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Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis

Published:November 18, 2016DOI:https://doi.org/10.1016/j.ajog.2016.11.1033

      Background

      In the staging of endometrial cancer, controversy remains regarding the role of sentinel lymph node mapping compared with other nodal assessment strategies.

      Objective

      We conducted a systematic review to evaluate the diagnostic accuracy and clinical impact of sentinel lymph node mapping in the management of endometrial cancer.

      Data Sources

      We searched Medline, Embase, and the Cochrane Central Registry of Controlled trials for studies published in English before March 25, 2016 (PROSPERO CRD42016036503).

      Study Eligibility Criteria

      Studies were included if they contained 10 or more women with endometrial cancer and reported on the detection rate, sensitivity, and/or impact on treatment or survival of sentinel lymph node mapping.

      Study Appraisal and Synthesis Methods

      Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality. The detection rate, sensitivity, and factors associated with successful mapping (study size, body mass index, tumor histology and grade, injection site, dye type) were synthesized through random-effects meta-analyses and meta-regression.

      Results

      We identified 55 eligible studies, which included 4915 women. The overall detection rate of sentinel lymph node mapping was 81% (95% confidence interval, 77–84) with a 50% (95% confidence interval, 44–56) bilateral pelvic node detection rate and 17% (95% confidence interval, 11–23) paraaortic detection rate. There was no difference in detection rates by patient body mass index or tumor histology and grade. Use of indocyanine green increased the bilateral detection rate compared with blue dye. Additionally, cervical injection increased the bilateral sentinel lymph node detection rate but decreased the paraaortic detection rate compared with alternative injection techniques. Intraoperative sentinel lymph node frozen section increased the overall and bilateral detection rates. The sensitivity of sentinel node mapping to detect metastases was 96% (95% confidence interval, 91–98); ultrastaging did not improve sensitivity. Compared with women staged with complete lymphadenectomy, women staged with sentinel lymph node mapping were more likely to receive adjuvant treatment.

      Conclusion

      Sentinel lymph node mapping is feasible and accurately predicts nodal status in women with endometrial cancer. The current data favors the use of cervical injection techniques with indocyanine green. Sentinel lymph mapping may be considered an alternative standard of care in the staging of women with endometrial cancer.

      Key words

      Endometrial cancer is the most common gynecological malignancy in the United States, with its incidence increasing because of rising obesity rates.
      • Morice P.
      • Leary A.
      • Creutzberg C.
      • Abu-Rustum N.
      • Darai E.
      Endometrial cancer.
      Lymph node status is the most important predictor of survival and also guides postoperative treatment planning.
      • Sharma C.
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      • Lewin S.N.
      • et al.
      Lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancer.
      Whereas evaluation of lymph nodes has been included in surgical staging criteria for endometrial cancer since 1988, the optimal procedure for lymph node assessment is controversial. Performance of pelvic and paraaortic lymphadenectomy (LND) has been associated with improved survival in cohort studies, but 2 randomized controlled trials demonstrated no impact on survival.
      • Frost J.A.
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      • Sakuragi N.
      Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis.
      For high-grade histologies of endometrial cancer, LND remains relevant, given the greater risk of nodal involvement and recurrence associated with these histologies.
      • Todo Y.
      • Kato H.
      • Kaneuchi M.
      • Watari H.
      • Takeda M.
      • Sakuragi N.
      Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis.
      However, because there are risks of lymphedema and intraoperative complications associated with LND, many gynecological oncologists omit LND in select patients with endometrial cancer.
      • Fotopoulou C.
      • Kraetschell R.
      • Dowdy S.
      • et al.
      Surgical and systemic management of endometrial cancer: an international survey.
      Sentinel lymph node (SLN) mapping has been proposed as a technique to identify lymph node metastases while reducing the surgical morbidity associated with complete LND.
      • Abu-Rustum N.R.
      Sentinel lymph node mapping for endometrial cancer: a modern approach to surgical staging.
      An SLN is defined as the first node to receive drainage from a primary tumor and is the most likely to harbor metastases in cancers with lymphatic spread. SLN mapping may also detect aberrant lymphatic drainage that would be missed on routine LND. SLN mapping is established as the standard of care for the staging of breast cancer and melanoma among other cancers.
      • Mansel R.E.
      • Fallowfield L.
      • Kissin M.
      • et al.
      Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.
      • Niebling M.G.
      • Pleijhuis R.G.
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      • Brouwers A.H.
      • van Dam G.M.
      • Hoekstra H.J.
      A systematic review and meta-analyses of sentinel lymph node identification in breast cancer and melanoma, a plea for tracer mapping.
      However, adapting its use in endometrial cancer has been more challenging, given the complexity and bilaterality of the nodal basins that drain the uterus.
      Whereas early results for SLN mapping in endometrial cancer were promising, other research has raised concerns about the adequacy of nodal detection, especially for paraaortic nodes.
      • Kang S.
      • Yoo H.J.
      • Hwang J.H.
      • Lim M.-C.
      • Seo S.-S.
      • Park S.-Y.
      Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies.
      • Cormier B.
      • Rozenholc A.T.
      • Gotlieb W.
      • Plante M.
      • Giede C.
      Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research.
      Moreover, body mass index (BMI) may limit the lymphatic spread of tracers used in SLN mapping, which could limit its efficacy in endometrial cancer.
      • Torné A.
      • Pahisa J.
      • Vidal-Sicart S.
      • et al.
      Transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR): a new method for sentinel lymph node detection in endometrial cancer.
      • Tanner E.J.
      • Sinno A.K.
      • Stone R.L.
      • Levinson K.L.
      • Long K.C.
      • Fader A.N.
      Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer.
      For these reasons, current guidelines do not yet recommend SLN mapping as the standard of care in the staging of this malignancy, although national societies and organizations that define treatment standards are increasingly recognizing the utility of this staging approach. For instance, the National Comprehensive Cancer Network states that “selected patients with apparent uterine-confined endometrial carcinoma may be candidates for sentinel lymph node mapping … the expertise of the surgeon and attention to technical detail is critical.”

      Fayna Ferkle N, Nicole McMillian P, Jillian Scavone M, et al. NCCN guidelines index uterine neoplasms TOC discussion NCCN guidelines, version 2. 2016 panel members uterine neoplasms MD/liaison, Dana-Farber/Brigham and Women’s Cancer Center. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed May 30, 2016.

      Nonetheless, the last meta-analysis of SLN mapping outcomes in endometrial cancer was conducted in 2012.
      • Ansari M.
      • Rad M.A.G.
      • Hassanzadeh M.
      • et al.
      Sentinel node biopsy in endometrial cancer: systematic review and meta-analysis of the literature.
      Since that time, numerous studies have been published, demonstrating major advances in SLN technology and techniques.
      • Zhang X.
      • Li Y.
      • Zhou Y.
      • et al.
      Diagnostic performance of indocyanine green-guided sentinel lymph node biopsy in breast cancer: a meta-analysis.
      A contemporary understanding of SLN detection rates and technique limitations is critical to advancing surgical staging standards and optimizing mapping in this setting. Thus, the objectives of this systematic review and meta-analysis are as follows: (1) to evaluate the diagnostic accuracy of SLN mapping for the staging of endometrial cancer, (2) to analyze factors associated with the diagnostic accuracy of SLN mapping, and (3) to assess the clinical impact of SLN detection in the management of endometrial cancer.

      Materials and Methods

      Search strategy

      We searched Medline, Embase, and the Cochrane Library from database inception to March 25, 2016. Electronic searches were supplemented by reviewing reference lists of included studies and prior systematic reviews, hand-searching the journal Gynecologic Oncology, and contacting the authors of included studies for any additional published or unpublished studies meeting review inclusion criteria. When the search strategy identified a meeting abstract, we searched Medline for an associated full-text article by the same author group. We developed search terms based on prior systematic reviews and input from a reference librarian (Table 1). We limited articles to English language only.
      Table 1Search terms
      Search engines
      PubMedEmbaseCochrane Library
      ([Sentinel lymph node biopsy) [mesh] or (sentinel and node*) or (sentinel and lymph*) or (lymphatic mapping) or (sentinel and biops*]) and ([endometri* or uterus or uterine or corpus uteri) and (neoplasm* or cancer or cancers or carcinoma* or malignanc* or tumor or tumors) or endometrial neoplasms [mesh] or uterine neoplasms [mesh] or “endometrial stromal tumors [mesh]])Endometrium cancer/exp or uterus cancer/exp or endometri* or uterus or uterine or corpus uteri and (neoplasm* or cancer* or carcinoma* or malignanc* or tumor*) and (sentinel and lymph* or (sentinel and node*) or (sentinel and biops*) or (sentinel and (dissection* or excision* or removal)) or (lymphatic and mapping) or sentinel lymph node biopsy/exp or sentinel lymph node/exp)1. Sentinel and ([lymph or node* or biops*]) or lymphatic mapping

      2. (endometri* or uterus or uterine or corpus uteri) and (neoplasm* or cancer or cancers or carcinoma* or malignanc* or tumor or tumors)

      3. 1 and 2
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      Details of the review protocol were registered on PROSPERO, an international database of prospectively registered systematic reviews, and can be accessed at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016036503.

      Inclusion/exclusion criteria

      Studies were included if they had the following criteria: (1) included 10 or more women diagnosed with International Federation of Gynecology and Obstetrics stage 1 or higher endometrial cancer; (2) examined the diagnostic accuracy and/or clinical impact of sentinel lymph node mapping; and (3) reported outcomes measures including, but not limited to detection rate, sensitivity, negative predictive value, adverse events, treatment impact, overall survival, and/or progression-free survival.
      We included all ages, tumor history, grade and stage, and all techniques and settings of sentinel node detection and dissection. We excluded studies with fewer than 10 women with endometrial cancer and meeting abstracts, reviews, case reports, or editorials. To avoid overlapping patient data in publications on the same cohort, we included the articles with the largest sample size.
      After removal of duplicates using Mendeley, 2 reviewers screened titles and abstracts for initial eligibility assessment. After abstract screening, 2 reviewers reviewed full-text articles for inclusion/exclusion. Review agreement was assessed with the kappa statistic, and disagreements were resolved by consensus.

