups were evaluated using appropriate nonparametric and categorical statistical tests. Among 363 eligible patients, 229 (63.1%) underwent primary cytoreduction, 52 (14.3%) had interval debulking surgery, 55 (15.2%) received chemotherapy alone, and 27 (7.4%) were untreated. Patients receiving neoadjuvant or exclusive chemotherapy more frequently had extra-abdominal (p < .001) and upper abdominal disease (p < .001). In patients with extra-pelvic disease, overall survival was comparable between primary and interval surgery (p = .82). Among those treated with neoadjuvant treatment, surgical cytoreduction was strongly associated with improved overall survival (p < .001). Mismatch repair-deficient patients had better overall survival than those with p53 abnormal tumors (34 vs 21 months, p = .026). No specific molecular profile-estrogen receptor positive tumors showed longer overall survival than both p53 abnormal and no specific molecular profile-estrogen receptor negative sub-types (60 vs 34 and 21 months, p = .018 and p = .041, respectively). In multivariate analysis, extra-pelvic disease (p = .042) and exclusive chemotherapy (p < .0001) were independent negative prognostic factors. In advanced endometrial cancer, surgery remains a key component of management. Our findings suggest a potential survival advantage for patients who undergo surgery-either as primary treatment or following neoadjuvant chemotherapy-compared to those treated with chemotherapy alone. Molecular classification may offer prognostic insight even in stage IV disease, although further validation is required. These findings provide a benchmark for future studies in the evolving landscape of immunotherapy and personalized treatment.

ENDOESTRO score: Where is the dark side? Evaluation of estrogen receptor expression cutoff in endometrial cancer molecular classification, an ambispective study

Estrogen receptor (ER) expression has prognostic value in endometrial cancer (EC), also in the context of molecular classification. However, a standardized cutoff to define ER positivity is lacking. To identify the ER expression cutoff that best correlates with survival outcomes overall and within each molecular subgroup. We conducted an ambispective study comprising a retrospective phase (Feb 2017-Feb 2022) and a prospective phase (Mar 2022-Jan 2024), including patients with EC who underwent surgery at our institution. In the retrospective cohort, molecular subgroups were defined by immunohistochemistry (IHC): 1) MMRp Among 2084 patients, ER < 10 % was the strongest cutoff for prognosis based on disease-free survival (DFS). Patients with ER < 10 % and < 1 % shared similar unfavorable clinicopathological and molecular features, while ER ≥ 10 % was associated with more favorable profiles. ER < 10 % was an independent adverse prognostic factor in uni- and multivariate analyses for DFS and overall survival, particularly in MMRp ER < 10 % expression is a robust prognostic indicator, associated with worse outcomes and may serve as a clinically meaningful cutoff in endometrial cancer risk stratification. Further prospective validation is warranted.

Exploring isolated tumor cells entity in endometrial cancer

Endometrial cancer (EC) management includes nodal staging and molecular classification. Despite molecular advancements, the biological significance of isolated tumor cells (ITC) in EC remains unclear. This study aimed to characterize ITC in the context of pathological and molecular features MATERIALS AND METHODS: A multicenter, retrospective analysis included EC patients diagnosed between June 2018 and May 2024 who underwent surgical staging via sentinel lymph node (SLN) biopsy and molecular profiling. ITC cases detected through SLN ultrastaging or One Step Nucleic Acid Amplification (OSNA) were compared with N0 and N + (micro-/macrometastasis) groups. Among the 1821 patients included, nodal status was N0 in 84.5 %, ITC in 5.1 %, micrometastases in 5.3 %, and macrometastases in 4.5 %. ITC patients exhibited deep myometrial invasion in 67.7 % of cases vs. 28.7 % in N0 (p < 0.001). Diffuse lymphovascular space invasion (LVSI) was significantly higher in ITC (52.1 %) than N0 (12.2 %, p < 0.001). MMR deficiency was more frequent in ITC (33.3 %) vs. N0 (25.0 %, p = 0.07). POLE mutations were more common in N0 (4.2 %) and ITC (3.1 %) vs. N + (1.1 %), though not statistically significant. p53-abnormal tumors were significantly associated with N + status (19.4 %) compared to ITC (7.3 %, OR 0.33, p = 0.008). No relapses occurred among ITC patients with low-risk features. These findings suggest that ITC may represent an early form of nodal involvement, biologically distinct from micro- and macrometastases. The association with MMR deficiency and the absence of aggressive markers such as p53 abnormalities support a less aggressive profile. Integrating molecular and pathological features may refine risk stratification and inform management strategies for EC patients with ITC.

