Glauco Baiocchi

Uterine transposition for fertility and ovarian function preservation after radiotherapy

To evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation. This prospective multicenter observational study included patients with non-gynecologic pelvic cancers who underwent pelvic radiation as part of their cancer treatment between June 2017 and June 2019. For inclusion in the study, patients were required to have normal menstrual cycles and hormone levels (follicle-stimulating hormone, luteinizing hormone, and estrogen) before treatment. Uterine transposition to the upper abdomen was performed prior to irradiation. Clinical examinations and Doppler ultrasonography were used to evaluate the gonadal vasculature post-surgery. The uterus was repositioned into the pelvis 2-4 weeks after radiation therapy or at the time of rectosigmoid resection in patients with rectal cancer who had undergone neoadjuvant treatment. Cancer treatment and follow-up were performed according to standard guidelines. Eight patients (seven with rectal cancer and one with pelvic liposarcoma) underwent uterine transposition at a median age of 30.5 years (range 19-37). The uterus was successfully preserved in six patients, accompanied by normal menses, hormonal levels, and vaginal intercourse after treatment. One patient with rectal cancer died of carcinomatosis 4 months after uterine transposition. One patient presented with uterine necrosis 4 days after uterine transposition, and the uterus was removed; however, one ovary was preserved. Cervical ischemia was the most common post-surgical complication in three (37.5%) patients. Three patients attempted to conceive, and two (66%) were spontaneously successful and delivered healthy babies at 36 and 38 weeks by cesarean section without complications. Uterine transposition is a feasible procedure for preserving gonadal and uterine function in patients requiring pelvic radiotherapy for non-gynecological cancer, with the potential for achieving spontaneous pregnancy and successful delivery.

Empty node packet in endometrial cancer: predictors and clinical significance in the sentinel lymph node era

This study aimed to evaluate clinical and pathological factors associated with the occurrence of empty node packets during sentinel lymph node mapping in patients with endometrial cancer. We performed a retrospective cohort study including patients with histologically confirmed endometrial carcinoma who underwent sentinel lymph node mapping between November 2012 and December 2023. An empty node packet was defined as the intra-operative removal of a presumed sentinel node with no lymphoid tissue identified on final pathological examination. Logistic regression models were used to identify independent predictors. Of 489 patients who had sentinel lymph node mapped, 23 (4.7%) had an empty node packet. In the univariate analysis, body mass index and myometrial invasion were significantly associated (p < .05). In the multi-variable analysis, only body mass index remained independently associated (odds ratio 1.075, 95% confidence interval 1.01 to 1.14, p = .022) with an empty node packet. Tumor histology, grade, type of tracer, and surgical approach were not associated. No nodal recurrences occurred in patients with an empty node packet. Empty node packets are uncommon but clinically relevant during sentinel lymph node mapping for endometrial cancer. Higher body mass index was the only independent predictor, underscoring the influence of patient-related factors on mapping accuracy.

Endometrial carcinosarcoma without myoinvasion

Uterine carcinosarcoma without myoinvasion, limited to the endometrial lining/polyp or with no residual uterine disease at the time of hysterectomy, is extremely uncommon, with unknown oncologic outcomes. Thus, this study aimed to evaluate the long-term outcomes of patients with carcinosarcoma without myoinvasion. Patients with International Federation of Gynecology and Obstetrics 2009 stage IA carcinosarcoma without myoinvasion who underwent surgery from December 1998 to January 2023 were identified from 11 centers worldwide. Patients were classified by tumor status (limited to the endometrium, limited to polyp, no residual disease in the hysterectomy specimen) and by type of adjuvant therapy (chemotherapy vs no chemotherapy). Survival analysis follow-up was limited to the first 5 years after surgery. Of 97 patients included, 28 (28.9%) had disease confined to a polyp, 55 (56.7%) to the endometrium, and 14 (14.4%) had no residual disease in the hysterectomy specimen. Patients received observation only (n=16, 16.5%), vaginal brachytherapy alone (n=14, 14.4%), external beam radiation therapy ± vaginal brachytherapy (n=5, 5.2%), chemotherapy ± vaginal brachytherapy (n=51, 52.6%), and chemotherapy and external beam radiation therapy ± vaginal brachytherapy (n=7, 7.2%), whereas adjuvant therapy was unknown in 4 patients (4.1%). A total of 29 patients (29.9%) recurred, mostly with a distant pattern of relapse. The 5-year recurrence-free survival was 63.5% (95% CI 53.4% to 75.4%) and the overall survival was 72.0% (95% CI 62.6% to 82.9%). The median follow-up for patients without recurrence was 56.9 months (interquartile range; 21.8-72.9). No significant differences were observed in recurrence-free survival and overall survival based on status of the tumor (p=.99 and p=.43, respectively). The difference in recurrence-free survival and overall survival was not statistically significant based on the receipt of chemotherapy (p=.08 and p=.07, respectively). Patients with carcinosarcoma without myoinvasion have a poor prognosis, with a high recurrence rate with distant pattern. The use of chemotherapy did not achieve statistical significance but may be limited by our small series.

Subclonal loss of DNA mismatch repair proteins in endometrial carcinomas: an unusual pattern with distinct molecular characteristics

Subclonal loss of mismatch repair (MMR) proteins in endometrial carcinoma has recently been identified through immunohistochemistry (IHC) evaluations, characterized by discrete areas of tumors with complete loss of nuclear expression adjacent to tumor cells with retaining expression. Controversies persist regarding reporting findings and managing such cases. Therefore, we conducted a detailed clinicopathological and molecular analysis on a large cohort of endometrial carcinoma cases with subclonal loss of MMR proteins to explore potential reclassification into different molecular categories that could influence diagnostic and treatment strategies. Eligible endometrial carcinoma cases underwent IHC evaluation for PMS2/MLH1/MSH2/MSH6. Cases showing subclonal loss of MMR proteins underwent macrodissection of both proficient and deficient MMR expression areas, followed by testing for microsatellite instability (Idylla), MLH1 promoter methylation (next-generation sequencing), POLE mutations (next-generation sequencing), and p53 expression (IHC). The proposed molecular evaluation was performed in both proficient and deficient areas. Clinical and pathological data for patients with subclonal loss were also analyzed. We evaluated 356 cases of endometrial carcinoma, identifying subclonal loss in 16 patients (4.4%), predominantly endometrioid (15 cases, 93.75%) and International Federation of Gynecology and Obstetrics stage I (13 cases, 81.25%). Subclonal loss of MSH6 occurred independently in 6 cases (37.5%), and concurrently with subclonal loss of MLH1 in 2 cases (12.5%). Complete loss of MLH1/PMS2 was observed in 2 cases (12.5%). MLH1 promoter methylation was detected in 6 cases (37.5%), with 4 cases showing methylation in both areas analyzed. POLE mutations were found in 3 cases (18.75%), occurring in both deficient and proficient areas. The correlation between IHC findings and molecular results varied, providing valuable predictive and prognostic insights that could guide treatment decisions in some patients. Molecular evaluation should be standard practice in all endometrial carcinoma cases exhibiting subclonal loss of MMR proteins to accurately delineate tumor characteristics. Subclonal loss should be reported distinctly, warranting a more comprehensive diagnostic approach to enhance tumor classification.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

To evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer. A prospective cohort included women with early-stage endometrial carcinoma who underwent lymph node staging, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND group (sentinel lymph node biopsy with addition of systematic lymphadenectomy). The patients had at least 12 months of follow-up, and QoL was assessed by European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30) and EORTC-QLQ-Cx24. Lymphedema was also assessed by clinical evaluation and perimetry. 152 patients were included: 113 (74.3%) in the SLN group and 39 (25.7%) in the SLN+LND group. Intra-operative surgical complications occurred in 2 (1.3%) cases, and all belonged to SLN+LND group. Patients undergoing SLN+LND had higher overall complication rates than those undergoing SLN alone (33.3% vs 14.2%; p=0.011), even after adjusting for confound factors (OR=3.45, 95% CI 1.40 to 8.47; p=0.007). The SLN+LND group had longer surgical time (p=0.001) and need for admission to the intensive care unit (p=0.001). Moreover, the incidence of lymphocele was found in eight cases in the SLN+LND group (0 vs 20.5%; p<0.001). There were no differences in lymphedema rate after clinical evaluation and perimetry. However, the lymphedema score was highest when lymphedema was reported by clinical examination at 6 months (30.1 vs 7.8; p<0.001) and at 12 months (36.3 vs 6.0; p<0.001). Regarding the overall assessment of QoL, there was no difference between groups at 12 months of follow-up. There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found in overall QoL between SLN and SLN+LND groups.

Residual Disease after Operative Hysteroscopy in Patients with Endometrioid Endometrial Cancer Associated with Polyps

Abstract Objective To evaluate the presence of residual disease in the uterine specimen after hysteroscopic polypectomy or polyp biopsy in patients with endometrioid endometrial cancer (EC). Methods We analyzed a series of 104 patients (92 cases from the Hospital AC Camargo and 12 from the Hospital do Servidor Público Estadual de São Paulo) with polyps that were diagnosed by hysteroscopy, showing endometrioid EC associated with the polyp or in the final pathological specimen. Patients underwent a surgical approach for endometrial cancer from January 2002 to January 2017. Their clinical and pathological data were retrospectively retrieved from the medical records. Results In 78 cases (75%), the polyp had EC, and in 40 (38.5%), it was restricted to the polyp, without endometrial involvement. The pathologic stage was IA in 96 cases (92.3%) and 90 (86.5%) had histologic grade 1 or 2. In 18 cases (17.3%), there was no residual disease in the final uterine specimen, but only in 9 of them the hysteroscopy suggested that the tumor was restricted to the polyp. In 5 cases (4.8%) from the group without disease outside of the polyp during hysteroscopy, myometrial invasion was noted in the final uterine specimen. This finding suggests the possibility of disease extrapolation through the base of the polyp. Conclusion Patients with endometrioid EC associated with polyps may have the tumor completely removed during hysteroscopy, but the variables shown in the present study could not safely predict which patient would have no residual disease.

Impact of molecular classification on recurrence risk in endometrial cancer patients with lymph node metastasis: multicenter retrospective study

To assess the distribution of molecular classes and their impact on the risk of recurrence in endometrial cancer patients with lymph node metastasis at the time of primary surgery. Endometrial cancer patients with lymph node micrometastasis or macrometastasis (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIC) after surgical staging at five referral centers worldwide from October 2013 to September 2022 who underwent molecular classification were identified. Endometrial cancers were categorized into four molecular classes: POLE mutated, mismatch repair deficient, p53 abnormal, and no specific molecular profile. Survival analyses using Kaplan-Meier and Cox models (univariate and multivariate) were conducted to evaluate the relationship between molecular class and 5-year recurrence free survival. 131 patients were included: 55 (42.0%) no specific molecular profile, 46 (35.1%) mismatch repair deficient, 1 (0.8%) POLE mutated, and 29 (22.1%) p53 abnormal. During a 5 year follow-up period, 50 (38.2%) patients experienced a recurrence with a median time of 1.2 years (interquartile range (IQR) 0.5-1.8). Median follow-up for the remaining 81 patients was 3.1 years (IQR 1.3-4.5). Survival analysis revealed a significant difference in recurrence-free survival between no specific molecular profile, mismatch repair deficient, and p53 abnormal classes (log rank p<0.01). In a model adjusted for type of lymph node metastasis and tumor grade, the molecular class did not retain significance (p=0.13), while in a model adjusted for type of lymph node metastasis and adjuvant therapy, the molecular class retained significance (p<0.01). Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.

Sentinel node mapping decreases the risk of failed detection of isolated positive para-aortic lymph node in endometrial cancer

Isolated positive para-aortic lymph node metastasis in endometrial cancer is an uncommon event, ranging from 1% to 3%. Our aim was to evaluate the impact of sentinel lymph node (SLN) mapping on the risk of isolated positive para-aortic lymph node metastasis. We retrospectively evaluated a series of 426 patients who underwent SLN mapping with at least one SLN detected from January 2013 to December 2021 (SLN group) compared with a historical series of 209 cases who underwent a systematic pelvic and para-aortic lymphadenectomy between June 2007 and April 2015 (LND group). Isolated para-aortic lymph node metastasis recurrences were included in the SLN group analysis. In the SLN group, 168 cases (39.4%) had backup systematic lymphadenectomy, and 56 (13.1%) had positive lymph nodes compared with 34 (16.3%) in LND group (p=0.18). The SLN group had higher rates of minimally invasive surgeries (p<0.001) and presence of lymphovascular space invasion (p<0.001). Moreover, SLN group had fewer other uterine risk factors, such as high-grade tumors (p<0.001), and deep myometrial invasion (p<0.001). We found that SLN mapped outside the pelvis at pre-sacral, common iliac areas, and para-aortic regions in 2.8% (n=12), 11.5% (n=49), and 1.6% (n=7) of cases, respectively. Overall, 52 (12.2%) patients had positive SLNs, and 3 (5.7%) positive SLNs were found outside the pelvis-one in the pre-sacral region, one in the common iliac area, and one in the para-aortic region. An isolated para-aortic lymph node was found in only 2 (0.5%) cases in the SLN group compared with 7 (3.3%) cases in the LND group (p=0.004). SLN protocol accurately predicts lymph node status and may decrease the risk of failed identification of isolated para-aortic lymph node metastasis compared with systematic lymphadenectomy.

