Andrea Rosati

Concurrent endometrial cancer in atypical endometrial hyperplasia and the role of sentinel lymph nodes: clinical insights from a multicenter experience

This study aimed to evaluate the prevalence of concurrent endometrial cancer in patients pre-operatively diagnosed with atypical endometrial hyperplasia undergoing hysterectomy. Additionally, we assessed the occurrence of high to intermediate-risk and high-risk tumors according to the ESGO-ESTRO-ESP classification. The study also compared surgical outcomes and complications between patients undergoing simple hysterectomy and those undergoing hysterectomy with sentinel lymph node biopsy. In this multicenter retrospective study, patients with a pre-operative diagnosis of atypical endometrial hyperplasia were identified and divided into two groups: Group 1, which included patients treated with total hysterectomy with or without bilateral salpingo-oophorectomy, and Group 2, where sentinel lymph node biopsy was incorporated into the standard surgical treatment. Among 460 patients with atypical endometrial hyperplasia, 192 received standard surgical management (Group 1) and 268 underwent sentinel lymph node biopsy (Group 2). A total of 47.2% (95% CI 42.6% to 51.7%) of patients were upgraded to endometrial cancer on final histopathological examination. High to intermediate-risk and high-risk tumors constituted 12.3% and 9.2% in Group 2 and 7.4% and 3.7% in Group 1. Lymph node metastases were identified in 7.6% of patients with concurrent endometrial cancer who underwent nodal assessment with at least unilateral mapping. Of the 12 sentinel lymph node metastases, 75.0% were micrometastases, 16.7% macrometastases, and 8.3% isolated tumor cells. No significant differences were found in estimated blood loss, operative time, and intra-operative and post-operative complications between the two groups. The rate of patients undergoing sentinel lymph node biopsy doubled every 2 years (OR 2.010, p<0.001), reaching 79.1% in the last 2 years. This study found a prevalence of concurrent endometrial cancer of 47.2%, and sentinel lymph node biopsy provided prognostic and therapeutic information in 60.8% of cases. It also allowed for the adjustment of adjuvant therapy in 12.3% of high to intermediate-risk patients without increasing operative time or complication rates.

Cardiophrenic lymph nodes in advanced ovarian cancer

Epithelial ovarian cancer most commonly presents at advanced stages, and prognosis is influenced by residual disease following cytoreduction. The significance of cardiophrenic lymph node resection at the time of cytoreductive surgery in advanced ovarian cancer remains a topic of debate. Enlarged cardiophrenic lymph nodes are detected through high-resolution imaging; however, the optimal imaging technique in determining feasibility of node resection remains uncertain. Similarly, the impact of excision of cardiophrenic lymph nodes on progression-free and overall survival remains elusive. The indications for resection of cardiophrenic lymph nodes are not addressed in standard ovarian cancer guidelines. Patients with cardiophrenic lymph nodes exceeding 1 cm in size may be considered for resection if complete intra-abdominal cytoreduction is feasible to no gross residual. The surgical approach might be either by open access or by video-assisted thoracoscopic surgery (minimally invasive approach), and major complications following cardiophrenic lymph nodes resection are low. Pathological cardiophrenic lymph nodes are associated with a poorer overall prognosis and can serve as a prognostic parameter; however, the therapeutic benefit of cardiophrenic lymph nodes resection remains inconclusive.

Pattern of recurrence in endometrial cancer. The murderer always returns to the scene of the crime