      Data extraction and quality assessment

      Data were extracted by 2 independent reviewers using a standardized form. These data consisted of author, year of publication, study setting, study design, patient population, SLN technique, available outcome data, adverse events, and items for quality assessment. For the SLN technique, we extracted data on surgical approach (robotic, laparoscopic, laparotomy), use of preoperative lymphoscintigraphy, injection site (cervical vs intrauterine), use of a radioactive tracer, use of indocyanine green or blue dye, and histological assessment of SLN with intraoperative frozen section or ultrastaging.
      Ultrastaging was defined as any additional processing of sentinel lymph nodes beyond routine lymph node evaluation and often included additional sectioning and staining of SLNs with hematoxylin and eosin (H&E) dye; all cases using immunohistochemistry were considered to use ultrastaging. Two reviewers independently assessed the risk of bias in included studies using the QUADAS-2 tool. Differences were resolved through review of the original articles.
      Because the uterus is a central organ and drains to bilateral nodal basins in the pelvis, we examined SLN detection rates by patient and by hemipelvis (defined as side-specific detection) as previously described in the literature.
      • Abu-Rustum N.R.
      Sentinel lymph node mapping for endometrial cancer: a modern approach to surgical staging.
      • Kang S.
      • Yoo H.J.
      • Hwang J.H.
      • Lim M.-C.
      • Seo S.-S.
      • Park S.-Y.
      Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies.
      We defined the overall detection rate as the percentage of patients undergoing SLN procedures in which at least 1 sentinel node was identified on either side of an individual patient’s hemipelvis and the bilateral detection rate as the percentage of patients with at least 1 sentinel node identified in each hemipelvis of an individual patient.
      We defined the paraaortic detection rate as the percentage of patients undergoing SLN procedures in which at least 1 paraaortic node was identified on either side of an individual patient’s hemipelvis. Occasionally nonlymphatic tissue is harvested during SLN mapping, and we excluded these nonnodal samples from SLN detection rates when reported.
      We defined sensitivity as the percentage of patients with at least 1 positive SLN divided by all patients with successful lymph node detection and lymph node metastases. Given the impossibility of false-positive results (eg, any SLN with metastases is a positive node), specificity was defined as 100%.

      Analysis

      We used Stata 11.0 (StataCorp, College Station, TX) to conduct aggregate data random-effects meta-analyses and evaluate heterogeneity of the included studies. We calculated overall, bilateral, side-specific, and paraaortic detection rates, sensitivity, and negative predictive value estimates from data provided in the source papers. We conducted meta-analyses of detection rates using a random-effects model.
      For sensitivity, we used a bivariate mixed-effects binomial regression model for the meta-analysis.
      • Dwamena B.A.
      Midas: a program for meta-analytical integration of diagnostic accuracy studies in Stata.
      We used stratified bivariate meta-analyses and meta-regression to explore heterogeneity in effect estimates, according to study size, patient average BMI, tumor (histology, grade), and SLN technique (surgical approach, use of preoperative lymphoscintigraphy, injection site, radioactive tracer, use of dye and radioactive tracer, indocyanine green dye usage, intraoperative frozen section) characteristics. When studies reported results for multiple subgroups (eg, comparing dyes), we included the total rate in the main meta-analysis and the subgroup rates in the stratified meta-analyses and meta-regressions.
      We assessed heterogeneity among the studies using the I2 statistic and visual inspection of funnel plots.