ASO Author Reflections: Sentinel Lymph Node Biopsy in Endometrial Cancer: Beyond Oncologic Outcomes

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial)

Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking. The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy. This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy. Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy. The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer. 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. NCT03366051.

Impact of Sentinel Node Mapping in Decreasing the Risk of Lymphocele in Endometrial Cancer

Due to the growing evidence of sentinel lymph node (SLN) mapping in endometrial cancer (EC), our aim was to evaluate the impact of SLN mapping and other clinical-pathological variables in the risk of developing lymphocele. We retrospectively analyzed a series of patients with ECs who underwent lymph node staging with SLN mapping with or without systematic pelvic ± para-aortic lymphadenectomy from November 2012 to January 2020. The lymphocele diagnosis was performed by computed tomography or magnetic resonance imaging. Of 348 patients included, 178 underwent SLN mapping only and 170 underwent SLN mapping and systematic lymphadenectomy (46.5% pelvic only; 53.5% pelvic and para-aortic). Seventy-three (21%) patients had open surgery and 275 (79%) had a minimally invasive approach. After a median follow-up of 25.4 months, the overall prevalence of lymphocele was 8.6% (n = 30), with 29 cases in a pelvic location. Lymphocele was found in 3.4% (n = 6/178) of patients submitted to SLN mapping only, compared with 14.1% (n = 24/170) among those who underwent SLN with lymphadenectomy (p = 0.009). Among those patients with lymphocele, seven (23.3%) were symptomatic and five (16.6%) required drainage. All symptomatic cases occurred in lymphoceles larger than 4 cm (p = 0.001). Neither resected lymph node count nor the type of systematic lymphadenectomy were related to the presence of lymphocele. Systematic lymphadenectomy was the only factor that emerged as a risk factor for the presence of lymphocele in multivariate analysis (odds ratio 3.68, 95% confidence interval 1.39-9.79; p = 0.009). Our data suggest that SLN mapping independently decreases the risk of lymphocele formation compared with full lymphadenectomy in EC.

Outcomes and toxicity after salvage radiotherapy for vaginal relapse of endometrial cancer

Studies of salvage radiotherapy in locally recurrent endometrial cancer remain limited. The aim of this study was to evaluate the efficacy of salvage radiotherapy for vaginal relapse of endometrial cancer and to explore prognostic factors associated with outcomes. We evaluated 30 patients treated with salvage external-beam radiotherapy and/or vaginal brachytherapy for vaginal relapses of endometrial cancer between 2009 and 2018. The inclusion criteria were: pathologically-confirmed recurrence; loco-regional relapse (in absence of distant metastases); and salvage treatment including external-beam radiotherapy and/or vaginal brachytherapy. Outcomes were evaluated via Kaplan-Meier, with the log-rank test employed to compare differences among various groups and identify prognostic factors. 30 patients developed vaginal recurrence at a median time of 20.6 months (range 2-219) post-hysterectomy. The most common site of recurrence was the vaginal apex (60%), followed by the distal vagina (10%). Salvage radiotherapy entailed combination external-beam radiotherapy and vaginal brachytherapy (n=24) or single modality treatment (n=6), along with concurrent chemotherapy in 20 cases. At a median follow-up of 4.4 years (range 0.1-130) post-radiotherapy, the 5 year rates of local control, regional control, metastasis-free interval, disease-free interval, and overall survival were 89%, 91.5%, 75.5%, 69%, and 83%, respectively. Factors associated with improved disease-free interval included: endometrioid histology (p=0.03), isolated vaginal relapse (p=0.003), late recurrence (>9 months) (p=0.007), and combined modality radiotherapy (p=0.001). The only factor associated with overall survival was isolated vaginal relapse (in the absence of other recurrent disease) (p=0.02). Regarding toxicity, 18% of patients experienced acute grade ≥3 events (most commonly gastrointestinal). The 5 year rates of rectal bleeding, small bowel obstruction, and pelvic fracture were 31%, 18%, and 13%, respectively. Salvage radiotherapy imparts excellent loco-regional control for vaginal relapses of endometrial cancer and should entail combination external-beam radiotherapy and vaginal brachytherapy. Patients should be closely monitored for late gastrointestinal toxicity following salvage radiotherapy.

ASO Author Reflections: Could Ovarian Preservation be Considered for Young Women with Endometrial Cancer?

Adnexal Involvement in Endometrial Cancer: Prognostic Factors and Implications for Ovarian Preservation

To determine the risk factors related to adnexal involvement in endometrial cancer (EC) and its implications for ovarian preservation in young women. We analyzed a series of 802 patients who were treated at AC Camargo Cancer Center from July 1991 to July 2017. Patients who had peritoneal or systemic dissemination (stage IV) were excluded. Chi square and Fisher's exact tests were used to analyze the correlations between categories and clinicopathological variables. Multivariate analysis was performed by logistic regression. Forty-nine (6.2%) patients had adnexal involvement-43 (5.4%) ovarian and 24 (2.9%) tubal. After excluding the 14 (28%) cases with suspicious findings, 788 subjects were analyzed and adnexal involvement found in 35 (4.4%) cases. Adnexal involvement was statistically related to non-endometrioid histologies (12.6% vs. 3.1%; p < 0.001), lymph node metastasis (17% vs. 2.6%; p < 0.001), histological grade 3 tumors (9.4% vs. 2.1%; p < 0.001), presence of LVSI (14.2% vs. 2.4%; p < 0.001), and deep myometrial invasion (≥ 50%) (10.8% vs. 3.5%; p < 0.001). Although age younger than 45 years had higher risk of adnexal involvement, it was not statistically significant (8.9% vs. 4.2%; p = 0.13). Seven (14.2%) patients with adnexal involvement were aged < 45 years, 3 of whom (42.8%) had suspicious adnexal masses that were detected before surgery. Notably, all patients aged < 45 years and with adnexal involvement had at least 1 risk factor, such as presence of LVSI, grade 3 disease, node metastasis, or deep myometrial invasion. No patient with clinically normal ovaries and aged under 45 years, with endometrioid grades 1 and 2, superficial myometrial invasion, or node negativity had adnexal involvement. Ovarian preservation may be considered for patients younger than 45 years old with low-risk EC (grades 1 and 2 tumors, absence of LVSI, and myometrial invasion < 50%).

