Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis.
01 May 2017-American Journal of Obstetrics and Gynecology (Am J Obstet Gynecol)-Vol. 216, Iss: 5, pp 459-476
TL;DR: Sentinel lymph node mapping is feasible and accurately predicts nodal status in women with endometrial cancer and may be considered an alternative standard of care in the staging of women with Endometrial Cancer.
About: This article is published in American Journal of Obstetrics and Gynecology.The article was published on 2017-05-01 and is currently open access. It has received 229 citations till now. The article focuses on the topics: Sentinel lymph node & Sentinel node.
Citations
More filters
Innsbruck Medical University1, The Catholic University of America2, First Faculty of Medicine, Charles University in Prague3, Copenhagen University Hospital4, University of Cologne5, University College London6, Leiden University Medical Center7, Institut Gustave Roussy8, Agostino Gemelli University Polyclinic9, Imperial College London10, University of Navarra11, Johannes Kepler University of Linz12, Erasmus University Rotterdam13, Humboldt University of Berlin14, Medical University of Vienna15, The Royal Marsden NHS Foundation Trust16, University of Amsterdam17, Dresden University of Technology18, European Institute of Oncology19
TL;DR: A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions as mentioned in this paper, and the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncologies (ESTRO), and the EPSP jointly decided to update these evidence-base guidelines and to cover new topics in order to improve the quality of care for women with endometrium carcinoma across Europe and worldwide.
Abstract: A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.
584 citations
TL;DR: Whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers is established.
Abstract: Summary Background Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers. Methods In this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed. Findings Between Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39–62; p Interpretation Indocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances. Funding Novadaq.
192 citations
TL;DR: This prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.
166 citations
Cites background from "Sentinel lymph node assessment in e..."
...which reported an overall detection rate of 81% and a bilateral detection rate of 50% when compiling data from 55 published studies on endometrial cancer SLN mapping [22]....
[...]
TL;DR: With a complete sensitivity to detect pelvic LNMs, the described pelvic SLN algorithm can, in the hands of experienced surgeons, exclude overall nodal involvement in 99% and thereby safely replace a full lymphadenectomy in HREC.
130 citations
TL;DR: Patients with endometrial cancer found to have SLN ITCs have an excellent outcome and the use of adjuvant treatment should be tailored to uterine factors and histology and not solely based on the presence of I TCs.
108 citations
References
More filters
TL;DR: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.
Abstract: BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.
1,462 citations
TL;DR: Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence, and if a prospective randomised or comparative cohort study is planned to validate the therapeutic effect ofymphadenectomy, it should include both pelvic andParalympianectomy.
650 citations
TL;DR: The Cochrane review and meta-analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early-stage endometrial cancer found no survival advantage and found no difference in risk of direct surgical morbidity between women who underwent lymphadenectomy and those who did not undergo lymphenectomy.
Abstract: Background
This is an update of a previous Cochrane review published in Issue 1, 2010 and updated in Issue 9, 2015. The role of lymphadenectomy in surgical management of endometrial cancer remains controversial. Lymph node metastases can be found in approximately 10% of women who before surgery are thought to have cancer confined to the womb. Removal of all pelvic and para-aortic lymph nodes (lymphadenectomy) at initial surgery has been widely advocated, and pelvic and para-aortic lymphadenectomy remains part of the FIGO (International Federation of Gynaecology and Obstetrics) staging system for endometrial cancer. This recommendation is based on data from studies that suggested improvement in survival following pelvic and para-aortic lymphadenectomy. However, these studies were not randomised controlled trials (RCTs), and treatment of pelvic lymph nodes may not confer a direct therapeutic benefit, other than allocating women to poorer prognosis groups. Furthermore, the Cochrane review and meta-analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early-stage endometrial cancer found no survival advantage. Surgical removal of pelvic and para-aortic lymph nodes has serious potential short-term and long-term sequelae. Therefore, it is important to investigate the clinical value of this treatment.
