Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics


      A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280).

      Data Sources

      We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. was searched to identify ongoing registered clinical trials.

      Study Eligibility Criteria

      We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data.


      We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.


      We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44–82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4–43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%–95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%–73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%–34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%–96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%–16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%–99%; I2=0%).


      Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2019.
        CA Cancer J Clin. 2019; 69: 7-34
        • Reeves G.K.
        • Pirie K.
        • Beral V.
        • et al.
        Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study.
        BMJ. 2007; 335: 1134
        • Clarke M.A.
        • Devesa S.S.
        • Harvey S.V.
        • Wentzensen N.
        Hysterectomy-corrected uterine corpus cancer incidence trends and differences in relative survival reveal racial disparities and rising rates of nonendometrioid cancers.
        J Clin Oncol. 2019; 37: 1895-1908
        • Setiawan V.W.
        • Yang H.P.
        • Pike M.C.
        • et al.
        Type I and II endometrial cancers: have they different risk factors?.
        J Clin Oncol. 2013; 31: 2607-2618
        • Concin N.
        • Matias-Guiu X.
        • Vergote I.
        • et al.
        ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma.
        Int J Gynecol Cancer. 2021; 31: 12-39
        • NCCN Clinical Practice Guidelines in Oncology, Uterine Neoplasms
        Version 2. 2020.
        (Available at:) (Accessed February 18, 2021)
        • Dowdy S.C.
        • Borah B.J.
        • Bakkum-Gamez J.N.
        • et al.
        Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer.
        Gynecol Oncol. 2012; 127: 5-10
        • Yost K.J.
        • Cheville A.L.
        • Al-Hilli M.M.
        • et al.
        Lymphedema after surgery for endometrial cancer: prevalence, risk factors, and quality of life.
        Obstet Gynecol. 2014; 124: 307-315
        • Frost J.A.
        • Webster K.E.
        • Bryant A.
        • Morrison J.
        Lymphadenectomy for the management of endometrial cancer.
        Cochrane Database Syst Rev. 2017; 10: CD007585
        • Barlin J.N.
        • Khoury-Collado F.
        • Kim C.H.
        • et al.
        The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes.
        Gynecol Oncol. 2012; 125: 531-535
        • Holloway R.W.
        • Abu-Rustum N.R.
        • Backes F.J.
        • et al.
        Sentinel lymph node mapping and staging in endometrial cancer: a Society of Gynecologic Oncology literature review with consensus recommendations.
        Gynecol Oncol. 2017; 146: 405-415
        • Cormier B.
        • Rozenholc A.T.
        • Gotlieb W.
        • Plante M.
        • Giede C.
        • Communities of Practice (CoP) Group of Society of Gynecologic Oncology of Canada (GOC)
        Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research.
        Gynecol Oncol. 2015; 138: 478-485
        • Burg L.C.
        • Hengeveld E.M.
        • In ’t Hout J.
        • Bulten J.
        • Bult P.
        • Zusterzeel P.L.M.
        Ultrastaging methods of sentinel lymph nodes in endometrial cancer - a systematic review.
        Int J Gynecol Cancer. 2021; 31: 744-753
        • 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.
        Gynecol Oncol. 2015; 136: 54-59
        • Rossi E.C.
        • Kowalski L.D.
        • Scalici J.
        • et al.
        A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study.
        Lancet Oncol. 2017; 18: 384-392
        • Persson J.
        • Salehi S.
        • Bollino M.
        • Lönnerfors C.
        • Falconer H.
        • Geppert B.
        Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)-the final step towards a paradigm shift in surgical staging.
        Eur J Cancer. 2019; 116: 77-85
        • Soliman P.T.
        • Westin S.N.
        • Dioun S.
        • et al.