Brazilian Society of Surgical Oncology guidelines for surgical treatment of endometrial cancer in regions with limited resources

AbstractBackgroundApproximately 70% of cancer‐related deaths occur in low‐ and middle‐income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines.ObjectivesThe Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers.MethodsThe guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations.ResultsFor all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives.ConclusionsIt is possible to provide adequate treatment for most EC patients in resource‐limited areas, but the first option should be referral to specialized centers with more resources.

Size of Sentinel Node Metastasis Predicts Non-sentinel Node Involvement in Endometrial Cancer

To analyze the relationship between the size of metastatic sentinel lymph nodes (SLNs) and the risk of non-sentinel lymph node (non-SLN) metastasis in endometrial cancer. From a total of 328 patients with endometrial cancer who underwent SLN mapping from January 2013 to April 2019, 142 patients also underwent systematic completion pelvic ± paraaortic node dissections, and they form the basis of this study. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin-eosin stain was negative. The median age was 60 years. The overall detection rate for SLNs was 87.5%, and bilateral SLNs were observed in 66.2%, with a median of 2 SLNs resected (range 1-8). Twenty-nine (20.4%) cases had positive SLNs, with a median of one positive SLN. Regarding the size of SLN metastasis, 5 (3.5%) cases had isolated tumor cells (ITCs), 13 (9.2%) had micrometastases, and 11 (7.7%) had macrometastases. Notably, 14/29 (48.3%) had node metastases that were detected after IHC. Eight (27.6%) patients had positive non-SLNs, with a median count of 7 positive nodes (range 2-23). Regarding the size of SLN metastasis, non-SLN involvement was not present in cases with ITC (0/5) but was present in 15.4% (2/13) of cases with micrometastases and 54.5% (6/11) of cases with macrometastases. The only risk factor for positive non-SLNs was the size of SLN metastasis. Our data suggest that size of SLN metastasis is associated with the risk of non-SLN metastasis. No patients with ITCs in SLNs had another metastatic lymph node in this study.

The value of PET/CT for cytoreductive surgery selection in recurrent ovarian carcinoma

To evaluate the value of positron emission tomography/computed tomography (PET/CT) in predicting no residual disease (NRD) after secondary cytoreductive surgery (SCS) compared with MSK criteria, the iMODEL, and the AGO score. We analyzed 112 patients with platinum-sensitive ovarian carcinoma who underwent SCS. We excluded patients for whom PET/CT was not performed, those without sufficient data, and who received chemotherapy before SCS. Ultimately, 69 patients were included. Variables that correlated with NRD were peritoneal carcinomatosis index (odds ratio [OR]=0.91; 95% confidence interval [CI]=0.83-0.99; p=0.044), European Cooperative Oncology Group Performance Status (ECOG) 0 (OR=8.0; 95% CI=1.34-47.5; p=0.022), and ≤2 lesions by PET/CT (OR=4.36; 95% CI=1.07-17.7; p=0.039). Of the patients with ≤2 lesions by PET/CT, 48 (92.3%) underwent complete SCS. The sensitivity, positive predictive value, negative predictive value, and accuracy of PET/CT for NRD were 85.7%, 92.3%, 33.3%, and 81.2%, respectively. NRD was achieved after fulfilling the MSK criteria, iMODEL and AGO Score in 89.1%, 88.1% and 85.9%, respectively. The accuracy of the MSK criteria, iMODEL, and AGO score in predicting NRD was 87%, 83.3%, and 77.3%, respectively. The PET/CT findings agreed well with the AGO score and iMODEL. The addition of PET/CT to these models increased the NRD rates (92.2%, 91.8%, and 89.4% for MSK+PET/CT, iMODEL+PET/CT, and AGO+PET/CT, respectively), but lowered their accuracy. We observed NRD in 92.3% of patients with ≤2 lesions by PET/CT, with an accuracy of 81.2%. PET/CT did not increase the accuracy of the MSK criteria, iMODEL, or AGO score models.

Open Versus Minimally Invasive Radical Hysterectomy in Cervical Cancer: The CIRCOL Group Study

To analyze the survival outcomes of patients in a Brazilian cohort who underwent minimally invasive surgery (MIS) compared with open surgery for early stage cervical cancer. A multicenter database was constructed, registering 1280 cervical cancer patients who had undergone radical hysterectomy from 2000 to 2019. For the final analysis, we included cases with a tumor ≤ 4 cm (stages Ia2 to Ib2, FIGO 2018) that underwent surgery from January 2007 to December 2017. Propensity score matching was also performed. A total of 776 cases were ultimately analyzed, 526 of which were included in the propensity score matching analysis (open, n = 263; MIS, n = 263). There were 52 recurrences (9.9%), 28 (10.6%) with MIS and 24 (9.1%) with open surgery (p = 0.55); and 34 deaths were recorded, 13 (4.9%) and 21 (8.0%), respectively (p = 0.15). We noted a 3-year disease-free survival (DFS) rate of 88.2% and 90.3% for those who received MIS and open surgery, respectively (HR 1.32; 95% CI: 0.76-2.29; p = 0.31) and a 5-year overall survival (OS) rate of 91.8% and 91.1%, respectively (HR 0.80; 95% CI: 0.40-1.61; p = 0.53). There was no difference in 3-year DFS rates between open surgery and MIS for tumors ≤ 2 cm (95.7% vs. 90.8%; p = 0.16) or > 2 cm (83.9% vs. 85.4%; p = 0.77). Also, the 5-year OS between open surgery and MIS did not differ for tumors ≤ 2 cm (93.1% vs. 93.6%; p = 0.82) or > 2 cm (88.9% vs. 89.8%; p = 0.35). Survival outcomes were similar between minimally invasive and open radical hysterectomy in this large retrospective multicenter cohort.

