Virginia Vargiu

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.

Sentinel-node biopsy in apparent early stage ovarian cancer: final results of a prospective multicentre study (SELLY)

To evaluate the sensitivity and specificity of sentinel-lymph-node mapping compared with the gold standard of systematic lymphadenectomy in detecting lymph node metastasis in apparent early stage ovarian cancer. Multicenter, prospective, phase II trial, conducted in seven centers from March 2018 to July 2022. Patients with presumed stage I-II epithelial ovarian cancer planned for surgical staging were eligible. Patients received injection of indocyanine green in the infundibulo-pelvic and, when feasible, utero-ovarian ligaments and sentinel lymph node biopsy followed by pelvic and para-aortic lymphadenectomy was performed. Histopathological examination of all nodes was performed including ultra-staging protocol for the sentinel lymph node. 174 patients were enrolled and 169 (97.1 %) received study interventions. 99 (58.6 %) patients had successful mapping of at least one sentinel lymph node and 15 (15.1 %) of them had positive nodes. Of these, 11 of 15 (73.3 %) had a correct identification of the disease in the sentinel lymph node; 7 of 11 (63.6 %) required ultra-staging protocol to detect nodal metastasis. Four (26.7 %) patients with node-positive disease had a negative sentinel-lymph-node (sensitivity 73.3 % and specificity 100.0 %). In a multicenter setting, identifying sentinel-lymph nodes in apparent early stage epithelial ovarian cancer did not reach the expected sensitivity: 1 of 4 patients might have metastatic lymphatic disease unrecognized by sentinel-lymph-node biopsy. Nevertheless, 35.0 % of node positive patients was identified only thanks to ultra-staging protocol on sentinel-lymph-nodes.

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.

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.

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.

Rectosigmoid Mesorectal-Sparing Resection in Advanced Ovarian Cancer Surgery

Ovarian cancer is the most lethal of all gynecologic cancers.

Hormone replacement therapy and cervical cancer: a systematic review of the literature

Gynecological tumor treatment, including cervical cancer (CC) treatment, often leads to iatrogenic premature menopause. This highlights the critical importance of investigating indications for hormone replacement therapy (HRT), as most patients, thanks to the improvement in diagnosis and treatment, have to deal with the sequelae of their cancer treatments for many years. This systematic review aims to provide an overview of the current knowledge regarding the risks of HRT and CC. In particular, we aim to investigate whether the use of HRT can increase CC incidence, and evaluate its risk in CC survivors. A systematic review, in agreement with PRISMA guidelines, of the English literature present in PubMed and SCOPUS has been performed. A total of 2805 articles have been screened, of which 10 were considered eligible. Several studies reported a significantly reduced risk of developing cervical squamous cell carcinoma in postmenopausal women treated with HRT, while a weak increase in the incidence of adenocarcinoma has been shown. No evidence reports a harmful effect of HRT on CC oncological outcome, while several benefits, in terms of reduced metabolic risk and increased quality of life, have been described, thus concluding that HRT should be offered to young CC survivors for the management of early menopause.

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.

Patent Blue SLN in Early Ovarian Cancer Prospective Study (FIGO I-II) Evaluating Patent Blue SLN Mapping. Injection Into IP/UO Ligaments in Situ. Goals: Assess Feasibility and Accuracy vs Standard Lymphadenectomy to Minimize Surgical Morbidity

the standard of care in case of early ovarian cancer (stage I or II) is a complete surgery. This surgery includes : hysterectomy (remove of the uterus), bilateral salpingo-oophorectomy (remove of the adnexa), omentectomy (remove of the epiploon), bilateral pelvic lymphadenectomy (remove of pelvic lymph nodes) and para-aortic lymphadenectomy (remove of para-aortic lymph nodes). This procedure is diagnostic, curative and prognostic surgery. In fact, it allows us provider care giver to stratify the stage of the cancer, hence we give the appropriate adjuvant therapy. However, this surgery, especially the extended lymphadenectomy, is associated with some risks: lymphocele, vessel injury, blood loss, morbidity, long recovery period ... In order to reduce these risks, we propose a sentinel lymph node biopsy. This intervention allows us to detect first lymph node relay whether pelvic or para-aortic. In our study, we chose the patent blue dye as a tracer. This tracer is widely used in oncologic surgery (for example in breast cancer) and approved but not in ovarian cancer yet. During surgery for early stage ovarian cancer, we will inject the patent blue dye on both side of the ovarian tumor. Then, we will check for first colorful lymph node, in both pelvic and para-aortic regions. We will send these dissected lymph node to pathology for analysis. Finally, we will continue the procedure as the standard of care. Our objective is to compare the results between the sentinel lymph node and the complete lymphadenectomy and to study the technique of sentinel lymph node biopsy using the blue patent dye as tracer.