Endometrial cancer recurrence occurs in about 18 % of patients. This study aims to analyze the pattern recurrence of endometrial cancer and the relationship between the initial site of primary disease and the relapse site in patients undergoing surgical treatment. We retrospectively reviewed all surgically treated patients with endometrial cancer selecting those with recurrence. We defined primary site disease as uterus, lymph nodes, or peritoneum according to pathology analysis of the surgical specimen. The site of recurrence was defined as vaginal cuff, lymph nodes, peritoneum, and parenchymatous organs. Our primary endpoint was to correlate the site of initial disease with the site of recurrence. The study enrolled 1416 patients. The overall recurrence rate was 17,5 % with 248 relapses included in the study. An increase of 9.9, 5.7, and 5.7 times in the odds of relapse on the lymph node, peritoneum, and abdominal parenchymatous sites respectively was observed in case of nodal initial disease (p < 0.001). A not significant difference in odds was observed in terms of vaginal cuff relapse (OR 0.9) between lymph node ad uterine primary disease (p = 0.78). An increasing OR of 8.7 times for nodal recurrences, 46.6 times for peritoneum, and 23.3 times for parenchymatous abdominal recurrences were found in the case of primary peritoneal disease (p < 0.001). Endometrial cancer tends to recur at the initial site of the disease. Intraoperative inspection of the adjacent sites of primary disease and targeted instrumental examination of the initial sites of disease during follow-up are strongly recommended.

MIRaGE (Minimally Invasive suRGery in recurrent Endometrial cancer)

Endometrial cancer is one of the most common gynecologic malignancies. Recurrence occurs in 10% to 15% of early-stage and up to 70% of advanced-stage cases. Secondary cytoreductive surgery is critical when complete gross resection is achievable. Minimally invasive surgery may offer perioperative advantages, but data on patient selection and oncologic outcomes are limited. This retrospective study included patients with first abdominal recurrence of endometrial cancer who underwent secondary cytoreductive surgery at Fondazione Policlinico Universitario A. Gemelli IRCCS between 2010 and 2023. Patients were grouped by surgical approach (minimally invasive surgery [MIS]: laparoscopy/robotic-assisted vs open surgery). The primary endpoint was the identification of clinical and radiological preoperative predictors of successful MIS, defined as complete gross resection. Secondary endpoints included intraoperative and perioperative outcomes, and survival outcomes (overall survival and progression-free survival). Among 192 patients with abdominal recurrence, 74 (38.5%) underwent MIS. The 2 groups were not fully homogeneous, differing mainly in relapse site and recurrence pattern; nevertheless, complete gross resection was achieved in 97.3% of minimally invasive procedures and 94.9% of open surgeries (p = .42). Minimally invasive surgery was associated with lower blood loss (p < .001), fewer transfusions (p = .030), shorter operative times (p < .001), and reduced hospital stays (p < .001). Independent predictors of successful MIS were body mass index ≥30, early-stage disease, single-site relapse, and loco-regional or lymph-node recurrence. No significant differences were observed in survival outcomes, with comparable overall survival (p = .47) and progression-free survival (p = .43) between groups. Minimally invasive surgery may represent a feasible option for selected patients with recurrent endometrial cancer, providing perioperative advantages with comparable survival outcomes. Prospective multicenter studies are needed to confirm oncologic safety and to refine patient selection, also in the context of integration with novel therapies.

Major determinants of survival in recurrent endometrial cancer—the role of secondary cytoreductive surgery: a multicenter study

The main objective of the study was to assess the influence of different clinical and therapeutic variables on the oncological outcomes of patients with endometrial cancer relapse. In particular, we evaluated the impact of cytoreductive surgery with the achievement of complete gross resection. This is a multicenter retrospective cohort study conducted in three centers in Italy and including all patients with first relapse of endometrial cancer from January 2010 to December 2021. Data from 331 women with recurrent endometrial cancer were analyzed. Secondary cytoreductive surgery was performed in 56.2% of cases (186 patients). Complete gross resection was achieved in 178 patients (95.7%). Complete gross resection conferred a statistically significant survival benefit both for post-relapse survival and post-relapse free survival (3 years post-relapse survival: 75.4% vs 56.4%, p<0.001; 3 years post-relapse free survival: 32.6% vs 26.5%, p=0.027). At multivariate Cox regression analysis, age ≥75 years, Eastern Cooperative Oncology Group Performance Status ≥2, the advanced-metastatic risk group, complete gross resection, and multiple site relapses were identified as independent significant predictors for post-relapse survival; regarding post-relapse free survival, only age ≥75, the high and advanced-metastatic risk groups, and complete gross resection confirmed their statistical significance. Secondary cytoreductive surgery with achievement of complete gross resection was confirmed to be an independent positive predictor for survival in patients with recurrent endometrial cancer and should be considered a valid primary treatment in the therapeutic decision-making process.