Ovarian sparing cystectomy for borderline serous tumor through vNOTES (vaginal Natural Orifices Transluminal Endoscopic Surgery)

Impact of lymph node staging in presumed early-stage ovarian carcinoma

Our objective was to analyze the prevalence of lymph node metastasis in early-stage ovarian carcinoma after systematic lymph node dissection and its impact on indication of adjuvant chemotherapy. We evaluated a series of 765 patients diagnosed with ovarian carcinoma who underwent surgical treatment from February 2007 to December 2019. Patients with peritoneal disease and incomplete surgical staging were excluded. All cases underwent systematic pelvic and para-aortic lymphadenectomy up to the renal vessels. A total of 142 cases were analyzed. Median pelvic and para-aortic lymph node dissected were 30 (range, 6-81) and 21 (range, 3-86), respectively. Twelve (8.4%) patients had metastatic lymph nodes - high-grade serous, 10.4% (5/48); clear cell, 17.2% (5/29) and endometrioid, 5.7% (2/35). Any other histology (low grade serous, mucinous, carcinosarcoma or mixed) had lymph node metastasis. Notably, 50% of patients with positive lymph nodes had preoperative suspicious lymph nodes in imaging. The median hospital stay length was 6 days (range, 2-33) and 4.2% cases had grade ≥ 3 complications. A total of 110 (77.6%) patients underwent adjuvant chemotherapy and all cases had indication of adjuvant chemotherapy after histological type, despite the lymph node status. After a median follow-up of 52.5 months, we noted 24 (16.9%) recurrences. The 5-year recurrence-free survival and overall survival were 86.4% and 98.1%, respectively. High grade histology was the only variable that negatively impacted disease-free survival in univariate analysis [HR 4.70 (95%CI: 1.09-20); p = 0.037]. We found a positive lymph node rate of less than 10% after lymphadenectomy in presumed early-stage ovarian carcinoma. Lymph node status was not determinant for adjuvant chemotherapy.

Case Report of Small Cell Carcinoma of the Ovary, Hypercalcemic Type (Ovarian Rhabdoid Tumor) with SMARCB1 Mutation: A Literature Review of a Rare and Aggressive Condition

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive condition that is associated with the SMARCA4 mutation and has a dismal prognosis. It is generally diagnosed in young women. Here, we report a case of a young woman with SCCOHT harboring a rare molecular finding with a highly aggressive biological behavior. The patient had a somatic SMARCB1 mutation instead of an expected SMARCA4 alteration. Even though the patient was treated with high-dose chemotherapy followed by stem cell transplantation, she evolved with disease progression and died 11 months after her first symptoms appeared. We present a literature review of this rare disease and discuss the findings in the present patient in comparison to expected molecular alterations and options for SCCOHT treatment.

Comprehensive management of vulvovaginal cancers

AbstractVulvar and vaginal cancers represent rare malignancies, with an incidence of 2.7 per 100,000 women for vulvar cancer, predominantly affecting women older than 60 years, although rising rates are observed in younger demographics. Approximately 90% of vulvar cancers are squamous cell carcinoma and frequently are associated with human papillomavirus (HPV) infection. Vaginal cancer, constituting less than 1% of all female cancers, similarly exhibit HPV‐related trends. This review delineates the etiology, histopathology, and treatment strategies for carcinomas and vulvovaginal melanomas and sarcomas. Surgical intervention remains the primary treatment modality for vulvar cancer, involving tumor resection and inguinofemoral lymph node staging. For locally advanced vulvar carcinoma, chemoradiation is advised when exenterative surgery would be indicated. Recurrence rates within 2 years after diagnosis range from 12% to 37%. Unfortunately, systemic treatments for recurrent or metastatic disease are limited, with 5‐year survival rates at approximately 20%. Current evidence primarily derives from retrospective studies or small phase 2 trials or otherwise is extrapolated from the treatment of cervical cancer. Enrollment in clinical trials is strongly advocated, along with prompt access to best supportive care to mitigate the effect of locoregional progression on quality of life. Moreover, the psychosocial implications of treatment on body image and sexuality necessitate careful consideration. Future HPV vaccination initiatives may reduce cancer incidence, although significant effects of such vaccination will manifest over decades, underscoring the urgent need to enhance treatment efficacy and minimize morbidity in vulvar and vaginal cancers.

Vaginectomy with trachelectomy followed by ileal neovagina reconstruction and uterine corpus sparing for vaginal melanoma

Uterine transposition for gynecological cancers

Uterine transposition has emerged as an alternative for fertility preservation in women with pelvic malignancies that require radiotherapy. The goal of this study was to evaluate the short-term outcomes of patients undergoing uterine transposition after trachelectomy for cervical cancer or before chemoradiation for vaginal cancer. We retrospectively evaluated patients with early stage cervical cancer after radical trachelectomy or with vaginal cancer with indication for pelvic radiation who had uterine transposition performed as fertility sparing strategy. Four patients with cervical cancer and one patient with vaginal cancer were included. Median age was 32 years (range 28-38). All patients had squamous cell carcinomas. All patients with cervical cancer had radical trachelectomies with sentinel lymph node dissection (SLN). Two of these patients also had pelvic lymphadenectomies. Indications for adjuvant radiotherapy was due to Sedlis criteria in two patients and to lymph node metastasis in the other two patients. The patient with stage IIB vaginal cancer was recommended primary chemoradiation. All patients underwent uterine transposition before radiotherapy. The median uterine transposition surgical time was 90 min (range 80-205) and no early complications (30 days) occurred. Average time from uterine transposition to start of radiotherapy was 16 days (10-28). After radiation, the uterus along with the ovaries and tubes were repositioned and the residual cervix sutured to the vagina. One patient declined uterine reimplantation after radiation and underwent a hysterectomy. After a median follow-up of 25 months (range 1-30), all patients were without evidence of disease. All patients with preserved uterus have normal menses after treatment. One patient has attempted to conceive with IVF techniques without success. Uterine transposition may be an option in selected patients with cervical and vaginal cancers who want to preserve fertility. However, further studies that address its oncological safety and obstetrical outcomes are encouraged.