      Results

      Of the 1230 abstracts screened, 55 articles including 4915 women with endometrial cancer were eligible for inclusion (Figure 1).
      • Torné A.
      • Pahisa J.
      • Vidal-Sicart S.
      • et al.
      Transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR): a new method for sentinel lymph node detection in endometrial cancer.
      • Tanner E.J.
      • Sinno A.K.
      • Stone R.L.
      • Levinson K.L.
      • Long K.C.
      • Fader A.N.
      Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer.
      • Allameh T.
      • Hashemi V.
      • Mohammadizadeh F.
      • Behnamfar F.
      Sentinel lymph node mapping in early stage of endometrial and cervical cancers.
      • Altgassen C.
      • Pagenstecher J.
      • Hornung D.
      • Diedrich K.
      • Hornemann A.
      A new approach to label sentinel nodes in endometrial cancer.
      • Ballester M.
      • Naoura I.
      • Chereau E.
      • et al.
      Sentinel node biopsy upstages patients with presumed low- and intermediate-risk endometrial cancer: results of a multicenter study.
      • Basta A.
      • Pityński K.
      • Basta P.
      • Hubaiewska-Hoła A.
      • Opławski M.
      • Przeszlakowski D.
      Sentinel node in gynaecological oncology.
      • Bats A.-S.
      • Clement D.
      • Larousserie F.
      • et al.
      Does sentinel node biopsy improve the management of endometrial cancer? Data from 43 patients.
      • Buda A.
      • Crivellaro C.
      • Elisei F.
      • et al.
      Impact of indocyanine green for sentinel lymph node mapping in early stage endometrial and cervical cancer: comparison with conventional radiotracer Tc and/or blue dye.
      • Burke T.W.
      • Levenback C.
      • Tornos C.
      • Morris M.
      • Wharton J.T.
      • Gershenson D.M.
      Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high- risk endometrial cancer: results of a pilot study.
      • Daraï E.
      • Dubernard G.
      • Bats A.-S.
      • et al.
      Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study.
      • Delaloye J.-F.
      • Pampallona S.
      • Chardonnens E.
      • et al.
      Intraoperative lymphatic mapping and sentinel node biopsy using hysteroscopy in patients with endometrial cancer.
      • Desai P.H.
      • Hughes P.
      • Tobias D.H.
      • et al.
      Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC).
      • Eitan R.
      • Sabah G.
      • Krissi H.
      • et al.
      Robotic blue-dye sentinel lymph node detection for endometrial cancer—factors predicting successful mapping.
      • St Clair C.M.
      • Eriksson A.G.Z.
      • Ducie J.A.
      • et al.
      Low-volume lymph node metastasis discovered during sentinel lymph node mapping for endometrial carcinoma.
      • Farghali M.M.
      • Allam I.S.
      • Abdelazim I.A.
      • et al.
      Accuracy of sentinel node in detecting lymph node metastasis in primary endometrial carcinoma.
      • Favero G.
      • Pfiffer T.
      • Ribeiro A.
      • et al.
      Laparoscopic sentinel lymph node detection after hysteroscopic injection of technetium-99 in patients with endometrial cancer.
      • Ferraioli D.
      • Chopin N.
      • Beurrier F.
      • Carrabin N.
      • Buenerd A.
      • Mathevet P.
      The incidence and clinical significance of the micrometastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.
      • Fersis N.
      • Gruber I.
      • Relakis K.
      • et al.
      Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.
      • Frumovitz M.
      • Bodurka D.C.
      • Broaddus R.R.
      • et al.
      Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.
      • Gien L.T.
      • Kwon J.S.
      • Carey M.S.
      Sentinel node mapping with isosulfan blue dye in endometrial cancer.
      • Holloway R.W.
      • Gupta S.
      • Stavitzski N.M.
      • et al.
      Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.
      • Holub Z.
      • Jabor A.
      • Lukac J.
      • Kliment L.
      Laparoscopic detection of sentinel lymph nodes using blue dye in women with cervical and endometrial cancer.
      • How J.
      • Lau S.
      • Press J.
      • et al.
      Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study.
      • How J.
      • Gotlieb W.H.
      • Press J.Z.
      • et al.
      Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer.
      • Kadkhodayan S.
      • Shiravani Z.
      • Hasanzadeh M.
      • et al.
      Lymphatic mapping and sentinel node biopsy in endometrial cancer—a feasibility study using cervical injection of radiotracer and blue dye.
      • Koskas M.
      • Chereau E.
      • Ballester M.
      • et al.
      Accuracy of a nomogram for prediction of lymph-node metastasis detected with conventional histopathology and ultrastaging in endometrial cancer.
      • Kuru O.
      • Topuz S.
      • Sen S.
      • Iyibozkurt C.
      • Berkman S.
      Sentinel lymph node biopsy in endometrial cancer: description of the technique and preliminary results.
      • Laios A.
      • Volpi D.
      • Tullis I.D.C.
      • et al.
      A prospective pilot study of detection of sentinel lymph nodes in gynaecological cancers using a novel near infrared fluorescence imaging system.
      • Lelievre L.
      • Camatte S.
      • Le Frere-belda M.A.
      • et al.
      Sentinel lymph node biopsy in cervix and corpus uteri cancers.
      • Li B.
      • Wu L.
      • Li X.
      • et al.
      Sentinel lymph node identification in endometrial cancer.
      • Lopes L.A.F.
      • Nicolau S.M.
      • Baracat F.F.
      • et al.
      Sentinel lymph node in endometrial cancer.
      • Lopez-De la Manzanara Cano C.
      • Cordero Garcia J.M.
      • et al.
      Sentinel lymph node detection using 99mTc combined with methylene blue cervical injection for endometrial cancer surgical management: a prospective study.
      • Mais V.
      • Peiretti M.
      • Gargiulo T.
      • Parodo G.
      • Cirronis M.G.
      • Melis G.B.
      Intraoperative sentinel lymph node detection by vital dye through laparoscopy or laparotomy in early endometrial cancer.
      • Mucke J.
      • Klapdor R.
      • Schneider M.
      • et al.
      Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.
      • Niikura H.
      • Kaiho-Sakuma M.
      • Tokunaga H.
      • et al.
      Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer.
      • Paley P.J.
      • Veljovich D.S.
      • Press J.Z.
      • Isacson C.
      • Pizer E.
      • Shah C.
      A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging.
      • Pandit-Taskar N.
      • Gemignani M.L.
      • Lyall A.
      • Larson S.M.
      • Barakat R.R.
      • Abu Rustum N.R.
      Single photon emission computed tomography SPECT-CT improves sentinel node detection and localization in cervical and uterine malignancy.
      • Papadia A.
      • Imboden S.
      • Siegenthaler F.
      • et al.
      Laparoscopic indocyanine green sentinel lymph node mapping in endometrial cancer.
      • Pelosi E.
      • Arena V.
      • Baudino B.
      • et al.
      Pre-operative lymphatic mapping and intra-operative sentinel lymph node detection in early stage endometrial cancer.
      • Mosgaard B.J.
      • Skovlund V.R.
      • Hendel H.W.
      Promising results using sentinel node biopsy as a substitute for radical lymphadenectomy in endometrial cancer staging.
      • Raspagliesi F.
      • Ditto A.
      • Kusamura S.
      • et al.
      Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study.
      • Robova H.
      • Charvat M.
      • Strnad P.
      • et al.
      Lymphatic mapping in endometrial cancer: comparison of hysteroscopic and subserosal injection and the distribution of sentinel lymph nodes.
      • Sawicki S.
      • Lass P.
      • Wydra D.
      Sentinel Lymph Node Biopsy in Endometrial Cancer–Comparison of 2 Detection Methods.
      • Schiavone M.B.
      • Zivanovic O.
      • Zhou Q.
      • et al.
      Survival in patients with uterine carcinosarcoma undergoing sentinel lymph node mapping.
      • Solima E.
      • Martinelli F.
      • Ditto A.
      • et al.
      Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer.
      • Touhami O.
      • Trinh X.-B.
      • Gregoire J.
      • et al.
      Is a more comprehensive surgery necessary in patients with uterine serous carcinoma?.
      • Touhami O.
      • Trinh X.-B.B.
      • Grégoire J.
      • et al.
      Predictors of non-sentinel lymph node metastasis in patients with positive sentinel lymph node (SLN) in endometrial cancer.
      • Valha P.
      • Kucera E.
      • Sak P.
      • Stepanek O.
      • Michal M.
      Intraoperative subserosal approach to label sentinel nodes in intermediate and high-risk endometrial cancer.
      • Vidal F.
      • Leguevaque P.
      • Motton S.
      • et al.
      Evaluation of the sentinel lymph node algorithm with blue dye labeling for early-stage endometrial cancer in a multicentric setting.
      • Naaman Y.
      • Pinkas L.
      • Roitman S.
      • et al.
      The added value of SPECT/CT in sentinel lymph nodes mapping for endometrial carcinoma.
      • Eriksson A.G.Z.
      • Ducie J.
      • Ali N.
      • et al.
      Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.
      • Li B.
      • Li X.
      • Wu L.
      • et al.
      A pilot study of sentinel lymph nodes identification in patients with endometrial cancer.
      The kappa statistic for interrater reliability was 96%. Twenty-one studies were conducted in North America, 23 in Europe, 6 in the Middle East, 3 in Asia, and 2 in South America (Table 2). Most studies included SLN mapping followed by completion pelvic LND with or without paraaortic LND for high-grade or nonendometrioid histology endometrial cancer as the comparison. The majority of studies were prospective (87%) with consecutive patient enrollment (87%) (Appendix Table 1).
      Figure thumbnail gr1
      Figure 1Flow diagram of study selection
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      Table 2Characteristics of included studies
      Author, yearCountryStudy sizeStudy methodTime periodCancer histologyTracer usedInjection siteRoute of surgeryReference standardPathology assessment
      Allameh et al, 2015
      • Allameh T.
      • Hashemi V.
      • Mohammadizadeh F.
      • Behnamfar F.
      Sentinel lymph node mapping in early stage of endometrial and cervical cancers.
      Iran15ProspectiveNovember 2012 through February 2014AllTc-99m and patent blueUterineOpenLNDH&E, IHC, ultrastaging
      Altgassen et al, 2007
      • Altgassen C.
      • Pagenstecher J.
      • Hornung D.
      • Diedrich K.
      • Hornemann A.
      A new approach to label sentinel nodes in endometrial cancer.
      Germany25Prospective4/2004-3/2006AllPatent blueUterineOpenPelvic LND if tumor size (>2 cm), grading (>G1), and invasion (>IA), paraaortic LND if intraoperative state sufficientH&E
      Ballester et al, 2013
      • Ballester M.
      • Naoura I.
      • Chereau E.
      • et al.
      Sentinel node biopsy upstages patients with presumed low- and intermediate-risk endometrial cancer: results of a multicenter study.
      France85RetrospectiveJuly 2002 through March 2009AllPatent blueCervicalLaparoscopicComplete pelvic LND, paraaortic LND if high-risk endometrial cancer or metastatic pelvic SLN at intraoperative or definitive histologyH&E, IHC, ultrastaging
      Basta et al, 2005
      • Basta A.
      • Pityński K.
      • Basta P.
      • Hubaiewska-Hoła A.
      • Opławski M.
      • Przeszlakowski D.
      Sentinel node in gynaecological oncology.
      Poland36NRNRNRBlue dye +/- Tc-99m, ICGCervical & UterineNRLNDIHC, ultrastaging
      Bats et al, 2008
      • Bats A.-S.
      • Clement D.
      • Larousserie F.
      • et al.
      Does sentinel node biopsy improve the management of endometrial cancer? Data from 43 patients.
      France43ProspectiveJanuary 2002 through March 2006AllIsosulfan blueCervicalLaparoscopicPelvic and paraaortic LND if stage IC cancer as assessed based on the depth of myometrial invasion on the preoperative MRI scan, pelvic node involvement, adnexal involvement, and serous carcinoma histologyH&E, IHC, ultrastaging
      Buda et al, 2016
      • Buda A.
      • Crivellaro C.
      • Elisei F.
      • et al.
      Impact of indocyanine green for sentinel lymph node mapping in early stage endometrial and cervical cancer: comparison with conventional radiotracer Tc and/or blue dye.
      Italy118RetrospectiveOctober 2010 through May 2015AllTc-99m sulfur, patent blueCervicalLaparoscopicComplete Pelvic LND, paraaortic LND if positive preoperative PET/CT and in absence of SLN mapping or unilateral mappingH&E, IHC, ultrastaging
      Burke et al, 1996
      • Burke T.W.
      • Levenback C.
      • Tornos C.
      • Morris M.
      • Wharton J.T.
      • Gershenson D.M.
      Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high- risk endometrial cancer: results of a pilot study.
      United States15ProspectiveNRAllTc-99m and patent blueUterineOpenSelective pelvic and para-aortic LND with bilateral biopsies from 3–4 pelvic sites and 1–2 aortic sitesNR
      Darai, 2015 (Senti-ENDO)
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      France125ProspectiveJuly 2007 through August 2009AllMethylene blueCervicalLaparoscopicComplete pelvic LND, paraaortic LND if positive intraoperative histology or after definitive histologyH&E, IHC, ultrastaging
      Delaloye et al, 2007