Hysteroscopic endometrial tumor localization and sentinel lymph node mapping. An upgrade of the hysteroscopic role in endometrial cancer patients

Given the growing interest in sentinel node mapping (SLN) biopsy in Endometrial Cancer (EC) patients, many efforts have been made to maximize the SLN bilateral detection rate. However, at present, no previous research assessed the potential correlation between primary EC location in the uterine cavity and SLN mapping. In this context, this study aims to investigate the possible role of intrauterine EC hysteroscopic localization in predicting SLN nodal placement. EC patients surgically treated from January 2017 to December 2021 were retrospectively analyzed. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and SLN mapping. During hysteroscopy, the location of the neoplastic lesion was described as follows: uterine fundus (comprising the most cranial portion of the uterine cavity up to the tubal ostium including the cornual areas), corpus uteri (from the tubal ostium to the inner uterine orifice), and diffuse (when the tumor invades more than 50% of the uterine cavity). Three hundred ninety patients met the inclusion criteria. The tumor pattern diffused to the whole uterine cavity was statistically associated with SLN uptake on common iliac lymph nodes (OR 2.4, 95%CI 1-5.8, p = 0.05). Patients'age is an independent factor associated with SLN failure (OR: 0.95, 95%CI 0.93-0.98, p < 0.001). The study showed a statistically significant association between EC hysteroscopically spread throughout the whole uterine cavity and SLN uptake at the common iliac lymph nodes. Furthermore, patient age negatively affected the SLN detection rate.

Long-term survival outcomes in high-risk endometrial cancer patients undergoing sentinel lymph node biopsy alone versus lymphadenectomy

Endometrial cancer is the most common gynecologic neoplasm. To date, international guidelines recommend sentinel lymph node biopsy for low-risk neoplasms, while systematic lymphadenectomy is still considered for high-risk cases. This study aimed to compare the long-term survival of high-risk patients who were submitted to sentinel lymph node biopsy alone versus systematic pelvic lymphadenectomy. Patients with high-risk endometrial cancer according to the 2021 European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology risk classification were retrospectively analyzed. The primary aim of the study was to compare the long-term overall survival and disease-free survival of high-risk endometrial cancer patients undergoing sentinel lymph node biopsy versus systematic lymphadenectomy. A supplementary post-hoc survival analysis of cases with nodal metastasis was performed to compare sentinel lymph node and lymphadenectomy survival outcomes in this subset of patients. The study enrolled 237 patients with histologically proven high-risk endometrial cancer. Patients were followed up for a median of 31 months (IQR 18-40). During the follow-up, 38 (16.0%) patients had a recurrence, and 19 (8.0%) patients died. Disease-free survival (85.2% vs 82.8%; p=0.74) and overall survival (91.3% vs 92.6%; p=0.62) were not different between the sentinel lymph node alone and lymphadenectomy groups. Furthermore, neither overall survival (96.1% vs 91.4%; p=0.43) nor disease-free survival (83.7% vs 76.4%; p=0.46) were different among sentinel lymph node alone and lymphadenectomy groups in patients with nodal metastasis. Sentinel lymph node mapping alone in high-risk endometrial cancer appears to be an oncologically safe technique over a long observational time. Systematic lymphadenectomy in this population does not offer a survival advantage.