Immunohistochemical expression of ErbB/HER family proteins in patients with vulvar cancer

AbstractObjectiveTo investigate the immunohistochemical (IHC) expression of the ErbB/HER family in primary vulvar squamous cell carcinoma (VSCC).MethodsWe analyzed a series of 125 patients who were surgically treated for VSCC from January 1980 to June 2016. All cases had lymph node (LN) staging and 80 had LN metastasis. A tissue microarray was built for epidermal growth factor receptor (EGFR), HER2, HER3, and HER4 IHC staining.ResultsIn the primary tumor we found positive expressions for EGFR, HER2, HER3, and HER4 in 5%, 0.9%, 0.9%, and 22.8%, respectively. For the LN metastasis, expressions of EGFR and HER4 were positive in 22.2% and 39.1%, respectively. No cases had positive staining for HER2 and HER3 in the LN metastasis. For HER4, positive expression correlated with smaller tumor sizes (P = 0.02). However, positive HER4 was related to adverse prognostic factors such as: histological grade (P = 0.012), presence of lymphovascular space invasion (40.9% vs 16.2%; P = 0.035), and perineural invasion (57.1% vs 16.7%; P = 0.006). Notably, all cases with LN metastasis had positive HER4 in the primary tumor (P &lt; 0.001). ErbB/HER family expression was not related to worse survival.ConclusionEGFR, HER2, and HER3 were infrequently expressed in VSCC by IHC. HER4 IHC expression was found in 22.8% of cases and was related to adverse prognostic factors.

ASO Author Reflections: Minimally Invasive Radical Hysterectomy in Cervical Cancer: A Brazilian Multicentric Cohort Study (CIRCOL)

ASO Author Reflections: Is Residual Disease Predictable After Conization in Cervical Cancer?

Predictive Factors for Residual Disease After Conization in Cervical Cancer

The aim of this study was to evaluate predictive factors for the presence of residual disease after conization followed by definitive surgery in cervical cancer, and suggest a margin distance threshold that could predict residual disease. We retrospectively analyzed a series of 42 patients with early-stage cervical cancer who underwent primary conization before definitive surgical treatment from March 2009 to May 2020. All conization specimens were reviewed for endocervical, ectocervical, and radial margins. Cases with residual disease in magnetic resonance imaging before definitive surgery were excluded. Thirty-three (78.6%) patients underwent hysterectomies and 9 (21.4%) trachelectomies ± lymph node staging. Twelve (28.6%) cases were stage IA1, 5 (11.8%) cases were stage IA2, 13 (31%) cases were stage IB1, 11 (26.2%) cases were stage IB2, and 1 (2.4%) case was stage IIIC1 [International Federation of Gynecology and Obstetrics (FIGO) 2019]. We found residual disease in 17 (40.4%) surgical specimens. Of the 20 patients with negative margins, there were still 3 (15%) cases with residual disease. Conversely, residual disease was identified in 14 (63.6%) of the 22 patients with positive cone margins (p = 0.001). Tumor size [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.02-1.33] and positive endocervical margin status (OR 33.6, 95% CI 3.85-293.3) were related to a higher risk of residual disease in multivariate analysis. Notably, all patients with tumors larger than 2 cm had residual disease, in contrast to 29.4% in lesions up to 2 cm (p = 0.002). We found that tumor size and positive margin were predictive factors for residual disease. We could not suggest a reliable minimum margin distance threshold that could predict residual disease.

Pathological factors associated with non‐sentinel lymph node metastasis in early stage cervical cancer

AbstractObjectiveTo analyze the predictive factors for non‐sentinel lymph node (non‐SLN) metastasis in early‐stage cervical cancer.MethodsWe analyzed a series of 113 patients who underwent sentinel lymph node (SLN) mapping for cervical cancer. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin–eosin stain was negative.ResultsThe overall bilateral detection rate was 81.5%, with a median of two SLNs resected. The study ultimately included 92 patients with SLNs that were mapped who had also undergone systematic pelvic lymph node dissection. Thirteen (14.1%) patients had positive SLNs, with a median of one positive SLN. Regarding the size of SLN metastasis, one (1.1%) had isolated tumor cells (ITC), seven (7.6%) had micrometastases, and five (5.4%) had macrometastases. Notably, 46.1% (6/13) had lymph node metastases detected only after IHC. Five (38.5%) cases had positive non‐SLNs, with a median count of one positive lymph node. Parametrial invasion was the only risk factor for positive non‐SLN (p = .045). Regarding the size of SLN metastasis, non‐SLN involvement was present in the only case with ITC (1/1), 42.9% (3/7) of cases with micrometastases, and in 20% (1/5) with macrometastases.ConclusionsOur data suggest that parametrial invasion correlates with the risk of non‐SLN metastasis in cervical cancer.

Brazilian Society of Surgical Oncology consensus on fertility‐sparing surgery for cervical cancer

AbstractObjectiveSeveral controversies remain on conservative management of cervical cancer. Our aim was to develop a consensus recommendation on important and novel topics of fertility‐sparing treatment of cervical cancer.MethodsThe consensus was sponsored by the Brazilian Society of Surgical Oncology (BSSO) from March 2020 to September 2020 and included a multidisciplinary team of 55 specialists. A total of 21 questions were addressed and they were assigned to specialists' groups that reviewed the literature and drafted preliminary recommendations. Further, the coordinators evaluated the recommendations that were classified by the level of evidence, and finally, they were voted by all participants.ResultsThe questions included controversial topics on tumor assessment, surgical treatment, and surveillance in conservative management of cervical cancer. The two topics with lower agreement rates were the role of minimally invasive approach in radical trachelectomy and parametrial preservation. Additionally, only three recommendations had &lt;90% of agreement (fertility preservation in Stage Ib2, anti‐stenosis device, and uterine transposition).ConclusionsAs very few clinical trials have been developed in surgery for cervical cancer, most recommendations were supported by low levels of evidence. We addressed important and novel topics in conservative management of cervical cancer and our study may contribute to literature.

Clinical correlation of lymphovascular invasion and Silva pattern of invasion in early-stage endocervical adenocarcinoma: proposed binary Silva classification system

Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p<0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.