Objectives
To evaluate the effectiveness and safety of lymphadenectomy for the management of endometrial cancer.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to June 2009 for the original review, updated the search to June 2015 for the last updated version and further extended the search to March 2017 for this version of the review. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field.
Selection criteria
RCTs and quasi-RCTs that compared lymphadenectomy versus no lymphadenectomy in adult women diagnosed with endometrial cancer.
Data collection and analysis
Two review authors independently extracted data and assessed risk of bias. Hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received lymphadenectomy versus those with no lymphadenectomy were pooled in random-effects meta-analyses. We assessed the quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.
Main results
978 unique references were identified via the search strategy. All but 50 were excluded by title and abstract screening. Three RCTs met the inclusion criteria; for one small RCT, data were insufficient for inclusion in the meta-analysis. The two RCTs included in the analysis randomly assigned 1945 women, reported HRs for survival adjusted for prognostic factors and based on 1851 women and had an overall low risk of bias, as they satisfied four of the assessment criteria. The third study had an overall unclear risk of bias, as information provided was not adequate concerning random sequence generation, allocation concealment, blinding, or completeness of outcome reporting.
Results of the meta-analysis remained unchanged from the previous versions of this review and indicated no differences in overall and recurrence-free survival between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy (pooled hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.81 to 1.43; HR 1.23, 95% CI 0.96 to 1.58 for overall and recurrence-free survival, respectively) (1851 participants, two studies; moderate-quality evidence).
We found no difference in risk of direct surgical morbidity between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy. However, women who underwent lymphadenectomy had a significantly higher risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation than those who did not undergo lymphadenectomy (RR 3.72, 95% CI 1.04 to 13.27; RR 8.39, 95% CI 4.06 to 17.33 for risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation, respectively) (1922 participants, two studies; high-quality evidence).
Authors' conclusions
This review found no evidence that lymphadenectomy decreases risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. Evidence on serious adverse events suggests that women who undergo lymphadenectomy are more likely to experience surgery-related systemic morbidity or lymphoedema/lymphocyst formation. Currently, no RCT evidence shows the impact of lymphadenectomy in women with higher-stage disease and in those at high risk of disease recurrence.
384 citations
TL;DR: Preliminary observations confirm that the lymphatic network draining the uterus is complex and involves both pelvic and paraaortic nodes and can identify targets for selective nodal biopsy in some women.
341 citations
TL;DR: Sentinel lymph node (SLN) mapping, which has been used in other cancer types, may be an acceptable surgical strategy between a complete lymphadenectomy and no nodal evaluation in patients with endometrial cancer.
Abstract: Most patients with endometrial cancer will present with early-stage disease. Although the rate of metastasis in these patients is low, proffering excellent prognoses, the standard of treatment in many practices still includes a complete or selective pelvic and para-aortic lymphadenectomy for staging; and accurate surgical staging is the most important prognostic factor. Many patients will undergo a comprehensive lymphadenectomy despite having disease confined to the uterus, resulting in prolonged operating time, additional cost, and potential side effects, such as lower extremity lymphedema. However, recent studies show that a complete lymphadenectomy may have no therapeutic benefit in patients with early-stage endometrial cancer. Sentinel lymph node (SLN) mapping, which has been used in other cancer types, may be an acceptable surgical strategy between a complete lymphadenectomy and no nodal evaluation in patients with endometrial cancer. SLN mapping is based on the concept that lymph node metastasis is the result of an orderly process; that is, lymph drains in a specific pattern away from the tumor, and therefore, if the SLN, or first node, is negative for metastasis, then the nodes after the SLN should also be negative. This approach can help patients avoid the side effects associated with a complete lymphadenectomy, although disease must be thoroughly staged for accurate prognosis and determination of appropriate treatment approach. Surgeon experience, adherence to an SLN algorithm, and the use of pathologic "ultrastaging" are key factors for successful SLN mapping.
164 citations