A large multicenter propensity match study of sentinel lymph node biopsy feasibility in endometrioid variants of endometrial cancer

Sentinel lymph node (SLN) biopsy algorithm has been routinely applied in all endometrial endometrioid tumors, however, no studies analyzed the feasibility of SLN mapping in endometrioid variants (EV), which included villoglandular, secretory, ciliated cell, mucinous, and squamous differentiation. This study aimed to demonstrate the feasibility of SLN biopsy in EV of EC. All patients undergoing minimally invasive surgical treatment for early-stage EC were included in the study. Patients were divided into 2 study groups: Group 1 which included patients with EV, and Group 2 which included patients with typical endometrioid histology. A propensity match analysis was performed according to age (≥65 years vs. no), BMI (≥30 kg/m After a 1:5 propensity-matched analysis, a total of 458 patients were identified (Group 1 n = 77, Group 2 n = 381). Overall detection rate was not statistically significant between the EV and the typical endometrioid group (94.8% vs. 92.4%, p = 0.319). Furthermore, neither bilateral nor unilateral detection rate was different between the two groups (70.1% vs. 74.8%, p = 0.267, and 23.4% vs. 17.8%, p = 0.120). BMI ≥30 kg/m SLN research/detection for EV of endometrial cancer is a feasible and highly sensitive technique. Obesity was confirmed to be a risk factor for SLN failure.

Extra-cranial meningioma associated with relapse of immature ovarian teratoma

Minimally invasive adrenalectomy: a personalized surgical approach in recurrent cervical cancer

Role of minimally invasive secondary cytoreduction in patients with recurrent ovarian cancer

Retrospective series have shown minimally invasive secondary cytoreductive surgery is a feasible approach in selected cases of recurrent ovarian cancer. However, no predictors of minimally invasive secondary cytoreductive surgery feasibility are currently available. This study aims to identify predictive factors of minimally invasive secondary cytoreductive surgery feasibility and to compare perioperative and survival outcomes in a matched series of recurrent ovarian cancer patients who underwent secondary cytoreduction via an open or minimally invasive surgical approach. We retrospectively identified all platinum-sensitive recurrent epithelial ovarian cancer patients who underwent minimally invasive or laparotomic secondary cytoreductive surgery between January 2013 and July 2020. Each patient underwent a preoperative positron emission tomography (PET) computerized tomography (CT) scan and diagnostic laparoscopy before secondary cytoreductive surgery. A 1:2 propensity score-matched analysis was performed to balance predictive factors of minimally invasive secondary cytoreductive surgery. Overall, 276 patients were identified (62 minimally invasive and 214 open), and a complete gross resection was achieved in 262 (94.9%) patients. At multivariate analysis, predictive factors for minimally invasive secondary cytoreductive surgery were neoadjuvant chemotherapy at first diagnosis (p=0.007), site of recurrence (p=0.031), and number of lesions (p=0.001). In the 1:2 propensity-matched population (39 minimally invasive and 78 open), complete gross resection was similar for both groups (p=0.082). Early post-operative complications were significantly higher in the laparotomy (33.3%) than in the minimally invasive surgery (10.3%) group (p=0.004). Only one (2.6%) patient experienced a grade >3 early post-operative complication in the minimally invasive surgery group compared with 13 (16.7%) patients in the open cohort (p<0.001). The median follow-up period was 32 months (range: 1-92) in the propensity-matched population. The median post-recurrence survival was 81 months in the minimally invasive surgery group and was not reached in the open group (p=0.11). Patients with single or oligometastatic recurrences can be offered minimally invasive secondary cytoreductive surgery, mainly if localized in the lymph-nodes, and/or if they received neoadjuvant chemotherapy at primary diagnosis. Minimally invasive secondary cytoreductive surgery is associated with favorable perioperative outcomes with no differences in terms of post-recurrence survival with respect to open approach.

Ovarian cancer metastases in the liver area: proposal of a standardized anatomo-surgical classification

How should randomized controlled trials in epithelial ovarian cancer be interpreted?