Prognostic factors in locally advanced cervical cancer with pelvic lymph node metastasis

To evaluate the prognostic impact of clinical and pathological variables and patterns of recurrence in patients with locally advanced cervical cancer with pelvic lymph node involvement (stage IIIC1 according to the 2018 FIGO Staging System). We retrospectively analyzed 62 patients with locally advanced cervical cancer treated with curative intent with radiotherapy associated with chemotherapy in AC Camargo Cancer Center from January 2007 to December 2018. Lymph node involvement was assessed by CT, MRI and positron emission tomography (PET)/CT in 28 (45.2%), 20 (32.3%) and 14 (22.6%) patients, respectively. The median tumor size was 5.0 cm and 72.6% of cases were squamous cell carcinomas. The median number of positive pelvic lymph nodes was three, and the median size of lymph nodes was 24 mm. Twenty-two (35.5%) patients had recurrence and 50% had only one site of recurrence. The sites of recurrence were pelvic, para-aortic and distant in 12 (19.4%), 6 (9.7%) and 16 (25.8%) patients, respectively. The 3 year overall and disease-free survival were 70.8% and 64.6%, respectively. Patients with adenocarcinoma had worse disease-free survival (HR 2.38; 95% CI 1.01 to 5.60; p=0.047) and overall survival (HR 2.99; 95% CI 1.14 to 7.75; p=0.025) compared with squamous cell carcinoma. In multivariate analysis, metastatic pelvic lymph node size of >2.5 cm (HR 4.38; 95% CI 1.65 to 11.6; p=0.003) and incomplete response to radiotherapy (HR 5.14; 95% CI 1.60 to 16.4; p=0.006) maintained the negative impact for overall survival. We found that pelvic lymph node size and incomplete response to radiotherapy negatively impact overall survival in patients with advanced cervical cancer with pelvic lymph node involvement. This finding may help to stratify risk in this group of patients.

Presence and extent of lymphovascular invasion in surgical stage I squamous cell carcinoma of the cervix: a comprehensive, international, multicentre, retrospective clinicopathological study

The aim of this study was to determine whether the presence and extent of lymphovascular invasion (LVI) is prognostic in surgical stage I cervical squamous cell carcinoma (SCC). All available tumour slides and/or paraffin blocks from 426 patients with stage I cervical SCC treated surgically with curative intent were collected from 18 institutions and retrospectively analysed. Presence and extent of LVI (focal <5 spaces, extensive ≥5 spaces) were assessed on scanning magnification in large haematoxylin and eosin slide sets in 366 cases. Progression-free survival (PFS) was calculated as the time from surgery to first progression or death or last follow-up, whichever occurred first. Overall survival (OS) was defined as the time from surgery to death or last follow-up. Clinicopathological and statistical analyses were performed on 97 patients with the International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IA and 329 patients with stage IB SCC of the cervix. LVI, both focal and extensive, was more frequent in stage IB than in stage IA (p<0.001). Patients with stage IB carcinomas with extensive LVI had worse PFS [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.49, 5.49; p=0.005] and OS (HR 2.88; 95% CI 1.38, 6.02; p=0.012) than those with focal or no LVI. In stage IA, in contrast, the presence and extent of LVI did not associate with PFS (p=0.926) or OS. Extensive LVI was not statistically correlated with PFS and OS in substages IA1, IA2 or IB2. PFS (HR 3.7; 95% CI 1.61, 8.46; p<0.001) and OS (HR 4.18; 95% CI 1.58, 11.04; p=0.002) in stage IB1, and PFS (HR 7.78; 95% CI 0.87, 69.82; p=0.039) in stage IB3 were diminished in the presence of extensive LVI. In conclusion, in patients with FIGO stage I cervical SCC, the presence and extent of LVI has prognostic significance in stage IB carcinoma, and quantifying LVI is recommended.

European Society of Gynaecological Oncology resource-stratified guidelines for the management of patients with cervical cancer.

In 2023, the European Society of Gynaecological Oncology (ESGO), jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP), published evidence-based guidelines for the management of patients with cervical cancer. Acknowledging that limitations exist even in high-income countries, some of these established standards of care are not applicable in clinical practice in some areas of the world. Following a global ESGO survey involving 256 clinicians from 57 countries, which pointed out potential limitations, barriers, and missing guidelines, ESGO decided to develop alternative management strategies for situations when optimal resources are unavailable or limited. A multi-disciplinary international development group consisting of 22 experts, utilizing feedback from the survey conducted mostly in low- and middle-income regions, identified potential limitations to the standards of care as defined in the updated ESGO-ESTRO-ESP guidelines published in 2023 and suggested alternative approaches. New resource-stratified guidelines on the management of women living with the human immunodeficiency virus have been newly proposed. To ensure a global perspective, the guidelines were reviewed by 188 independent international practitioners from Asia, Africa, Europe, and South, Central, and North America. These resource-stratified guidelines focus on achieving the best patient outcomes, with alternative management strategies based on expert opinions in areas with limited evidence. They should be used as a guide for the next best alternatives in multi-disciplinary care settings such as diagnostics, pathology, surgery, radiotherapy, systemic therapy, palliative care, and follow-up management. Efforts should always focus on providing optimal available care. In the absence of key resources, the primary effort should be directed toward consulting and referring patients to other facilities that provide better conditions.

Reconsidering adjuvant radiotherapy in intermediate-risk cervical cancer: findings from the CIRCOL study group

To evaluate survival outcomes associated with intermediate-risk factors in patients who underwent radical hysterectomy for cervical cancer, with a focus on the role of adjuvant radiotherapy. A multicenter retrospective cohort database comprising 1280 patients who underwent radical hysterectomy for cervical cancer was analyzed. For inclusion, patients had tumors ≤4 cm (International Federation of Gynecology and Obstetrics 2018 stages Ia2-Ib2) and were treated surgically between January 2000 and December 2017. Patients with lymph node metastasis, positive surgical margins, or parametrial involvement were excluded. Intermediate-risk factors were defined as tumor size >2 cm to ≤4 cm, stromal invasion ≥10 mm, and presence of lymphovascular space invasion. A total of 759 patients met inclusion criteria, of whom 158 (20.8%) received external beam radiotherapy. Patients who received external beam radiotherapy were older, more often underwent open surgery, and exhibited a higher incidence of adverse pathological features, including larger tumors, deeper stromal invasion, and lymphovascular space invasion. In multivariate analysis, tumor size >2 cm (HR 5.25, 95% CI 1.86 to 14.8) and stromal invasion ≥10 mm (HR 2.68, 95% CI 1.14 to 6.30) were independently associated with increased recurrence risk. No variables were independently associated with cancer-specific mortality. The presence of ≥2 intermediate-risk factors significantly increased the risk of recurrence (HR 3.48, 95% CI 2.05 to 5.91) and cancer-related death (HR 2.47, 95% CI 1.04 to 2.89), regardless of radiotherapy use. Tumor size and depth of stromal invasion were associated with increased recurrence risks. Adjuvant radiotherapy was not associated with improved survival outcomes in patients with intermediate-risk features.