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      Intraoperative lymphatic mapping and sentinel node biopsy using hysteroscopy in patients with endometrial cancer.
      Switzerland60ProspectiveJuly 2001 through June 2005AllMethylene blue or patent blueUterineOpenComplete pelvic and paraaortic LNDH&E, IHC
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      Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC).
      United States120RetrospectiveApril 2011 through June 2013AllBlue dye or ICGCervicalRoboticSelective pelvic and paraaortic LND (surgeon discretion)H&E, IHC, ultrastaging
      Eitan et al, 2015
      • Eitan R.
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      • Krissi H.
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      Robotic blue-dye sentinel lymph node detection for endometrial cancer—factors predicting successful mapping.
      Israel74NRJanuary 2012 through December 2014AllMethylene blueCervicalRoboticMemorial Sloan Kettering algorithm (LND if failed mapping, surgeon discretion paraaortic LND)NR
      Eriksson et al, 2016
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      Low-volume lymph node metastasis discovered during sentinel lymph node mapping for endometrial carcinoma.
      United States642Retrospective2004–2008 (LND), 2006–2013 (SLN)EndometrioidTc-99mCervicalNRMemorial Sloan Kettering algorithmH&E, IHC, ultrastaging
      Farghali et al, 2015
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      Accuracy of sentinel node in detecting lymph node metastasis in primary endometrial carcinoma.
      Egypt93NRMay 2007 through May 2011AllTc99m sulfide and patent blueUterineOpenSelective pelvic and paraaortic LND by tumor grade, invasion depth, size, location, and patient fitnessH&E, IHC, ultrastaging
      Favero et al, 2015
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      Laparoscopic sentinel lymph node detection after hysteroscopic injection of technetium-99 in patients with endometrial cancer.
      Brazil42ProspectiveJanuary 2008 through December 2012AllTc-99mUterineLaparoscopicComplete pelvic and paraaortic LNDH&E, ultrastaging
      Ferraioli et al, 2015
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      France30RetrospectiveDecember 1998 through May 2012Endometrioid, clear cell, papillary serousTc-99m and isosulfan blueCervicalLaparoscopicPelvic LND and paraaortic by guidelinesH&E, ultrastaging
      Fersis et al, 2004
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      Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.
      Germany10ProspectiveNRAllIsosulfan blueUterineOpenComplete pelvic LND, paraaortic LND when indicatedUltrastaging
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      Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.
      United States18Prospective2002–2004AllIsosulfan blue and ICGUterineOpenComplete pelvic and paraaortic LNDH&E, ultrastaging
      Gien et al, 2005
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      Canada16ProspectiveSeptember 2002 through March 2004AllBlue dyeUterineOpenComplete pelvic LND, paraaortic LND if high-risk histologyNR
      Holloway et al, 2016
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      Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.
      United States119RetrospectiveJuly 2006 through June 2013AllTc-99m and patent blueCervicalRoboticPelvic LND if cancer >1 cm, myometrial invasion >one third, or high-grade histology; paraaortic LND if grade 3 tumor/type 2 histology, any depth of invasion, positive lymph nodes on frozen section, low-grade tumor with middle or outer-third myometrial invasionH&E, IHC, ultrastaging
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      Laparoscopic detection of sentinel lymph nodes using blue dye in women with cervical and endometrial cancer.
      Czech Republic25ProspectiveFebruary 2000 through September 2003AllTc-99m and patent blue or Tc-99m and ICGCervical and uterineLaparoscopicComplete pelvic LND, paraaortic LND if suspicious pelvic lymph nodesNR
      How et al, 2012
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      Canada100ProspectiveDecember 2010 through April 2012AllTc-99m and methylene blueCervicalRoboticComplete pelvic LND, para-aortic LND if type II, grade 2 or 3 endometrioid, carcinosarcoma, positive SLN on intraoperative frozen section, or grossly enlarged pelvic LNsH&E, IHC, ultrastaging
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      Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer.
      Canada100ProspectiveApril 2013 through August 2014AllTc-99m and ICGCervicalRoboticComplete pelvic LND, paraaortic LND if preoperative type II, grade 3 endometrioid, positive SLN on intraoperative frozen section, or grossly enlarged paraaortic LNsH&E, IHC, ultrastaging
      Kadkhodayan et al, 2014
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      Lymphatic mapping and sentinel node biopsy in endometrial cancer—a feasibility study using cervical injection of radiotracer and blue dye.
      Iran24NROctober 2010 through December 2012AllBlue and radiotracerCervicalNRComplete pelvic LND, para-aortic LND if clear cell, serous, or adenosquamous type or grade 2–3 endometrioidH&E
      Kataoka et al, 2016
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      The importance of para-aortic lymph nodes in sentinel lymph node mapping for endometrial cancer by using hysteroscopic radio-isotope tracer injection combined with subserosal dye injection: prospective study.
      Japan55ProspectiveApril 2009 through December 2012AllMethylene blueUterineOpenComplete pelvic LND, para-aortic LND if metastasis to pelvic lymph node, myometrial invasion >50%, grade 3, serous adenocarcinoma, or clear cell adenocarcinomaH&E, IHC, ultrastaging
      Koskas et al, 2013
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      Accuracy of a nomogram for prediction of lymph-node metastasis detected with conventional histopathology and ultrastaging in endometrial cancer.
      France187Prospective2007–2011AllICG or methylene blueNRLaparoscopicComplete pelvic LND, paraaortic LND if type II, metastases on intraoperative histology or after definitive histologyH&E, ultrastaging
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      Turkey26Prospective2010–2011AllTc-99m and patient blueCervical and UterineOpenComplete pelvic LND, paraaortic LND by guidelinesH&E, IHC, ultrastaging
      Laios et al, 2015
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      A prospective pilot study of detection of sentinel lymph nodes in gynaecological cancers using a novel near infrared fluorescence imaging system.
      United Kingdom28ProspectiveOctober 2012 through September 2014AllMethylene blueCervicalLaparoscopicComplete pelvic and paraaortic LNDUltrastaging
      Lelievre et al, 2004
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      Sentinel lymph node biopsy in cervix and corpus uteri cancers.
      France12ProspectiveJanuary 2002 through December 2002AllMethylene blueCervicalLaparoscopicComplete pelvic LND, para-aortic LND if pelvic metastasis on intraoperative frozen SLNH&E, IHC, ultrastaging
      Li et al, 2009
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      China31NRSeptember 2004 through February 2007AllTc-99m and methylene blueUterineOpenComplete pelvic LND, selective paraaortic LNDH&E
      Lopes et al, 2007
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      Sentinel lymph node in endometrial cancer.
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      Lopez-De la Manzanara et al, 2014
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      Sentinel lymph node detection using 99mTc combined with methylene blue cervical injection for endometrial cancer surgical management: a prospective study.
      Spain50ProspectiveSeptember 2011 through December 2013AllTc-99mCervicalLaparoscopicComplete pelvic LND, selective paraaortic LNDH&E, ultrastaging
      Mais et al, 2010
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      Intraoperative sentinel lymph node detection by vital dye through laparoscopy or laparotomy in early endometrial cancer.
      Italy34ProspectiveNRAllTc-99m and patent blueCervicalLaparoscopicComplete pelvic LND, selective paraaortic LNDH&E, IHC, ultrastaging
      Mosgaard et al, 2013
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      Denmark32ProspectiveOctober 2005 through December 2008AdenocarcinomaTc-99m and blue dyeUterineOpenComplete pelvic and paraaortic LNDH&E, IHC, ultrastaging
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      Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.
      Germany31ProspectiveAugust 2008 through April 2012AllTc99m with or without blue dyeUterineLaparoscopicComplete pelvic and paraaortic LNDH&E, IHC, ultrastaging
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      The added value of SPECT/CT in sentinel lymph nodes mapping for endometrial carcinoma.
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      Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer.
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      United States123ProspectiveMarch 2012 through May 2015AllICGCervicalRoboticPelvic and paraaortic LND if serous, clear cell, or carcinosarcoma histology preoperative, tumor size >2 cm, >50% myometrial invasion, grade 3 histology, suspicious nonsentinel pelvic or paraaortic lymph nodes, positive SLN on frozenH&E, ultrastaging
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      Single photon emission computed tomography SPECT-CT improves sentinel node detection and localization in cervical and uterine malignancy.
      United States40ProspectiveNRNRTc-99m and patent blueCervicalOpenComplete pelvic LND, selective paraaortic LNDNR
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      Laparoscopic indocyanine green sentinel lymph node mapping in endometrial cancer.
      Switzerland75ProspectiveDecember 2012 through September 2015AllTc-99mCervicalLaparoscopicPelvic LND unless type I well differentiated <50% myometrial invasion, paraaortic LND if type 2 or type 1 poorly differentiated, or >50% invasionH&E, IHC, ultrastaging
      Pelosi et al, 2003
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      Pre-operative lymphatic mapping and intra-operative sentinel lymph node detection in early stage endometrial cancer.
      Italy16NRFebruary 2001 through April 2002AdenocarcinomaTc-99mCervicalLaparoscopicComplete pelvic LND, selective paraaortic LNDH&E, IHC, ultrastaging
      Perrone et al, 2008
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      Cervical and hysteroscopic injection for identification of sentinel lymph node in endometrial cancer.
      Italy40ProspectiveJanuary 2001 through March 2007AllTc-99m and blue dyeCervicalLaparoscopicComplete pelvic LND, paraaortic LND in high-grade EC or suspicious SLNH&E, IHC, ultrastaging
      Raimond et al, 2014
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      Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: results of a retrospective multicenter study.
      France156RetrospectiveJanu 2000 through December 2012Endometrioid, adenocarcinoma, adenosquamousTc-99mCervicalOpenComplete pelvic LND, selective paraaortic LNDH&E, IHC, ultrastaging
      Raspagliesi et al, 2004
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      Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study.
      Italy18ProspectiveNRAdenocarcinomaICGUterineOpenPelvic LND if myometrial invasion >50% or grade 3 tumor, paraaortic LND if serous papillary or clear cellH&E, ultrastaging
      Robova et al, 2009
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      Lymphatic mapping in endometrial cancer: comparison of hysteroscopic and subserosal injection and the distribution of sentinel lymph nodes.
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      Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection.
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      Sentinel Lymph Node Biopsy in Endometrial Cancer–Comparison of 2 Detection Methods.
      Poland188ProspectiveFebruary 2011 through August 2014AllTc-99mCervical and uterineOpenPelvic and paraaortic LND if grade 3, >50% myometrial invasion or cervical involvement; not if morbid obesity, advanced age, or poor general statusH&E
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      CT, computed tomography; EC, endometrial cancer; H&E, hematoxylin and eosin; ICG, indocyanine green; IHC, immunohistochemistry; LND, lymphadenectomy; MRI, magnetic resonance imaging; NR, not reported; PET, positron emission tomography; SLN, sentinel lymph node; Tc-99m, technecium-99.
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      The mean age of the patients was 62 years (95% confidence interval [CI], 61–64) (49 studies), and mean BMI was 30 kg/m2 (95% CI, 29–31) (35 studies). Forty-two percent of SLN cases were performed by laparotomy (95% CI, 28–56), 41% by laparoscopy (95% CI, 27–54), and 17% with robotic assistance (95% CI, 7–28). Forty-four percent of SLN cases used dye alone to detect SLNs (95% CI, 30–57), 44% used a dye and a radiotracer (95% CI, 30–57), and 12% used a radiotracer alone (95% CI, 4–22). When dye was utilized, a blue dye was used more frequently than indocyanine green (88% vs 12%), and patent blue was the most common blue dye used. Most studies used cervical injection techniques for dye and/or radiotracer distribution (58%, 95% CI, 44–71), 9% used cervical and uterine injection (95% CI, 1–17), and 33% used uterine injection alone (95% CI, 23–51).