Innovations in laparoscopic management of endometrial cancer

Endometrial cancer is one of the most common gynecologic malignancies, with increasing incidence, in developed countries. Advances in minimally invasive surgery, particularly laparoscopic with or without the use of computer-assisted ('robotic') platforms, have transformed its management, improving surgical outcomes and patient recovery. This review explores recent innovations in laparoscopic management of endometrial cancer, including robotic-assisted laparoscopic surgery, sentinel lymph node mapping, and the integration of artificial intelligence in surgical navigation. A comprehensive literature search was conducted using PubMed and clinical trial databases to assess the impact of these advancements on surgical precision, oncologic outcomes, and patient recovery. Major studies comparing robotic-assisted laparoscopy, traditional laparoscopy, and open surgery are reviewed, along with new technologies that support real-time decision-making during surgery. Minimally invasive approaches have become the standard of care for early-stage endometrial cancer, offering superior perioperative outcomes. While robotic-assisted surgery provides technical advantages, cost and accessibility remain challenges. Sentinel lymph node mapping reduces morbidity compared to full lymphadenectomy, and artificial intelligence holds promise in optimizing surgical precision. Future research should focus on refining these technologies, improving patient selection criteria, and ensuring equitable access to advanced surgical techniques.

Comparison of Different Near-Infrared Technologies to Detect Sentinel Lymph Node in Uterine Cancer: A Prospective Comparative Cohort Study

Objectives: Sentinel lymph node biopsy is considered a crucial step in endometrial cancer staging. Cervical injection has become the most favored technique and indocyanine green has been demonstrated to be more accurate than other tracers. Different near-infrared camera systems are currently being used to detect indocyanine green in sentinel lymph nodes and have been compared in different patients. The present study aimed to determine the number and site of sentinel lymph nodes detected in the same patients with two different near-infrared technologies. Methods: This is a prospective, single-center, observational, non-sponsored study. Patients with presumed uterine-confined endometrial cancer were prospectively enrolled. After cervical injection, two different near-infrared cameras were used to detect sentinel lymph nodes at the same time: Olympus, Tokyo, Japan—considered the standard (SNIR); and Medtronic, Minneapolis, MN, USA with VISION SENSE® which is a new laser near-infrared (LNIR) fluorescence laparoscope. The two cameras were alternatively switched on to detect sentinel lymph nodes in the same patients. Results: Seventy-four consecutive patients were included in the study. Most of the patients were diagnosed with endometrioid histology (62, 83.8%), FIGO stage IA (48, 64.9%), grade 2 (43, 58.1%), and underwent surgery with laparoscopic approach (70, 94.0%). The bilateral detection rate was 56/74 (75.7%) with SNIR and 63/74 (85.1%) with LNIR (p = 0.214). The total number of sentinel lymph nodes identified in the left hemipelvis was 65 and 70 with SNIR and LNIR, respectively; while in the right hemipelvis, there were 74 and 76, respectively. The median number of sentinel lymph nodes identified with SNIR and LNIR was 2 (range, 0–4) and 2 (range, 0–4), respectively (p = 0.370). No difference in site of sentinel lymph node detection was evident between the two technologies (p = 0.994). Twelve patients (16.2%) had sentinel lymph node metastasis: in all cases metastatic sentinel lymph nodes were detected both with Olympus and LNIR. Conclusions: No difference in bilateral detection rate and number or site of sentinel lymph node detection was evident comparing two different technologies of near-infrared camera for ICG detection in endometrial cancer patients. No difference in sentinel lymph node metastases identification was detected between the two technologies.

Multi-center, international endometrial cancer consortium highlights

The multi-center, international consortium on endometrial cancer held in January 2025 at Mayo Clinic in Rochester, Minnesota brought together leading experts in gynecologic oncology to explore the latest advancements in the understanding, diagnosis, and treatment of endometrial cancer. Discussions centered on key topics, including updates in molecular testing and disease staging, emerging treatment strategies for advanced and recurrent disease, fertility-sparing management, and critical pathology challenges, particularly, the assessment of lympho-vascular space invasion. Each topic was examined in dedicated working group sessions, fostering in-depth exchanges to identify research priorities and develop actionable strategies. This summary highlights the central themes and insights from the meeting, outlining a roadmap for future advancements in the field. By promoting inter-disciplinary collaboration, the meeting laid the foundation for future research, policy recommendations, and clinical innovations aimed at improving patient outcomes.