Oncologic outcomes of sentinel lymph node mapping in patients with high-intermediate- and high-risk endometrial cancer: a systematic review and meta-analysis.

Sentinel lymph node (SLN) mapping has not been widely adapted in the setting of high-intermediate and high-risk endometrial cancer. The goal of this study was to determine oncologic outcomes in this high-intermediate or high-risk population undergoing SLN mapping compared with systematic pelvic ± para-aortic lymphadenectomy. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, MEDLINE, Embase, and Cochrane databases were searched for trials comparing SLN with lymphadenectomy for patients with high- or high-intermediate-risk endometrial cancer. Studies were excluded if they lacked a control group, involved overlapping populations, were only available as abstracts, or were not in English. The main outcomes were overall survival, disease-free survival, recurrence, and adjuvant therapy rates. A pre-specified sub-group analysis was carried out that included high-risk patients, high-intermediate-risk patients, and only propensity score-matched studies. Statistical analysis was performed using RStudio Version 4.4.0. Heterogeneity was assessed using I A total of 10 observational studies (2 with population data from the National Center for Biotechnology Information - NCBI and the Surveillance, Epidemiology and End Results - SEER databases) were included, evaluating a total of 6127 patients. There were no randomized control trials. There were no differences regarding overall survival (HR 0.82, 95% CI 0.60 to 1.11, p = .19, I SLN mapping is associated with similar oncologic outcomes to lymphadenectomy in patients with high-intermediate and high-risk endometrial cancer. Routine lymphadenectomy should no longer be considered a standard of care.

Prognostic value of isolated tumor cells in sentinel lymph nodes in intermediate-risk endometrial cancer: results from an international, multi-institutional study

This study assessed oncologic outcomes of patients with intermediate-risk endometrioid endometrial cancer and isolated tumor cells (ITC) (≤0.2 mm or ≤200 cells) in sentinel lymph nodes (SLNs). Patients with SLN-ITC diagnosed between 2012 and 2019 were identified from 19 centers worldwide, while SLN-negative patients were identified at Mayo Clinic, Rochester between 2014 and 2018. Only patients with endometrioid endometrial cancer and intermediate-risk factors (low-grade endometrioid histology and myometrial invasion ≥50%; high-grade endometrioid histology and myometrial invasion <50%) were included. Oncologic outcomes were evaluated by grouping patients according to prognostic factors: SLN-ITC and lymphovascular space invasion (LVSI). SLN-ITC patients with post-operative observation or vaginal brachytherapy (VB) alone were compared with similar node-negative patients. Of the 166 patients included, those with simultaneous presence of SLN-ITC and LVSI were at higher risk of non-vaginal recurrence (HR 3.73 [95% CI 1.17 to 11.84], p = .01) compared with patients who were node-negative with no LVSI. Among the 122 patients (28 SLN-ITC, 94 node-negative) who underwent post-operative observation or VB alone, 1 isolated vaginal recurrence was documented in a node-negative patient, while non-vaginal recurrence occurred in 3 of 28 (10.7%) SLN-ITC and 7 of 94 (7.4%) node-negative patients. The median follow-up was 2.4 years (interquartile range; 1.8-3.0) among the remaining 25 ITC patients and 2.8 years (interquartile range; 0.8-4.2) among the remaining 87 node-negative patients. There was no difference in non-vaginal recurrence-free survival (SLN-ITC: 87.3% [95% CI 74.7% to 100.0%] vs node-negative: 82.2% [95% CI 69.1% to 97.9%], p = .46) or overall survival (SLN-ITC: 76.4% [95% CI 54.3 to 100.0] vs node-negative: 84.5% [95% CI 75.0 to 95.2], p = .28) between the 2 cohorts. In patients with endometrioid endometrial cancer and intermediate-risk factors (including patients who received chemotherapy/external beam radiotherapy), the combination of SLN-ITC and LVSI was associated with worse prognosis compared with patients with no risk factors or only 1 risk factor. In the sub-group of patients who received post-operative observation or VB alone, SLN-ITC did not worsen prognosis relative to node-negative patients.

Outcomes of low-risk endometrial cancer with isolated tumor cells in the sentinel lymph nodes: a prospective, multi-center, single-arm, observational study (ENDO-ITC study)

It is unclear whether isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) adversely affect prognosis, especially in low-risk endometrial cancer. In a retrospective study, we showed a worse recurrence-free survival for low-risk endometrial cancer with ITCs than the node-negative group. Our aim is to evaluate whether the likelihood of disease recurrence differs between a prospective cohort of patients with low-risk endometrial cancer with ITCs and an historical cohort with negative SLNs. We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. This is a prospective, multi-center, single-arm observational study. Consecutive patients with low-risk endometrial cancer with ITCs in the SLNs will be accrued. Observation only will be suggested after surgery. We will include patients with endometrial cancer undergoing pelvic SLN biopsy and ultra-staging with the following characteristics: endometrioid histology, grades 1 to 2, <50% myometrial invasion, without substantial/extensive lympho-vascular space invasion. ITCs in SLNs are defined as tumor cell aggregates ≤0.2 mm or <200 cells. The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. With a sample size of 132 women with low-risk endometrial cancer and ITCs, a 1-sided log-rank test achieves 85% power at a 0.05 significance level to detect an HR of 2.1. The expected number of events during the study is 17.3. The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. ClinicalTrials.gov: NCT06689956.

Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study

The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

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.

Comparison of Two-Position and Four-Position Cervical Injection Techniques for Sentinel Lymph Node Mapping in Endometrial Cancer Using Methylene Blue

This clinical trial evaluates lymph node mapping in newly diagnosed endometrial cancer patients undergoing surgery. The standard technique uses a 2-point methylene blue cervical injection. The study aims to determine if increasing injection points improves mapping success.

Sentinel Node Mapping in High Risk Endometrial Cancer

This study will evaluate the role of systematic lymphadenectomy after sentinel node (SLN) mapping in high risk endometrial cancer (high grade histologies or deep myometrial invasion). The participants will be randomized in a non-inferiority controlled trial in 2 groups: SLN mapping or SLN mapping followed by systematic lymphadenectomy.