      SLN detection rates

      The SLN detection rate ranged from 23% to 100%, with a pooled average of 81% (95% CI, 77–84, 53 studies) (Figure 2). The bilateral detection rate ranged from 6% to 88%, with a pooled average of 50% (95% CI, 44–56, 36 studies) (Figure 3). The side-specific detection rate ranged from 25% to 92%, with a pooled average of 66% (95% CI, 62–70, 36 studies). The paraaortic detection rate ranged from 0% to 84%, with a pooled average of 17% (95% CI, 11–23, 41 studies) (Figure 4). The mean number of SLNs detected per mapped patient was 2.9 (95% CI, 2.5–3.3, range, 1–8, 49 studies).
      Figure thumbnail gr2
      Figure 2Overall SLN detection rate
      CI, confidence interval; SLN, sentinel lymph node.
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      Figure thumbnail gr3
      Figure 3Bilateral SLN detection rate
      CI, confidence interval; SLN, sentinel lymph node.
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      Figure thumbnail gr4
      Figure 4Paraaortic SLN detection rate
      CI, confidence interval; SLN, sentinel lymph node.
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.

      Factors associated with SLN detection rates

      Nonendometrioid histology (eg, serous, carcinosarcoma, and clear cell) was not associated with any significant differences in SLN detection compared with endometrioid histology (P = .515) (Table 3). Additionally, study size, average patient BMI ≥30 kg/m2, tumor grade, and surgical approach were not significantly associated with detection rates. Cervical injection was associated with significantly higher rates of bilateral SLN detection (56% vs 33%, P = .003) compared with uterine injection. However, cervical injection was associated with a significantly lower rate of paraaortic SLN detection than uterine injection (7% vs 27%, P = .001). Use of indocyanine green was associated with higher rates of bilateral SLN detection (75% vs 51%, P = .008) than blue dye. Preoperative lymphoscintigraphy and combined use of a radiotracer and dye were associated with higher rates of overall SLN detection (86% vs 76%, P = .016, and 87% vs 78%, P = .008, respectively) but showed no significant difference in rates of bilateral or paraaortic SLN detection.
      Table 3Univariate meta-regression of SLN detection rate and study characteristics
      VariablesStudies, nOverall detection, % (95% CI)P valueBilateral detection, % (95% CI)P valuePara-aortic detection, % (95% CI)P value
      Study characteristics
       Study size
      ≥ 30 patients5383.2 (79.8–86.6).10141.5 (25.7–57.2).14816.0 (9.2–22.7).710
      <30 patients75.4 (66.1–84.7)52.8 (45.9–59.6)18.7 (4.90–32.6)
      Patient and tumor characteristics
       Patient BMI
      Average BMI ≥30 kg/m23582.2 (75.6–88.9).72849.2 (38.7–59.7).43716.5 (7.1–26.0).863
      Average BMI <30 kg/m284.3 (80.2–88.5)55.8 (45.1–66.5)17.8 (9.5–26.1)
       Tumor grade
      Grade 15
      Includes 3 studies comparing ICG and blue dye,12,22,28 2 comparing radiotracer with/without dye,57,67 3 comparing cervical vs uterine injection,41,49,76 5 comparing grade 1 vs grades 2–3,22,27,29,37,64 and 5 comparing endometrioid and non-endometrioid histology.22,27,29,37,64
      78.4 (61.7–95.0).941N/ANRN/ANR
      Grade II–III77.6 (64.7–90.4)N/AN/A
      Tumor histology
      Endometrioid7
      Includes 3 studies comparing ICG and blue dye,12,22,28 2 comparing radiotracer with/without dye,57,67 3 comparing cervical vs uterine injection,41,49,76 5 comparing grade 1 vs grades 2–3,22,27,29,37,64 and 5 comparing endometrioid and non-endometrioid histology.22,27,29,37,64
      81.6 (72.9–90.2).598N/ANRN/ANR
      Nonendometrioid75.8 (59.3–92.4)N/AN/A
      SLN technique characteristics
       Surgical approach
      Robotic5085.6 (79.0–92.2).26646.2 (39.2–53.1).13312.8 (4.0–21.6).616
      Laparotomy, laparoscopy79.0 (75.2–82.9)58.2 (44.6–71.7)17.9 (10.8–25.0)
       Preoperative lymphoscintigraphy
      Yes5386.6 (83.1–90.2)0.01651.4 (42.6–60.1)0.60314.1 (8.1–20.2)0.408
      No76.2 (71.0–81.3)47.7 (39.4–56.0)19.7 (9.2–30.3)
       Injection site
      Cervical52
      Includes 3 studies comparing ICG and blue dye,12,22,28 2 comparing radiotracer with/without dye,57,67 3 comparing cervical vs uterine injection,41,49,76 5 comparing grade 1 vs grades 2–3,22,27,29,37,64 and 5 comparing endometrioid and non-endometrioid histology.22,27,29,37,64
      80.2 (75.7–84.8).62255.5 (48.7–62.3).0036.7 (3.4–10.1).001
      Uterine77.6 (71.2–84.1)33.0 (24.2–41.9)26.8 (15.3–38.2)
       Radiotracer used
      Yes53
      Includes 3 studies comparing ICG and blue dye,12,22,28 2 comparing radiotracer with/without dye,57,67 3 comparing cervical vs uterine injection,41,49,76 5 comparing grade 1 vs grades 2–3,22,27,29,37,64 and 5 comparing endometrioid and non-endometrioid histology.22,27,29,37,64
      84.9 (81.5–88.4).10148.0 (40.4–55.6).16514.9 (8.3–21.4).458
      No78.3 (73.4–83.1)57.2 (48.6–65.8)10.5 (4.1–16.9)
       Dye and radiotracer used
      Yes53
      Includes 3 studies comparing ICG and blue dye,12,22,28 2 comparing radiotracer with/without dye,57,67 3 comparing cervical vs uterine injection,41,49,76 5 comparing grade 1 vs grades 2–3,22,27,29,37,64 and 5 comparing endometrioid and non-endometrioid histology.22,27,29,37,64
      87.7 (84.4–90.9).01551.2 (43.9–58.5).74811.6 (4.7–18.5).674
      No77.7 (73.3–82.1)53.2 (44.8–61.6)14.0 (7.5–20.5)
       Dye tracer
      Indocyanine green53
      Includes 3 studies comparing ICG and blue dye,12,22,28 2 comparing radiotracer with/without dye,57,67 3 comparing cervical vs uterine injection,41,49,76 5 comparing grade 1 vs grades 2–3,22,27,29,37,64 and 5 comparing endometrioid and non-endometrioid histology.22,27,29,37,64
      90.3 (84.8–95.0).12574.6 (65.9–83.3).00813.5 (0–29.5).771
      Blue dye81.0 (77.8–84.3)50.5 (45.5–55.5)10.7 (5.7–15.7)
      Intraoperative frozen section42
      Yes90.4 (86.8–94.0).02963.6 (52.9–74.4).0309.4 (2.2–16.6).292
      No78.3 (73.8–82.8)45.4 (37.9–53.0)16.3 (8.4–24.2)
      Average refers to mean or median, whichever was reported in the study.
      BMI, body mass index; CI, confidence interval; N/A, not applicable (eg, only 1 study reporting detection rates comparing subgroup characteristics); NR, not reported; SLN, sentinel lymph node.
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      a Includes 3 studies comparing ICG and blue dye,
      • Tanner E.J.
      • Sinno A.K.
      • Stone R.L.
      • Levinson K.L.
      • Long K.C.
      • Fader A.N.
      Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer.
      • Buda A.
      • Crivellaro C.
      • Elisei F.
      • et al.
      Impact of indocyanine green for sentinel lymph node mapping in early stage endometrial and cervical cancer: comparison with conventional radiotracer Tc and/or blue dye.
      • St Clair C.M.
      • Eriksson A.G.Z.
      • Ducie J.A.
      • et al.
      Low-volume lymph node metastasis discovered during sentinel lymph node mapping for endometrial carcinoma.
      2 comparing radiotracer with/without dye,
      • Sawicki S.
      • Lass P.
      • Wydra D.
      Sentinel Lymph Node Biopsy in Endometrial Cancer–Comparison of 2 Detection Methods.
      • Kataoka F.
      • Susumu N.
      • Yamagami W.
      • et al.
      The importance of para-aortic lymph nodes in sentinel lymph node mapping for endometrial cancer by using hysteroscopic radio-isotope tracer injection combined with subserosal dye injection: prospective study.
      3 comparing cervical vs uterine injection,
      • Kuru O.
      • Topuz S.
      • Sen S.
      • Iyibozkurt C.
      • Berkman S.
      Sentinel lymph node biopsy in endometrial cancer: description of the technique and preliminary results.
      • Niikura H.
      • Kaiho-Sakuma M.
      • Tokunaga H.
      • et al.
      Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer.
      • Rossi E.C.
      • Jackson A.
      • Ivanova A.
      • Boggess J.F.
      Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection.
      5 comparing grade 1 vs grades 2–3,
      • Buda A.
      • Crivellaro C.
      • Elisei F.
      • et al.
      Impact of indocyanine green for sentinel lymph node mapping in early stage endometrial and cervical cancer: comparison with conventional radiotracer Tc and/or blue dye.
      • Eitan R.
      • Sabah G.
      • Krissi H.
      • et al.
      Robotic blue-dye sentinel lymph node detection for endometrial cancer—factors predicting successful mapping.
      • Farghali M.M.
      • Allam I.S.
      • Abdelazim I.A.
      • et al.
      Accuracy of sentinel node in detecting lymph node metastasis in primary endometrial carcinoma.
      • How J.
      • Lau S.
      • Press J.
      • et al.
      Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study.
      • Naaman Y.
      • Pinkas L.
      • Roitman S.
      • et al.
      The added value of SPECT/CT in sentinel lymph nodes mapping for endometrial carcinoma.
      and 5 comparing endometrioid and non-endometrioid histology.
      • Buda A.
      • Crivellaro C.
      • Elisei F.
      • et al.
      Impact of indocyanine green for sentinel lymph node mapping in early stage endometrial and cervical cancer: comparison with conventional radiotracer Tc and/or blue dye.
      • Eitan R.
      • Sabah G.
      • Krissi H.
      • et al.
      Robotic blue-dye sentinel lymph node detection for endometrial cancer—factors predicting successful mapping.
      • Farghali M.M.
      • Allam I.S.
      • Abdelazim I.A.
      • et al.
      Accuracy of sentinel node in detecting lymph node metastasis in primary endometrial carcinoma.
      • How J.
      • Lau S.
      • Press J.
      • et al.
      Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study.
      • Naaman Y.
      • Pinkas L.
      • Roitman S.
      • et al.
      The added value of SPECT/CT in sentinel lymph nodes mapping for endometrial carcinoma.

      SLN diagnostic accuracy

      The pooled sensitivity of sentinel lymph node detection of metastatic disease was 96% (95% CI, 93–98, 47 studies) (Figure 5). The pooled negative predictive value was 99.7%. In cases with SLN metastases, SLNs were the only positive nodes identified 66% of the time (22 studies).
      Figure thumbnail gr5
      Figure 5Sensitivity of SLN detection
      CI, confidence interval; SLN, sentinel lymph node.
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      In cases with positive SLNs, these were macrometastases in 29%, micrometastases in 39%, and isolated tumor cells in 32% of cases (14 studies). There was no significant difference in the sensitivity of SLN detection of metastases by study size, preoperative lymphoscintigraphy, injection site, radiotracer and/or dye used, intraoperative frozen section, or use of ultrastaging (Appendix Table 2).

      Operating time and adverse events

      The additional operating time for SLN mapping compared with LND ranged from 3 to 40 minutes (6 studies).
      • Burke T.W.
      • Levenback C.
      • Tornos C.
      • Morris M.
      • Wharton J.T.
      • Gershenson D.M.
      Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high- risk endometrial cancer: results of a pilot study.
      • St Clair C.M.
      • Eriksson A.G.Z.
      • Ducie J.A.
      • et al.
      Low-volume lymph node metastasis discovered during sentinel lymph node mapping for endometrial carcinoma.
      • Holloway R.W.
      • Gupta S.
      • Stavitzski N.M.
      • et al.
      Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.
      • Lelievre L.
      • Camatte S.
      • Le Frere-belda M.A.
      • et al.
      Sentinel lymph node biopsy in cervix and corpus uteri cancers.
      • Li B.
      • Wu L.
      • Li X.
      • et al.
      Sentinel lymph node identification in endometrial cancer.
      • Raspagliesi F.
      • Ditto A.
      • Kusamura S.
      • et al.
      Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study.
      One study reported lower blood loss with SLN mapping compared with LND.
      • Papadia A.
      • Imboden S.
      • Siegenthaler F.
      • et al.
      Laparoscopic indocyanine green sentinel lymph node mapping in endometrial cancer.
      In the 24 studies reporting on adverse events (n = 1390 women), 1 patient had an anaphylactic reaction to the blue dye
      • Gien L.T.
      • Kwon J.S.
      • Carey M.S.
      Sentinel node mapping with isosulfan blue dye in endometrial cancer.
      ; no other serious adverse events related to SLN mapping were reported.
      • Torné A.
      • Pahisa J.
      • Vidal-Sicart S.
      • et al.
      Transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR): a new method for sentinel lymph node detection in endometrial cancer.
      • Bats A.-S.
      • Clement D.
      • Larousserie F.
      • et al.
      Does sentinel node biopsy improve the management of endometrial cancer? Data from 43 patients.
      • Daraï E.
      • Dubernard G.
      • Bats A.-S.
      • et al.
      Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study.
      • Desai P.H.
      • Hughes P.
      • Tobias D.H.
      • et al.
      Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC).
      • Farghali M.M.
      • Allam I.S.
      • Abdelazim I.A.
      • et al.
      Accuracy of sentinel node in detecting lymph node metastasis in primary endometrial carcinoma.
      • Favero G.
      • Pfiffer T.
      • Ribeiro A.
      • et al.
      Laparoscopic sentinel lymph node detection after hysteroscopic injection of technetium-99 in patients with endometrial cancer.
      • Frumovitz M.
      • Bodurka D.C.
      • Broaddus R.R.
      • et al.
      Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.
      • Gien L.T.
      • Kwon J.S.
      • Carey M.S.
      Sentinel node mapping with isosulfan blue dye in endometrial cancer.
      • Holub Z.
      • Jabor A.
      • Lukac J.
      • Kliment L.
      Laparoscopic detection of sentinel lymph nodes using blue dye in women with cervical and endometrial cancer.
      • How J.
      • Lau S.
      • Press J.
      • et al.
      Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study.
      • How J.
      • Gotlieb W.H.
      • Press J.Z.
      • et al.
      Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer.
      • Kuru O.
      • Topuz S.
      • Sen S.
      • Iyibozkurt C.
      • Berkman S.
      Sentinel lymph node biopsy in endometrial cancer: description of the technique and preliminary results.
      • Li B.
      • Wu L.
      • Li X.
      • et al.
      Sentinel lymph node identification in endometrial cancer.
      • Lopez-De la Manzanara Cano C.
      • Cordero Garcia J.M.
      • et al.
      Sentinel lymph node detection using 99mTc combined with methylene blue cervical injection for endometrial cancer surgical management: a prospective study.
      • Mucke J.
      • Klapdor R.
      • Schneider M.
      • et al.
      Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.
      • Paley P.J.
      • Veljovich D.S.
      • Press J.Z.
      • Isacson C.
      • Pizer E.
      • Shah C.
      A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging.
      • Papadia A.
      • Imboden S.
      • Siegenthaler F.
      • et al.
      Laparoscopic indocyanine green sentinel lymph node mapping in endometrial cancer.
      • Mosgaard B.J.
      • Skovlund V.R.
      • Hendel H.W.
      Promising results using sentinel node biopsy as a substitute for radical lymphadenectomy in endometrial cancer staging.
      • Raspagliesi F.
      • Ditto A.
      • Kusamura S.
      • et al.
      Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study.
      • Solima E.
      • Martinelli F.
      • Ditto A.
      • et al.
      Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer.
      • Naaman Y.
      • Pinkas L.
      • Roitman S.
      • et al.
      The added value of SPECT/CT in sentinel lymph nodes mapping for endometrial carcinoma.
      • Li B.
      • Li X.
      • Wu L.
      • et al.
      A pilot study of sentinel lymph nodes identification in patients with endometrial cancer.
      • Kataoka F.
      • Susumu N.
      • Yamagami W.
      • et al.
      The importance of para-aortic lymph nodes in sentinel lymph node mapping for endometrial cancer by using hysteroscopic radio-isotope tracer injection combined with subserosal dye injection: prospective study.
      • Perrone A.M.
      • Casadio P.
      • Formelli G.
      • et al.
      Cervical and hysteroscopic injection for identification of sentinel lymph node in endometrial cancer.
      Seven patients experienced serious complications related to completion LND after SLN mapping (5 lymphoceles, 2 vascular injuries).
      • Favero G.
      • Pfiffer T.
      • Ribeiro A.
      • et al.
      Laparoscopic sentinel lymph node detection after hysteroscopic injection of technetium-99 in patients with endometrial cancer.
      • Ferraioli D.
      • Chopin N.
      • Beurrier F.
      • Carrabin N.
      • Buenerd A.
      • Mathevet P.
      The incidence and clinical significance of the micrometastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.
      • Fersis N.
      • Gruber I.
      • Relakis K.
      • et al.
      Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.
      • Frumovitz M.
      • Bodurka D.C.
      • Broaddus R.R.
      • et al.
      Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.
      • Gien L.T.
      • Kwon J.S.
      • Carey M.S.
      Sentinel node mapping with isosulfan blue dye in endometrial cancer.
      • Holloway R.W.
      • Gupta S.
      • Stavitzski N.M.
      • et al.
      Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.
      • Holub Z.
      • Jabor A.
      • Lukac J.
      • Kliment L.
      Laparoscopic detection of sentinel lymph nodes using blue dye in women with cervical and endometrial cancer.
      • Paley P.J.
      • Veljovich D.S.
      • Press J.Z.
      • Isacson C.
      • Pizer E.
      • Shah C.
      A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging.
      • Raspagliesi F.
      • Ditto A.
      • Kusamura S.
      • et al.
      Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study.
      • Robova H.
      • Charvat M.
      • Strnad P.
      • et al.
      Lymphatic mapping in endometrial cancer: comparison of hysteroscopic and subserosal injection and the distribution of sentinel lymph nodes.
      • Sawicki S.
      • Lass P.
      • Wydra D.
      Sentinel Lymph Node Biopsy in Endometrial Cancer–Comparison of 2 Detection Methods.
      • Schiavone M.B.
      • Zivanovic O.
      • Zhou Q.
      • et al.
      Survival in patients with uterine carcinosarcoma undergoing sentinel lymph node mapping.
      • Solima E.
      • Martinelli F.
      • Ditto A.
      • et al.
      Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer.
      None of the studies reporting adverse events reported long-term outcomes comparing the risk of lymphedema in patients undergoing either SLN mapping alone or in comparison with complete lymphadenectomy.