        A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer.
        Gynecol Oncol. 2017; 146: 234-239
        • Cusimano M.C.
        • Vicus D.
        • Pulman K.
        • et al.
        Assessment of sentinel lymph node biopsy vs lymphadenectomy for intermediate- and high-grade endometrial cancer staging.
        JAMA Surg. 2020; 156: 157-164
        • Higgins J.P.T.
        • Thomas J.
        • Chandler J.
        • et al.
        Cochrane handbook for systematic reviews of interventions.
        John Wiley & Sons, Chichester, United Kingdom2019
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • PRISMA Group
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        PLoS Med. 2009; 6e1000097
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.
        JAMA. 2000; 283: 2008-2012
        • Hopewell S.
        • Clarke M.
        • Askie L.
        Reporting of trials presented in conference abstracts needs to be improved.
        J Clin Epidemiol. 2006; 59: 681-684
        • Toma M.
        • McAlister F.A.
        • Bialy L.
        • Adams D.
        • Vandermeer B.
        • Armstrong P.W.
        Transition from meeting abstract to full-length journal article for randomized controlled trials.
        JAMA. 2006; 295: 1281-1287
        • Morrison A.
        • Polisena J.
        • Husereau D.
        • et al.
        The effect of English-language restriction on systematic review-based meta-analyses: a systematic review of empirical studies.
        Int J Technol Assess Health Care. 2012; 28: 138-144
        • Bodurtha Smith A.J.
        • Fader A.N.
        • Tanner E.J.
        Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis.
        Am J Obstet Gynecol. 2017; 216: 459-476.e10
        • Bogani G.
        • Murgia F.
        • Ditto A.
        • Raspagliesi F.
        Sentinel node mapping vs. lymphadenectomy in endometrial cancer: a systematic review and meta-analysis.
        Gynecol Oncol. 2019; 153: 676-683
        • Whiting P.F.
        • Rutjes A.W.
        • Westwood M.E.
        • et al.
        QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.
        Ann Intern Med. 2011; 155: 529-536
        • R Core Team
        R: A language and environment for statistical computing.
        R Foundation for Statistical Computing, Vienna, Republic of Austria2018 (Available at:) (Accessed February 18, 2021)
        • Balduzzi S.
        • Rücker G.
        • Schwarzer G.
        How to perform a meta-analysis with R: a practical tutorial.
        Evid Based Ment Health. 2019; 22: 153-160
        • Backes F.J.
        • Cohen D.
        • Salani R.
        • et al.
        Prospective clinical trial of robotic sentinel lymph node assessment with isosulfane blue (ISB) and indocyanine green (ICG) in endometrial cancer and the impact of ultrastaging (NCT01818739).
        Gynecol Oncol. 2019; 153: 496-499
        • Cabrera S.
        • Bebia V.
        • Franco-Camps S.
        • et al.
        Technetium-99m-indocyanine green versus technetium-99m-methylene blue for sentinel lymph node biopsy in early-stage endometrial cancer.
        Int J Gynecol Cancer. 2020; 30: 311-317
        • Holloway R.W.
        • Ahmad S.
        • Kendrick J.E.
        • et al.
        A prospective cohort study comparing colorimetric and fluorescent imaging for sentinel lymph node mapping in endometrial cancer.
        Ann Surg Oncol. 2017; 24: 1972-1979
        • How J.
        • Boldeanu I.
        • Lau S.
        • et al.
        Unexpected locations of sentinel lymph nodes in endometrial cancer.
        Gynecol Oncol. 2017; 147: 18-23
        • Ianieri M.M.
        • Puppo A.
        • Novelli A.
        • et al.
        Sentinel lymph node biopsy in the treatment of endometrial cancer: why we fail? Results of a prospective multicenter study on the factors associated with failure of node mapping with indocyanine green.
        Gynecol Obstet Invest. 2019; 84: 383-389
        • Laios A.
        • Volpi D.
        • Tullis I.D.
        • et al.
        A prospective pilot study of detection of sentinel lymph nodes in gynaecological cancers using a novel near infrared fluorescence imaging system.
        BMC Res Notes. 2015; 8: 608
        • Lim Y.K.
        • Ho W.Y.
        • Wong W.L.
        • Aggarwal I.
        • Yam K.L.
        A pilot study on the use of indocyanine green near-infrared technique for sentinel lymph node biopsy in early endometrial cancers in Singapore.
