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OBJECTIVE: Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. METHODS: The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. RESULTS: Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). CONCLUSIONS: Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.
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BACKGROUND: Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. PATIENTS AND METHODS: A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. RESULTS: A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. CONCLUSIONS: In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.
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Neoplasias Endometriales , Ganglio Linfático Centinela , Femenino , Humanos , Biopsia del Ganglio Linfático Centinela , Ganglios Linfáticos/patología , Micrometástasis de Neoplasia/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Escisión del Ganglio LinfáticoRESUMEN
OBJECTIVE: It has been suggested that the manipulation of neoplastic tissue during hysteroscopy may lead to dissemination of tumor cells into the peritoneal cavity and worsen prognosis and overall survival. The goal of this study was to assess the oncological safety comparing hysteroscopy to Pipelle blind biopsy in the presurgical diagnosis of patients with endometrial cancer. METHODS: We performed a retrospective multicentric study among patients who had received primary surgical treatment for endometrial cancer. A multivariate statistical analysis model was used to compare relapse and survival rates in patients who had been evaluated preoperatively either by hysteroscopy or Pipelle biopsy. The relapse rate, disease-free survival, and overall survival were assessed as the main outcomes. The histological type, tumor size, myometrial invasion, International Federation of Gynecology and Obstetrics (FIGO) stage, surgical approach, use of a uterine manipulator, and adjuvant treatment were also included in the analysis. RESULTS: A total of 1731 women from 15 centers were included: 1044 in the hysteroscopy group and 687 in the Pipelle sampling group. 225 patients relapsed during the 10 year follow-up period: 139 (13.3%) in the hysteroscopy group and 86 (12.4%) in the Pipelle sampling group. There is no evidence of an association between the use of hysteroscopy as a diagnostic method and relapse rate (HR 1.24, 95% CI 0.92 to 1.66; p=0.16), lower disease-free survival (HR 1.23, 95% CI 0.92 to 1.66; p=0.15), or overall survival (HR 0.95, 95% CI 0.70 to 1.29; p=0.76). CONCLUSION: Hysteroscopy is a safe diagnostic method for patients with endometrial cancer with no impact on oncological outcomes when compared with sampling by Pipelle.
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BACKGROUND: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. OBJECTIVE: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. STUDY DESIGN: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. RESULTS: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27-4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I-II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57-0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07-2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63). CONCLUSION: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I-II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results.
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Neoplasias Endometriales/cirugía , Histerectomía/instrumentación , Recurrencia Local de Neoplasia/cirugía , Anciano , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/cirugía , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , España , Resultado del TratamientoAsunto(s)
Neoplasias Endometriales , Ganglio Linfático Centinela , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela , Escisión del Ganglio Linfático , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Estadificación de NeoplasiasRESUMEN
PURPOSE: The main goal of this study is to assess the impact of tumor manipulation on the presence of lympho-vascular space invasion and its influence on oncological results. METHODS: We performed a retrospective multi-centric study amongst patients who had received primary surgical treatment for apparently early-stage endometrial cancer. A multivariate statistical analysis model was designed to assess the impact that tumor manipulation (with the use of uterine manipulator or preoperative hysteroscopy) has on lympho-vascular development (LVSI) in the final surgical specimen. RESULTS: A total of 2852 women from 15 centers were included and divided into two groups based on the lympho-vascular status in the final surgical specimen: 2265 (79.4%) had no LVSI and 587 (20.6%) presented LVSI. The use of uterine manipulator was associated with higher chances of lympho-vascular involvement regardless of the type used: Balloon manipulator (HR: 95% CI 4.64 (2.99-7.33); p < 0.001) and No-Balloon manipulator ([HR]: 95% CI 2.54 (1.66-3.96); p < 0.001). There is no evidence of an association between the use of preoperative hysteroscopy and higher chances of lympho-vascular involvement (HR: 95% CI 0.90 (0.68-1.19); p = 0.479). CONCLUSION: Whilst performing common gynecological procedures, iatrogenic distention and manipulation of the uterine cavity are produced. Our study suggests that the use of uterine manipulator increases the rate of LVSI and, therefore, leads to poorer oncological results. Conversely, preoperative hysteroscopy does not show higher rates of LVSI involvement in the final surgical specimen and can be safely used.
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The main aim is to compare oncological outcomes and patterns of recurrence of patients with early-stage endometrioid endometrial cancer according to lymphovascular space invasion (LVSI) status. The secondary objective is to determine preoperative predictors of LVSI. We performed a multicenter retrospective cohort study. A total of 3546 women diagnosed with postoperative early-stage (FIGO I-II, 2009) endometrioid endometrial cancer were included. Co-primary endpoints were disease-free survival (DFS), overall survival (OS), and pattern of recurrence. Cox proportional hazard models were used for time-to-event analysis. Univariate and multivariate logistical regression models were employed. Positive LVSI was identified in 528 patients (14.6%) and was an independent prognostic factor for DFS (HR 1.8), OS (HR 2.1) and distant recurrences (HR 2.37). Distant recurrences were more frequent in patients with positive LVSI (78.2% vs. 61.3%, p < 0.01). Deep myometrial invasion (OR 3.04), high-grade tumors (OR 2.54), cervical stroma invasion (OR 2.01), and tumor diameter ≥ 2 cm (OR 2.03) were independent predictors of LVSI. In conclusion, in these patients, LVSI is an independent risk factor for shorter DFS and OS, and distant recurrence, but not for local recurrence. Deep myometrial invasion, cervical stroma invasion, high-grade tumors, and a tumor diameter ≥ 2 cm are independent predictors of LVSI.
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PURPOSE: The main goal of this study is to assess the diagnostic agreement between preoperative biopsy and definitive histology of the surgical specimen to determine which sampling method is most suitable for diagnosis of early-stage endometrial cancer. METHODS: We performed a retrospective multicentric study to assess the correlation between three endometrial sampling methods (hysteroscopy, pipelle and D&C) in patients who had undergone preoperative endometrial biopsy and received primary surgical treatment for endometrial cancer. The primary objective was the agreement rate between hysteroscopy (HSC), endometrial biopsy (pipelle) and dilatation and curettage (D&C). RESULTS: A total of 1833 women who underwent preoperative sampling at 15 centers were included: 1042 biopsies were performed by HSC, 703 by pipelle and 88 by D&C. All three methods presented a moderate diagnostic concordance (κ = 0.40-0.61) with the definitive specimen's histology: HSC (κ = 0.47), pipelle sampling (κ = 0.48) and D&C (κ = 0.48). Likewise, a subgroup analysis was performed by histological subtype comparing HSC and endometrial biopsy, showing that neither is superior as a diagnostic method. CONCLUSIONS: According to this study, the use of pipelle sampling could become an adequate diagnostic method in endometrial cancer due to its similar agreement to HSC, ease of use and affordability.