Nomogram to predict feasibility of minimally invasive interval debulking surgery in advanced ovarian cancer

Currently, there is no clear guidance defining the ideal candidate for minimally invasive interval debulking surgery. This study aimed to identify predictive factors for a minimally invasive approach in patients with advanced ovarian cancer who are candidates for interval debulking surgery after neoadjuvant chemotherapy. This was a single institution retrospective study conducted between January 2014 and June 2020 Perioperative variables were used to predict the likelihood of minimally invasive interval debulking surgery using multivariable models. A nomogram was developed, and internal validation was performed using the bootstrapping correction technique. This nomogram was built to visualize the effect of perioperative variables on the estimated probability of minimally invasive interval debulking surgery in patients with a clinical response after neoadjuvant chemotherapy. We used the four significant perioperative variables according to logistic regression. A total of 108 (28.4%) and 272 (71.6%) patients underwent interval debulking surgery by a minimally invasive or open approach, respectively. Absence of omental cake (odds ratio (OR) 9.15, 95% confidence interval (CI) 4.26 to 19.64, p<0.001), high volume surgeon (OR 5.43, 95% CI 2.75 to 10.71, p<0.001), less than two peritoneal sites involved (OR 2.94, 95% CI 1.34 to 6.43, p=0.007), and CA125 normalization (OR 1.79, 95% CI 1.05 to 3.36, p=0.049) correlated with the feasibility of minimally invasive interval debulking surgery at multivariate analysis. The calibration plot demonstrated good agreement between the predicted and actual probability of minimally invasive interval debulking surgery (p=0.93, Hosmer-Lemeshow test). Our nomogram may serve as a useful tool to choose the surgical approach in patients with advanced ovarian cancer undergoing interval debulking surgery.

Robotic approach for the treatment of gynecological cancers recurrences: A ten-year single-institution experience.

Although the management of gynecological cancers recurrences may be challenging, due to the heterogeneity of recurrent disease, the aim of this work is to present a descriptive analysis of gynecological malignancies recurrences in our institution treated by robotic approach. We performed a retrospective review and analysis of data of patients who underwent robotic surgery for recurrent gynecological malignancies at Catholic University of the Sacred Hearth, Rome, from January 2013 to January 2024. A total of 54 patients underwent successful robotic cytoreductive surgery. The median age was 63 years; the median BMI was 33 kg/m Robotic approach in the treatment of recurrent gynecological cancers should be considered in selected patients with oligometastatic disease, in high-volume centers with expert surgeons, particularly in obese patients.

Natural language processing as consultation service platform or clinical decision support system in gynecologic oncology: a systematic review.

Natural language processing is emerging as a key application of artificial intelligence in oncology. This systematic review aims to evaluate the performance and methodological frameworks of natural language processing systems in gynecologic oncology. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. MEDLINE, EMBASE, and Web of Science were searched for studies published between January 2015 and February 2025. Outcomes were synthesized across 3 research questions: the accuracy of natural language processing systems used as consultation service platforms; the accuracy of natural language processing systems used as clinical decision support systems; and the benchmarking methodologies applied, including their associated methodological outcomes. Consultation service platforms deliver general medical information, whereas clinical decision support systems provide recommendations that are integrated into the patient's clinical workflow. This review analyzed 12 retrospective studies. Consultation service platforms were less accurate than clinicians (60% vs 86.7%) and rated lower in response quality (2.96/5 vs 4.2/5) but outperformed guideline-based answers (1.54/2 vs 1.38/2). In cervical cancer, ChatGPT surpassed experts (7.0 vs 6.1). ChatGPT-4 showed a concordance of 70% with the National Comprehensive Cancer Network and 60% with the European Society of Gynaecological Oncology guidelines in clinical decision support tasks, with an overall recommendation accuracy of 75%. IBM Watson achieved a 72.8% concordance with guidelines. Prompting was applied from 100% to 37.5% across studies. Qualitative benchmarking varied across studies: 83.3% used clinical guidelines and 37.5% of consultation service platforms studies used expert answers. Four- or 5-point scales and binary scoring were used to assess consultation service platforms and clinical decision support systems, respectively. Clinicians remain superior in complex reasoning, but natural language processing systems demonstrate robust performance in guideline-driven tasks, with advantages in speed, readability, and reproducibility. However, performance declined in nuanced scenarios and among under-represented patient sub-groups. Large language models currently play a supportive rather than substitutive role in gynecologic oncology.