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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Can mismatch repair status be added to sentinel lymph node mapping algorithm in endometrioid endometrial cancer?

OBJECTIVE: To evaluate the relation between mismatch repair (MMR) status and the risk of lymph node metastasis in endometrial cancer, and whether this additional data can be incorporated to current SLN (sentinel lymph node) algorithm. METHODS: We included a series of 332 women that underwent SLN mapping ± systematic lymphadenectomy from January 2013 to December 2021. Protein expressions of MLH1, MSH2, MSH6, PMS2 were examined by immuno-histochemistry and considered MMRd (deficient) when at least one protein was not expressed. RESULTS: MMRd was noted in 20.8% of cases and correlated to grade 3 (p = 0.018) and presence of lymphovascular space invasion (p = 0.032). Moreover, MMRd was an independent risk factor for lymph node metastasis (OR 2.76, 95% CI 1.36-5.62). Notably, 21.7% (15/69) cases with MMRd had lymph node metastasis compared to 9.5% (25/263) of cases with MMRp (proficient) (p = 0.005). The overall and bilateral SLN detection rates were 91.9% and 75.9%, respectively. Of the 80 (24%) cases of non-bilateral SLN detection, 66.2% had low-grade tumors (G1/G2) and myometrial invasion <50%. Considering MMR status an independent prognostic factor for lymph node metastasis, a systematic lymphadenectomy (side specific or bilateral) would forgo in 53.7% (43/80) of cases with non-bilateral detection, representing 13% (43/332) of all endometroid tumors. CONCLUSION: MMR status was independently related to lymph node metastasis in endometrioid EC. Moreover, MMR status may help to select patients that can forgo systematic lymphadenectomy in case of undetected SLN.

Qualidade de vida e mapeamento de complicações: avaliação do linfonodo sentinela no câncer de endométrio / Quality of life and complications: evaluation of the sentinel lymph node in endometrial cancer

Objetivo: Avaliar a incidência das complicações pós-operatórias do estadiamento cirúrgico e qualidade de vida relacionada ao protocolo do linfonodo sentinela associado ou não à linfadenectomia sistemática no tratamento do câncer do endométrio. Métodos: Foi conduzida uma coorte prospectiva entre dezembro de 2017 e abril de 2022, incluindo mulheres com carcinoma de endométrio em estágio inicial presumido (doença restrita ao útero) e com estadiamento linfonodal, agrupadas em: Grupo LNS (somente pesquisa do linfonodo sentinela) e Grupo LNS+LND (linfonodo sentinela com adição de linfadenectomia sistemática). Foram incluídas pacientes com baixo e alto risco para metástase linfonodal. As pacientes de alto risco fazem parte do estudo ALICE (NCT03366051), um estudo prospectivo randomizado de não inferioridade. As pacientes foram avaliadas no pré-operatório, 1 mês, 6 e 12 meses, com aplicação de questionário de qualidade de vida (QQV) pelo EORTC QLQ-C30 e Cx24, avaliação clínica e perimetria para avaliar linfedema. Resultados: Foram incluídas 152 mulheres, sendo 113 (74,3%) no grupo LNS e 39 (25,7%) no grupo LNS+LND. Complicações cirúrgicas intraoperatórias ocorreram em 2 (1,3%) casos todas pertencentes ao grupo LNS+LND. Complicações cirúrgicas até 30 dias foram encontradas em 29 (19,1%) casos. As pacientes submetidas a LNS+LND apresentaram taxas gerais de complicações cirúrgicas mais altas em comparação com aquelas submetidas apenas a LNS (33,3% vs. 14,2%; p=0,011). O grupo LNS+LND apresentou maior tempo de cirurgia (p=0,001) e necessidade de UTI (p=0,001). A incidência de linfocele foi encontrada em 8 casos, apenas no grupo LNS+LND (0 vs. 20,5%; p<0,001). Para o linfedema de membros inferiores, não foi encontrada diferença entre os grupos pela avaliação perimétrica do grupo LNS comparado ao LNS+LND (23,2% vs. 13,3%; p= 0,25). O mesmo ocorreu para a avaliação clínica do linfedema, encontrado em 21,2% do grupo LNS e 33,3% do grupo LNS+LND (p=0,14). Entretanto, na avaliação de presença de linfedema pelo score de sintomas do EORTC, houve maior relato de linfedema no grupo LNS+LND (score 23,52) comparado ao grupo LNS (score 12,45) na avaliação de 12 meses (p=0,02). Além disso, encontramos associação entre avaliação clínica e linfedema relatado pelo paciente. O score médio de linfedema foi maior quando este foi detectado por exame clínico em 6 meses (30,10 vs. 7,8; p<0,001) e 12 meses (36,4 vs. 6,0; p<0,001), no entanto sem associação entre perimetria e avaliações clínicas (p=0,76). Em relação à avaliação global de qualidade de vida, não houve diferença entre os grupos aos 12 meses (p=0,21). Conclusões: Houve maior taxa geral de complicações para o grupo submetido a linfadenectomia sistemática, assim como maiores taxas de linfocele e linfedema pelo score de sintomas. Nenhuma diferença foi encontrada em relação à qualidade de vida entre os grupos LNS e LNS+LND