      Association of SLN mapping with treatment and survival

      Four of the 5 studies comparing SLN mapping with standard of care (ie, pelvic and aortic lymphadenectomy by regional endometrial cancer guidelines) found that SLN mapping increased the use of adjuvant therapy (Table 4).
      • Daraï E.
      • Dubernard G.
      • Bats A.-S.
      • et al.
      Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study.
      • Holloway R.W.
      • Gupta S.
      • Stavitzski N.M.
      • et al.
      Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.
      • Eriksson A.G.Z.
      • Ducie J.
      • Ali N.
      • et al.
      Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.
      • Raimond E.
      • Ballester M.
      • Hudry D.
      • et al.
      Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: results of a retrospective multicenter study.
      • Schiavone M.B.
      • Zivanovic O.
      • Zhou Q.
      • et al.
      Survival of patients with uterine carcinosarcoma undergoing sentinel lymph node mapping.
      The sole study in which adjuvant therapy use did not increase with the performance of SLN mapping was in patients with uterine carcinosarcoma.
      Table 4Associations between SLN mapping, endometrial cancer treatment, and survival
      StudyStudy sizeSLN reference standardComparison groupFollow-up time (range)TreatmentRecurrence-free survival
      Darai, 2015
      • Morice P.
      • Leary A.
      • Creutzberg C.
      • Abu-Rustum N.
      • Darai E.
      Endometrial cancer.
      125Complete pelvic LND, paraaortic LND if positive intraoperative histology or after definitive histologyNone50 (5–77 mo)Chemotherapy more frequent with positive SLN (50% vs 12.5%, P = .009)84.7% No difference with or without SLN detection
      Eriksson et al, 2016
      • Eriksson A.G.Z.
      • Ducie J.
      • Ali N.
      • et al.
      Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.
      642 (SLN), 493 (LND)Memorial Sloan Kettering algorithm (LND if failed mapping, surgeon discretion paraaortic LND)Complete pelvic and paraaortic LND36 moAdjuvant therapy more frequent in SLN cohort (27.1% vs 10.8%, P < .001)94.9% (SLN), 96.8% (LND) No difference
      Ferraioli et al, 2014
      • Ferraioli D.
      • Chopin N.
      • Beurrier F.
      • Carrabin N.
      • Mathevet P.
      The incidence and clinical significance of the micro-metastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.
      10 (relapse), 20 (controls)Pelvic LND and paraaortic by guidelinesEndometrial cancer after SLN mapping and LND without recurrence matched on age, FIGO stage, and histopathology21.9 (8–45 mo)No difference in recurrence with or without SLN detection
      Frumovitz et al, 2007
      • Frumovitz M.
      • Bodurka D.C.
      • Broaddus R.R.
      • et al.
      Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.
      18Complete pelvic and paraaortic LNDNone32.4 (1–45 months)Failed SLN detection in 3/3 patients with recurrence
      Holloway et al, 2016
      • Holloway R.W.
      • Gupta S.
      • Stavitzski N.M.
      • et al.
      Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.
      119 (SLN), 661 (LND)Pelvic LND if cancer >1 cm, myometrial invasion >one third, or high-grade histology; paraaortic LND if grade 3 tumor/type 2 histology, any depth of invasion, positive lymph nodes on frozen section, low-grade tumor with middle or outer-third myometrial invasionNon–SLN-mapped patients with same criteria for pelvic and/or paraaortic LNDAdjuvant chemotherapy and radiation more frequent in SLN cohort (28.6% vs 16.3%, P < .003)
      Pelosi et al, 2003
      • Pelosi E.
      • Arena V.
      • Baudino B.
      • et al.
      Pre-operative lymphatic mapping and intra-operative sentinel lymph node detection in early stage endometrial cancer.
      16Complete pelvic LND, selective paraaortic LND16.7 (4–22 mo)No recurrence
      Raimond et al, 2014
      • Raimond E.
      • Ballester M.
      • Hudry D.
      • et al.
      Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: results of a retrospective multicenter study.
      156 (SLN), 115 (LND)Complete pelvic LND, selective paraaortic LNDComplete pelvic LND, selective paraaortic LND60 moAdjuvant therapy more frequent in SLN cohort (22% vs 13%, P < .001)88.4% (SLN), 84.2% (LND) No difference in mean time to recurrence (16.6 vs 17 mo)
      Schiavone et al, 2016
      • Schiavone M.B.
      • Zivanovic O.
      • Zhou Q.
      • et al.
      Survival of patients with uterine carcinosarcoma undergoing sentinel lymph node mapping.
      48 (SLN), 88 (LND)Memorial Sloan Kettering algorithm (LND if failed mapping, surgeon discretion paraaortic LND)Complete pelvic and paraaortic LND16.2 (1–77 mo, SLN), 62 (3–176, LND)No difference in adjuvant therapy (92% vs 90%, P = .15)3 year progression-free survival: 23 mo (SLN), 23.2 (LND)
      FIGO, International Federation of Gynecology and Obstetrics; LND, lymphadenectomy; SLN, sentinel lymph node.
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      Three of 3 studies with a median follow-up of 17–50 months found no difference in the progression-free survival between patients with successful and failed SLN mapping.
      • Eriksson A.G.Z.
      • Ducie J.
      • Ali N.
      • et al.
      Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.
      • Raimond E.
      • Ballester M.
      • Hudry D.
      • et al.
      Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: results of a retrospective multicenter study.
      • Schiavone M.B.
      • Zivanovic O.
      • Zhou Q.
      • et al.
      Survival of patients with uterine carcinosarcoma undergoing sentinel lymph node mapping.
      Three of 3 studies with a median follow-up of 16–32 months found no difference in the progression-free survival for patients who underwent SLN mapping compared with patients who underwent primary LND.
      • Daraï E.
      • Dubernard G.
      • Bats A.-S.
      • et al.
      Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study.
      • Frumovitz M.
      • Bodurka D.C.
      • Broaddus R.R.
      • et al.
      Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.
      • Pelosi E.
      • Arena V.
      • Baudino B.
      • et al.
      Pre-operative lymphatic mapping and intra-operative sentinel lymph node detection in early stage endometrial cancer.
      • Ferraioli D.
      • Chopin N.
      • Beurrier F.
      • Carrabin N.
      • Mathevet P.
      The incidence and clinical significance of the micro-metastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.