        J Gynecol Surg. 2020; 36: 319-324
        • 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.
        Am J Obstet Gynecol. 2016; 215: 117.e1-117.e7
        • 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.
        Int J Gynecol Cancer. 2013; 23: 1704-1711
        • Taşkın S.
        • Şükür Y.E.
        • Altın D.
        • et al.
        Laparoscopic near-infrared fluorescent imaging as an alternative option for sentinel lymph node mapping in endometrial cancer: a prospective study.
        Int J Surg. 2017; 47: 13-17
        • Taşkın S.
        • Sarı M.E.
        • Altın D.
        • et al.
        Risk factors for failure of sentinel lymph node mapping using indocyanine green/near-infrared fluorescent imaging in endometrial cancer.
        Arch Gynecol Obstet. 2019; 299: 1667-1672
        • Ye L.
        • Li S.
        • Lu W.
        • et al.
        A prospective study of sentinel lymph node mapping for endometrial cancer: is it effective in high-risk subtypes?.
        Oncologist. 2019; 24: e1381-e1387
        • How J.A.
        • O’Farrell P.
        • Amajoud Z.
        • et al.
        Sentinel lymph node mapping in endometrial cancer: a systematic review and meta-analysis.
        Minerva Ginecol. 2018; 70: 194-214
        • Levenback C.F.
        • Ali S.
        • Coleman R.L.
        • et al.
        Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: a gynecologic oncology group study.
        J Clin Oncol. 2012; 30: 3786-3791
        • Kim T.
        • Giuliano A.E.
        • Lyman G.H.
        Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis.
        Cancer. 2006; 106: 4-16
        • Valsecchi M.E.
        • Silbermins D.
        • de Rosa N.
        • et al.
        Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma: a meta-analysis.
        J Clin Oncol. 2011; 29: 1479-1487
        • Cusimano M.C.
        • Walker R.
        • Bernardini M.Q.
        • et al.
        Implementing a cervical sentinel lymph node biopsy program: quality improvement in gynaecologic oncology.
        J Obstet Gynaecol Can. 2017; 39: 659-667
        • Kitchener H.
        • Swart A.M.
        • Qian Q.
        • Amos C.
        • Parmar M.K.
        • ASTEC study group
        Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.
        Lancet. 2009; 373: 125-136
        • Benedetti Panici P.
        • Basile S.
        • Maneschi F.
        • et al.
        Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.
        J Natl Cancer Inst. 2008; 100: 1707-1716
        • de Boer S.M.
        • Powell M.E.
        • Mileshkin L.
        • et al.
        Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial.
        Lancet Oncol. 2019; 20: 1273-1285
        • Plante M.
        • Stanleigh J.
        • Renaud M.C.
        • Sebastianelli A.
        • Grondin K.
        • Grégoire J.
        Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: does adjuvant treatment matter?.
        Gynecol Oncol. 2017; 146: 240-246
        • Ignatov A.
        • Lebius C.
        • Ignatov T.
        • et al.
        Lymph node micrometastases and outcome of endometrial cancer.
        Gynecol Oncol. 2019; 154: 475-479
        • Matei D.
        • Filiaci V.
        • Randall M.E.
        • et al.
        Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer.
        N Engl J Med. 2019; 380: 2317-2326
        • León-Castillo A.
        • de Boer S.M.
        • Powell M.E.
        • et al.
        Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy.
        J Clin Oncol. 2020; 38: 3388-3397
        • NCT04073706
        A phase III randomised clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer (ENDO-3).
        (Available at:)
        Date: 2021
        Date accessed: May 17, 2021
        • Geppert B.
        • Lönnerfors C.
        • Bollino M.
        • Persson J.
        Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.
        Gynecol Oncol. 2018; 148: 491-498
        • Abu-Rustum N.R.
        • Gomez J.D.
        • Alektiar K.M.
        • et al.
        The incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes.
        Gynecol Oncol. 2009; 115: 236-238
        • Kumar S.
        • Podratz K.C.
        • Bakkum-Gamez J.N.
        • et al.
        Prospective assessment of the prevalence of pelvic, paraaortic and high paraaortic lymph node metastasis in endometrial cancer.
        Gynecol Oncol. 2014; 132: 38-43