Objectives: To evaluate the incidence of postoperative complications of surgical lymph node staging procedures and quality of life related to the sentinel lymph node protocol associated or not with systemic lymphadenectomy in the treatment of endometrial cancer. Methods: A prospective cohort was conducted between December 2017 and April 2022. Women with presumed early-stage endometrial carcinoma (disease restricted to the uterus) and with lymph node staging were included, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND Group (sentinel lymph node with addition of systematic lymphadenectomy). Patients with low and high risk for lymph node metastasis were included, and high-risk patients were part of the ALICE study (NCT03366051), a prospective randomized non-inferiority study. The patients were assessed preoperatively, 1 month, 6 and 12 months with the application of a quality-of-life questionnaire (QQL) using the EORTC QLQ-C30 and Cx24, clinical evaluation and perimetry to assess lymphedema. Results: 152 women were included, 113 (74.3%) women in the SLN group and 39 (25.7%) in the SLN+LND group. Intraoperative surgical complications occurred in 2 (1.3%) cases, all of them in the SLN+LND group. Surgical complications within 30 days were found in 29 (19.1%) cases. Patients undergoing SLN+LND had higher overall rates of surgical complications compared to women undergoing SLN alone (33.3% vs. 14.2%; p=0.011). The SLN+LND group had longer surgery time (p=0.001) and need for ICU (p=0.001). The incidence of lymphocele was found in 8 cases and only in the SLN+LND group (0 vs. 20.5%; p<0.001). For lower limbs lymphedema, no difference was found between the groups by the perimetric evaluation of the SLN group compared to the SLN+LND (23.2% vs. 13.3%; p=0.25). The same occurred for the clinical evaluation of lymphedema, being found in 21.2% for the SLN group and 33.3% for the SLN+LND group (p=0.14). However, when evaluating the presence of lymphedema using the EORTC symptom score, there was a higher number of lymphedema reports in the SLN+LND group (score 23.52) compared to the SLN group (score 12.45) at the 12-month evaluation (p=0.02). In addition, we found an association between clinical evaluation and lymphedema reported by the patient. The lymphedema score had a higher mean score when lymphedema was detected by clinical examination at 6 months (30.10 vs. 7.8; p<0.001) and 12 months (36.4 vs. 6.0; p<0.001), however with no association between perimetry and clinical evaluations (p=0.76). Regarding the overall assessment of quality of life, there was no difference between the groups at 12 months (p=0.21). Conclusions: 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 regarding quality of life between the LNS and LNS+LND groups

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

BACKGROUND: 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. PRIMARY OBJECTIVES: The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. STUDY HYPOTHESIS: 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. TRIAL DESIGN: 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. MAJOR INCLUSION AND EXCLUSION CRITERIA: 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. PRIMARY ENDPOINTS: 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. SAMPLE SIZE: 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. TRIAL REGISTRATION NUMBER: NCT03366051.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Survival outcomes were similar between minimally invasive and open radical hysterectomy in this large retrospective multicenter cohort.

Predictive Factors for Residual Disease After Conization in Cervical Cancer.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Our data suggest that SLN mapping independently decreases the risk of lymphocele formation compared with full lymphadenectomy in EC.

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

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer.

BACKGROUND: This study aimed to determine the impact of sentinel lymph node (SLN)-mapping on the staging of high-risk endometrial cancer (endometrioid grade 3, serous, clear cell, carcinosarcoma, deep myometrial invasion, or angiolymphatic invasion). METHODS: The study analyzed a series of 236 patients treated at AC Camargo Cancer Center from June 2007 to February 2017. The compared 75 patients who underwent SLN-mapping (SLN group) with 161 patients who received pelvic ± para-aortic lymphadenectomy (N-SLN group). Patients with adnexal, peritoneal, or suspicious node metastases were excluded from the study. RESULTS: The groups did not differ in terms of age, histologic type, or presence of deep myometrial invasion. The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60% of the patients. Of 20 positive SLNs, 8 (40%) were detected only after immunohistochemistry (IHC). The findings showed an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false-negative predictive value of 4.3%. The SLN group had more pelvic node metastases detected than the N-SLN group (26.7 vs 14.3%; p = 0.02). However, the rate of para-aortic node metastases did not differ between the two groups (13.5 vs 5.6%; p = 0.12). Five patients (3.5%) in the N-SLN group had isolated para-aortic node metastases versus none in the patients with SLN mapped. Additionally, the SLN group received more adjuvant chemotherapy (48 vs 33.5%; p = 0.03). CONCLUSIONS: The data suggest that SLN-mapping identifies more pelvic node metastases than lymph node dissection alone and increases the node detection rate by 12.5% after IHC. Furthermore, no isolated para-aortic node metastases are observed when SLN is detected.