      Comment

      In this systematic review and meta-analysis of 55 studies including 4915 women investigating the utility of SLN mapping for endometrial cancer, the following 3 primary findings emerged: (1) the pooled overall SLN detection rates were relatively high at 81% (95% CI, 77–84) with 51% (95% CI, 45–54) bilateral nodal detection; (2) the pooled sensitivity of SLN mapping for the detection of lymphatic metastases was high at 96% (95% CI, 92–98); (3) and the use of cervical injection with combination blue dye and radiotracer or indocyanine green dye alone increased the overall SLN detection rate.
      Notably, we identified a higher pooled detection rate and a higher pooled sensitivity for the detection of lymphatic metastases than in prior meta-analyses.
      • Kang S.
      • Yoo H.J.
      • Hwang J.H.
      • Lim M.-C.
      • Seo S.-S.
      • Park S.-Y.
      Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies.
      • Ansari M.
      • Rad M.A.G.
      • Hassanzadeh M.
      • et al.
      Sentinel node biopsy in endometrial cancer: systematic review and meta-analysis of the literature.
      • Selman T.J.
      • Mann C.H.
      • Zamora J.
      • Khan K.S.
      A systematic review of tests for lymph node status in primary endometrial cancer.
      Our analysis suggests that the SLN detection rate and sensitivity in endometrial cancer approaches those observed in breast cancer and melanoma, malignancies in which SLN mapping is the standard of care.
      • Mansel R.E.
      • Fallowfield L.
      • Kissin M.
      • et al.
      Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.
      These improvements may reflect gynecological surgeons’ growing experience with SLN mapping and increased utilization of more innovative dye and detection techniques.
      Additionally, these data provide the rationale to consider SLN mapping as an alternative standard of care in select women with apparent early-stage endometrial cancer, especially when SLN mapping is performed by experienced, high-volume endometrial cancer surgeons.
      SLN mapping with indocyanine green demonstrated high rates of bilateral mapping.
      • Ruscito I.
      • Gasparri M.L.
      • Braicu E.I.
      • et al.
      Sentinel node mapping in cervical and endometrial cancer: indocyanine green versus other conventional dyes—a meta-analysis.
      • Xiong L.
      • Gazyakan E.
      • Yang W.
      • et al.
      Indocyanine green fluorescence-guided sentinel node biopsy: a meta-analysis on detection rate and diagnostic performance.
      Given that other dye types and the combination of dye and radiotracer demonstrated high overall SLN detection rates but did not significantly improve bilateral mapping rates, indocyanine green could be considered as the preferred mapping agent for SLN mapping of endometrial cancer.
      Additionally, the use of indocyanine green has several advantages compared with radiocolloids, including less pain with injection, lower cost, fewer adverse effects, and quick transcutaneous real-time visualization.
      • Zhang X.
      • Li Y.
      • Zhou Y.
      • et al.
      Diagnostic performance of indocyanine green-guided sentinel lymph node biopsy in breast cancer: a meta-analysis.
      • Ruscito I.
      • Gasparri M.L.
      • Braicu E.I.
      • et al.
      Sentinel node mapping in cervical and endometrial cancer: indocyanine green versus other conventional dyes—a meta-analysis.
      Preoperative lymphoscintigraphy did not significantly increase bilateral or paraaortic detection rates, but there were a variety of methods (eg, different radiotracers and imaging modalities) and time delays used. Further research is needed to explore the possible benefits of preoperative lymphoscintigraphy in surgical planning for endometrial cancer, especially given the potential costs of this technique.
      Cervical injection increased bilateral SLN detection rates, but we did not observe that cervical injection increases paraaortic detection as suggested in a prior review.
      • Cormier B.
      • Rozenholc A.T.
      • Gotlieb W.
      • Plante M.
      • Giede C.
      Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research.
      This, however, may not have a substantial impact on patient outcomes. Whereas paraaortic metastases are a poor prognostic indicator, the incidence of paraaortic metastases in the absence of pelvic metastases is exceedingly low (1–5%), especially in women with low-grade endometrial cancer. If paraaortic SLN mapping fails, pelvic SLN mapping is likely sufficient in most patients, given the low likelihood of isolated paraaortic metastases in this setting.
      Interestingly, we did not identify a significant difference in sensitivity of SLN mapping with ultrastaging, despite the large number of studies (n = 44) utilizing this nodal evaluation technique. This may reflect the limited experience and lack of uniform ultrastaging guidelines in endometrial cancer. Alternatively, the studies included in our meta-analysis may not be powered to ascertain the impact of ultrastaging of SLNs. Because ultrastaging is a costly and time-consuming lymphatic assessment strategy, further research is needed regarding the value of this approach and the impact of the micrometastases and isolated tumor cells identified through ultrastaging on endometrial cancer prognosis.
      • Maaskant-Braat A.J.
      • van de Poll-Franse L.V.
      • Voogd A.C.
      • et al.
      Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study.
      The controversy surrounding the value of ultrastaging in endometrial cancer reflects the broader uncertainty regarding the value of lymphatic assessment in endometrial cancer. Although prospective randomized trial data demonstrate the limited impact of lymphadenectomy on survival, retrospective data suggest a therapeutic benefit of lymphadenectomy in high-risk patients.
      • Frost J.A.
      • Webster K.E.
      • Bryant A.
      • Morrison J.
      Lymphadenectomy for the management of endometrial cancer.
      • Todo Y.
      • Kato H.
      • Kaneuchi M.
      • Watari H.
      • Takeda M.
      • Sakuragi N.
      Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis.
      As such, the true value of SLN mapping may be to allow the tailoring of adjuvant therapy for high-risk patients while also minimizing the risk of harm that occurs with full lymphadenectomy.
      Given remaining uncertainties, the assessment of lymph nodes continues to be an important aspect of surgical staging in select women with endometrial cancer and is recognized by the National Comprehensive Cancer Network as a procedure that provides important prognostic information that may alter adjuvant treatment decisions.

      Fayna Ferkle N, Nicole McMillian P, Jillian Scavone M, et al. NCCN guidelines index uterine neoplasms TOC discussion NCCN guidelines, version 2. 2016 panel members uterine neoplasms MD/liaison, Dana-Farber/Brigham and Women’s Cancer Center. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed May 30, 2016.

      Our data showed that SLN mapping led to upstaging of a number of women and helped tailor the subsequent receipt of additional therapy, such as chemotherapy and/or radiation, known to improve survival.
      • Todo Y.
      • Kato H.
      • Kaneuchi M.
      • Watari H.
      • Takeda M.
      • Sakuragi N.
      Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis.
      We were underpowered to detect any differences in survival associated with SLN vs other strategies of lymph node assessment.

      Strengths and limitations

      Our systematic review and meta-analysis has limitations. We excluded non-English studies. We did not have individual patient data with which to analyze the impact of BMI, which may have biased BMI results toward the null. We found evidence of a significant small-study effect within our meta-analyses and in publication bias (data available on request). Nonetheless, although there was substantial variation between studies, this heterogeneity was largely explained by the SLN mapping variables that were included and controlled for in our meta-regressions.
      Finally, an area of great interest that is notably absent from the reviewed literature is the lymphedema risk in women with endometrial cancer who undergo SLN mapping. Lymphedema rates after complete pelvic and aortic LND may be as high as 20% in this setting.
      One of the potential advantages of SLN mapping is the reduced disruption of lymphatic channels compared with more comprehensive lymphadenectomy. In the breast cancer literature, replacing axillary lymphadenectomy with SLN mapping resulted in a two thirds reduction in the risk of lymphedema in the affected extremity.
      • Mansel R.E.
      • Fallowfield L.
      • Kissin M.
      • et al.
      Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.
      Future studies on SLN mapping in endometrial cancer should consider assessment of lymphedema in the postoperative and surveillance periods. We await the results of a prospective trial evaluating the baseline lymphedema risk with lymphadenectomy in endometrial cancer (https://clinicaltrials.gov/ct2/show/NCT00956670).

      Conclusions and implications

      In this contemporary systematic review and meta-analysis of 55 studies, sentinel lymph node mapping successfully identified nodal metastases in the vast majority of the women with endometrial cancer, with high sensitivity for the detection of lymphatic metastases. Cervical injection techniques and the use of indocyanine green dye likely increase bilateral sentinel node detection rates. Sentinel lymph node mapping is emerging as an alternative standard of care in the staging and management of select women with endometrial cancer.

      Appendix

      Appendix Table 1Quality assessment of included studies
      Author, yearPatient selectionIndex testReference standardFlow and timing
      Was a consecutive or random sample of patients enrolledWas a case–control design avoided? Did the study avoid inappropriate exclusions?Were the index test results interpreted without knowledge of the results of the reference standard?If a threshold was used, was it prespecified?Reference standardIs the reference standard likely to correctly classify the target condition?Were the reference standard results interpreted without knowledge of the results of the index test?Was there an appropriate interval between the index test and reference standard?Did all patients receive the same reference standard?Were all patients included in the analysis?
      Allameh et al, 2015
      • Allameh T.
      • Hashemi V.
      • Mohammadizadeh F.
      • Behnamfar F.
      Sentinel lymph node mapping in early stage of endometrial and cervical cancers.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Altgassen et al, 2007
      • Altgassen C.
      • Pagenstecher J.
      • Hornung D.
      • Diedrich K.
      • Hornemann A.
      A new approach to label sentinel nodes in endometrial cancer.
      YYNNRComplete pelvic lymphadenectomyYNNRYY
      Ballester 2013
      • Ballester M.
      • Naoura I.
      • Chereau E.
      • et al.
      Sentinel node biopsy upstages patients with presumed low- and intermediate-risk endometrial cancer: results of a multicenter study.
      NRYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Basta et al, 2005
      • Basta A.
      • Pityński K.
      • Basta P.
      • Hubaiewska-Hoła A.
      • Opławski M.
      • Przeszlakowski D.
      Sentinel node in gynaecological oncology.
      NRYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Bats et al, 2008
      • Bats A.-S.
      • Clement D.
      • Larousserie F.
      • et al.
      Does sentinel node biopsy improve the management of endometrial cancer? Data from 43 patients.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Buda et al, 2016
      • Buda A.
      • Crivellaro C.
      • Elisei F.
      • et al.
      Impact of indocyanine green for sentinel lymph node mapping in early stage endometrial and cervical cancer: comparison with conventional radiotracer Tc and/or blue dye.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Burke et al, 1996
      • Burke T.W.
      • Levenback C.
      • Tornos C.
      • Morris M.
      • Wharton J.T.
      • Gershenson D.M.
      Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high- risk endometrial cancer: results of a pilot study.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Darai, 2015
      • Morice P.
      • Leary A.
      • Creutzberg C.
      • Abu-Rustum N.
      • Darai E.
      Endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Delaloye et al, 2007
      • Delaloye J.-F.
      • Pampallona S.
      • Chardonnens E.
      • et al.
      Intraoperative lymphatic mapping and sentinel node biopsy using hysteroscopy in patients with endometrial cancer.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Desai et al, 2014
      • Desai P.H.
      • Hughes P.
      • Tobias D.H.
      • et al.
      Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC).
      YYNNRSelective pelvic and paraaortic lymphadenectomy (surgeon discretion)NNNRNY
      Eitan et al, 2015
      • Eitan R.
      • Sabah G.
      • Krissi H.
      • et al.
      Robotic blue-dye sentinel lymph node detection for endometrial cancer—factors predicting successful mapping.
      YYNNRPelvic lymphadenectomy if failed SLN mapping, surgeon discretion paraaortic LND (Memorial Sloan Kettering algorithm)NNNRYY
      Eriksson et al, 2016
      • St Clair C.M.
      • Eriksson A.G.Z.
      • Ducie J.A.
      • et al.
      Low-volume lymph node metastasis discovered during sentinel lymph node mapping for endometrial carcinoma.
      NRYNNRMemorial Sloan Kettering algorithmNNNRYY
      Farghali et al, 2015
      • Farghali M.M.
      • Allam I.S.
      • Abdelazim I.A.
      • et al.
      Accuracy of sentinel node in detecting lymph node metastasis in primary endometrial carcinoma.
      NRYYNRSelective pelvic and paraaortic lymphadenectomy by tumor grade, invasion depth, size, location, and patient fitnessNYNRNY
      Favero et al, 2015
      • Favero G.
      • Pfiffer T.
      • Ribeiro A.
      • et al.
      Laparoscopic sentinel lymph node detection after hysteroscopic injection of technetium-99 in patients with endometrial cancer.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYN
      Ferraioli et al, 2015
      • Ferraioli D.
      • Chopin N.
      • Beurrier F.
      • Carrabin N.
      • Buenerd A.
      • Mathevet P.
      The incidence and clinical significance of the micrometastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.
      NRNNNRPelvic and paraaortic lymphadenectomy if high riskYNNRYY
      Fersis et al, 2004
      • Fersis N.
      • Gruber I.
      • Relakis K.
      • et al.
      Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Frumovitz et al, 2007
      • Frumovitz M.
      • Bodurka D.C.
      • Broaddus R.R.
      • et al.
      Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYN
      Gien et al, 2005
      • Gien L.T.
      • Kwon J.S.
      • Carey M.S.
      Sentinel node mapping with isosulfan blue dye in endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Holloway et al, 2016
      • Holloway R.W.
      • Gupta S.
      • Stavitzski N.M.
      • et al.
      Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.
      YNNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYN
      Holub et al, 2004
      • Holub Z.
      • Jabor A.
      • Lukac J.
      • Kliment L.
      Laparoscopic detection of sentinel lymph nodes using blue dye in women with cervical and endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      How et al, 2012
      • How J.
      • Lau S.
      • Press J.
      • et al.
      Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study.
      YNNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      How et al, 2015
      • How J.
      • Gotlieb W.H.
      • Press J.Z.
      • et al.
      Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer.
      YNNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Kadkhodayan et al, 2014
      • Kadkhodayan S.
      • Shiravani Z.
      • Hasanzadeh M.
      • et al.
      Lymphatic mapping and sentinel node biopsy in endometrial cancer—a feasibility study using cervical injection of radiotracer and blue dye.
      YNNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Kataoka et al, 2016
      • Kataoka F.
      • Susumu N.
      • Yamagami W.
      • et al.
      The importance of para-aortic lymph nodes in sentinel lymph node mapping for endometrial cancer by using hysteroscopic radio-isotope tracer injection combined with subserosal dye injection: prospective study.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYN
      Koskas et al, 2013
      • Koskas M.
      • Chereau E.
      • Ballester M.
      • et al.
      Accuracy of a nomogram for prediction of lymph-node metastasis detected with conventional histopathology and ultrastaging in endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskNNNRYY
      Kuru et al, 2011
      • Kuru O.
      • Topuz S.
      • Sen S.
      • Iyibozkurt C.
      • Berkman S.
      Sentinel lymph node biopsy in endometrial cancer: description of the technique and preliminary results.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Laios et al, 2015
      • Laios A.
      • Volpi D.
      • Tullis I.D.C.
      • et al.
      A prospective pilot study of detection of sentinel lymph nodes in gynaecological cancers using a novel near infrared fluorescence imaging system.
      YYNNRComplete pelvic lymphadenectomyYNNRYY
      Lelievre et al, 2004
      • Lelievre L.
      • Camatte S.
      • Le Frere-belda M.A.
      • et al.
      Sentinel lymph node biopsy in cervix and corpus uteri cancers.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Li et al, 2009
      • Li B.
      • Wu L.
      • Li X.
      • et al.
      Sentinel lymph node identification in endometrial cancer.
      NRYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Lopes et al, 2007
      • Lopes L.A.F.
      • Nicolau S.M.
      • Baracat F.F.
      • et al.
      Sentinel lymph node in endometrial cancer.
      YYNNRPelvic and paraaortic lymphadenectomy if high riskNNNRYY
      Lopez-De la Manzanara et al, 2014
      • Lopez-De la Manzanara Cano C.
      • Cordero Garcia J.M.
      • et al.
      Sentinel lymph node detection using 99mTc combined with methylene blue cervical injection for endometrial cancer surgical management: a prospective study.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Mais et al, 2010
      • Mais V.
      • Peiretti M.
      • Gargiulo T.
      • Parodo G.
      • Cirronis M.G.
      • Melis G.B.
      Intraoperative sentinel lymph node detection by vital dye through laparoscopy or laparotomy in early endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Mosgaard et al, 2013
      • Mosgaard B.J.
      • Skovlund V.R.
      • Hendel H.W.
      Promising results using sentinel node biopsy as a substitute for radical lymphadenectomy in endometrial cancer staging.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Mucke et al, 2014
      • Mucke J.
      • Klapdor R.
      • Schneider M.
      • et al.
      Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Naaman et al, 2016
      • Naaman Y.
      • Pinkas L.
      • Roitman S.
      • et al.
      The added value of SPECT/CT in sentinel lymph nodes mapping for endometrial carcinoma.
      YYNNRComplete pelvic lymphadenectomy or Memorial Sloan Kettering algorithm, paraaortic lymphadenectomy if high riskNNNRNY
      Niikura et al, 2013
      • Niikura H.
      • Kaiho-Sakuma M.
      • Tokunaga H.
      • et al.
      Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Paley et al, 2016
      • Paley P.J.
      • Veljovich D.S.
      • Press J.Z.
      • Isacson C.
      • Pizer E.
      • Shah C.
      A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging.
      YYNNRPelvic and paraaortic lymphadenectomy if high riskNNNRYY
      Pandit-Taskar et al, 2010
      • Pandit-Taskar N.
      • Gemignani M.L.
      • Lyall A.
      • Larson S.M.
      • Barakat R.R.
      • Abu Rustum N.R.
      Single photon emission computed tomography SPECT-CT improves sentinel node detection and localization in cervical and uterine malignancy.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Papadia et al, 2016
      • Papadia A.
      • Imboden S.
      • Siegenthaler F.
      • et al.
      Laparoscopic indocyanine green sentinel lymph node mapping in endometrial cancer.
      YYNNRPelvic lymphadenectomy unless type I well differentiated <50% myometrial invasion, paraaortic lymphadenectomy if high riskNNNRYY
      Pelosi et al, 2003
      • Pelosi E.
      • Arena V.
      • Baudino B.
      • et al.
      Pre-operative lymphatic mapping and intra-operative sentinel lymph node detection in early stage endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Perrone et al, 2008
      • Perrone A.M.
      • Casadio P.
      • Formelli G.
      • et al.
      Cervical and hysteroscopic injection for identification of sentinel lymph node in endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Raimond et al, 2014
      • Schiavone M.B.
      • Zivanovic O.
      • Zhou Q.
      • et al.
      Survival of patients with uterine carcinosarcoma undergoing sentinel lymph node mapping.
      NRYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYN
      Raspagliesi et al, 2004
      • Raspagliesi F.
      • Ditto A.
      • Kusamura S.
      • et al.
      Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study.
      YYNNRPelvic lymphadenectomy if high riskNNNRYY
      Robova et al, 2009
      • Robova H.
      • Charvat M.
      • Strnad P.
      • et al.
      Lymphatic mapping in endometrial cancer: comparison of hysteroscopic and subserosal injection and the distribution of sentinel lymph nodes.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYN
      Rossi et al, 2013
      • Rossi E.C.
      • Jackson A.
      • Ivanova A.
      • Boggess J.F.
      Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRNY
      Sawicki et al, 2015
      • Sawicki S.
      • Lass P.
      • Wydra D.
      Sentinel Lymph Node Biopsy in Endometrial Cancer–Comparison of 2 Detection Methods.
      YYNNRPelvic and paraaortic lymphadenectomy if grade 3, >50% myometrial invasion, or cervical involvement; not if morbid obesity, advanced age, or poor general statusNNNRYY
      Schiavone et al, 2016
      • Ferraioli D.
      • Chopin N.
      • Beurrier F.
      • Carrabin N.
      • Mathevet P.
      The incidence and clinical significance of the micro-metastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.
      YNNNRSurgeon-discretion lymphadenectomy or Memorial Sloan Kettering algorithmNNNRNY
      Solima et al, 2012
      • Solima E.
      • Martinelli F.
      • Ditto A.
      • et al.
      Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer.
      YNNNRComplete pelvic or paraaortic lymphadenectomy if high riskYNNRYN
      St Clair et al, 2016
      • St Clair C.M.
      • Eriksson A.G.Z.
      • Ducie J.A.
      • et al.
      Low-volume lymph node metastasis discovered during sentinel lymph node mapping for endometrial carcinoma.
      YYNNRMemorial Sloan Kettering algorithmYNNRYY
      Tanner et al, 2015
      • Tanner E.J.
      • Sinno A.K.
      • Stone R.L.
      • Levinson K.L.
      • Long K.C.
      • Fader A.N.
      Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer.
      YYNNRComplete pelvic and paraaortic lymphadenectomy if high riskYNNRYY
      Torné et al, 2013
      • Torné A.
      • Pahisa J.
      • Vidal-Sicart S.
      • et al.
      Transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR): a new method for sentinel lymph node detection in endometrial cancer.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Touhami et al, 2015
      • Touhami O.
      • Trinh X.-B.
      • Gregoire J.
      • et al.
      Is a more comprehensive surgery necessary in patients with uterine serous carcinoma?.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymph node samplingYNNRYY
      Touhami et al, 2015
      • Touhami O.
      • Trinh X.-B.B.
      • Grégoire J.
      • et al.
      Predictors of non-sentinel lymph node metastasis in patients with positive sentinel lymph node (SLN) in endometrial cancer.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Valha et al, 2015
      • Valha P.
      • Kucera E.
      • Sak P.
      • Stepanek O.
      • Michal M.
      Intraoperative subserosal approach to label sentinel nodes in intermediate and high-risk endometrial cancer.
      YYNNRComplete pelvic and paraaortic lymphadenectomyYNNRYY
      Vidal et al, 2013
      • Vidal F.
      • Leguevaque P.
      • Motton S.
      • et al.
      Evaluation of the sentinel lymph node algorithm with blue dye labeling for early-stage endometrial cancer in a multicentric setting.
      YYNNRComplete pelvic lymphadenectomy, paraaortic lymphadenectomy if high riskYNNRYY
      Memorial Sloan Kettering algorithm indicates a pelvic lymphadenectomy if failed mapping, surgeon discretion paraaortic lymphadenectomy.
      LND, lymphadenectomy; N, no; NR, not reported; SLN, sentinel lymph node; Y, yes.
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.
      Appendix Table 2Univariate meta-regression of SLN sensitivity and study characteristics
      CharacteristicsSensitivity % (95% CI)P value
      Study size
       ≥30 patients0.97 (0.94–0.99).78
       <30 patients0.94 (0.85–1.00)
      Preoperative lymphoscintigraphy
       Yes0.98 (0.95–1.00).77
       No0.95 (0.91–0.99)
      Injection site
       Cervical0.97 (0.94–0.99).46
       Uterine0.94 (0.89–1.00)
      Radiotracer used
       Yes0.97 (0.95–1.00).71
       No0.94 (0.89–1.00)
      Dye and radiotracer used
       Yes0.97 (0.94–0.99).84
       No0.95 (0.86–1.00)
      Intraoperative frozen section
       Yes0.97 (0.92–1.00).55
       No0.97 (0.93–1.00)
      Ultrastaging
       Yes0.97 (0.94–0.99).90
       No0.94 (0.86–1.00)
      Bodurtha Smith. Sentinel lymph nodes and endometrial cancer, a meta-analysis. Am J Obstet Gynecol 2017.

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