Highlights
- •Advances in molecular pathology complement clinical management of endometrial cancer.
- •Increased estrogen exposure and genetic predisposition remain important risk factors
- •Judicious evaluation of abnormal bleeding and cancer referrals to gynecologic oncologists optimize management
- •Most patients benefit from minimally invasive surgery and tailored lymph node evaluation.
- •Risk stratification based on recent trials should influence adjuvant therapy decisions.
Abstract
Introduction
In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published
a clinical update reviewing the treatment of women with endometrial cancer. At that
time, there had been significant advances in the diagnosis, work-up, surgical management,
and available treatment options allowing for more optimal care of affected women.
Despite these advances, the incidence of endometrial cancer as well as the deaths
attributable to the disease have continued to rise; from 1987 to 2014 there has been
a 75% increase in cases and almost 300% increase in endometrial cancer deaths. Fortunately,
since then, there has been progress in the treatment of patients with endometrial
cancer with increased utilization of molecular pathology, greater understanding of
genetic predisposition, enhanced methods for lymph node assessment, a broader understanding
of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship
and surveillance. The purpose of this document is to present a comprehensive review
of this progress.
Manuscript development process
The authors reviewed the available evidence, contributed to the development of this
manuscript, provided critical review of the guidelines, and finalized the manuscript
recommendations. The review was also presented to and approved by the Society of Gynecologic
Oncology (SGO) Clinical Practice Committee, SGO Publications Committee, and the SGO
board members prior to submission for publication.
The recommendations for this manuscript were developed by a panel of gynecologic oncologists
who were members of the SGO Clinical Practice and Education Committees. Panelists
reviewed and considered evidence from current uterine cancer literature. The terminology
used in these guidelines was adopted from the ASCCP management guidelines [
[1]
] using a two-part rating system to grade the strength of recommendation and quality
of evidence (Table 1). The rating for each recommendation is given in parentheses.Keywords
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 accessOne-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:
Subscribe to Gynecologic OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.Obstet. Gynecol. 2013; 121: 829-846https://doi.org/10.1097/AOG/0b013e31828883a34
- Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial.Lancet Oncol. 2019 May; 20 (Epub 2019 Mar 25): 711-718https://doi.org/10.1016/S1470-2045(19)30020-830922731
- Template for Reporting Results of Biomarker Testing of Specimens from Patients with Carcinoma of the Endometrium. Version: Endometrium Biomarkers 1.2.0.1.(Accessed at)
- Two pathogenetic types of endometrial carcinoma.Gynecol. Oncol. 1983 Feb; 15 (PMID: 6822361): 10-17https://doi.org/10.1016/0090-8258(83)90111-7
- Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation.Hum. Pathol. 1995 Nov; 26 (PMID: 7590702): 1260-1267https://doi.org/10.1016/0046-8177(95)90203-1
- Endometrial cancer: molecular markers and management of advanced stage disease.Gynecol. Oncol. 2018 Sep; 150 (Epub 2018 May 27. PMID: 29843906): 569-580https://doi.org/10.1016/j.ygyno.2018.05.015
- Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers.Br. J. Cancer. 2006; 94: 642-646
- Interobserver agreement in endometrial carcinoma Histotype diagnosis varies depending on the Cancer genome atlas (TCGA)-based molecular subgroup.Am. J. Surg. Pathol. 2017; 41: 245-252
- Interobserver variability in the diagnosis of uterine high-grade Endometrioid carcinoma.Arch Pathol Lab Med. 2016; 140: 836-843
- Integrated genomic characterization of endometrial carcinoma [published correction appears in Nature. 2013 Aug 8;500(7461):242].Nature. 2013; 497: 67-73https://doi.org/10.1038/nature12113
- Molecular approaches for classifying endometrial carcinoma.Gynecol. Oncol. 2017 Apr; 145 (Epub 2016 Dec 29): 200-207https://doi.org/10.1016/j.ygyno.2016.12.01528040204
- Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series.Ann Oncol. 2018; 29: 1180-1188
- An NRG oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer.Gynecol. Oncol. 2018; 148: 174-180
- Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy.J Clin Oncol. 2020 Oct 10; 38 (Epub 2020 Aug 4. PMID: 32749941; PMCID: PMC7527156): 3388-3397https://doi.org/10.1200/JCO.20.00549
- Evolving roles of histologic evaluation and molecular/genomic profiling in the Management of Endometrial Cancer.J. Natl. Compr. Cancer Netw. 2018; 16: 201-209
- Society of gynecologic oncology clinical practice committee. endometrial cancer: a review and current management strategies: part I.Gynecol Oncol. 2014 Aug; 134 (Epub 2014 Jun 4. Erratum in: Gynecol Oncol. 2014 Dec;135(3):625. Villella, Jeanine [corrected to Villella, Jeannine]. PMID: 24905773): 385-392https://doi.org/10.1016/j.ygyno.2014.05.018
- Practice Bulletin No. 149: Endometrial cancer.Obstet. Gynecol. 2015 Apr; 125 (PMID: 25798986): 1006-1026https://doi.org/10.1097/01.AOG.0000462977.61229.de
- Endometrial cancer in tamoxifen treated breast cancer patients: findings from the national surgical adjuvant breast and bowel project.J Natl Cancer Institute. 1994; 86: 527-537
- Multi-disciplinary summit on genetics services for women with gynecologic cancers: a Society of Gynecologic Oncology White Paper.Gynecol. Oncol. 2017; 146: 217-224
- Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort.Mod Pathol. 2016 Nov; 29 (Epub 2016 Jul 22. PMID: 27443514; PMCID: PMC5541389): 1381-1389https://doi.org/10.1038/modpathol.2016.135
- ACOG Practice Bulletin No. 147: lynch syndrome.Obstet. Gynecol. 2014 Nov; 124 (PMID: 25437740): 1042-1054https://doi.org/10.1097/01.AOG.0000456325.50739.72
- ACOG Committee Opinion No. 734: the role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding.Obstet. Gynecol. 2018 May; 131 (PMID: 29683909): e124-e129https://doi.org/10.1097/AOG.0000000000002631
- The use of transvaginal ultrasound in type II endometrial Cancer.Int. J. Gynecol. Cancer. 2015 Jun; 25 (PMID: 25768078): 858-862https://doi.org/10.1097/IGC.0000000000000423
- Role of bleeding recognition and evaluation in Black White disparities in endometrial cancer.Am J Obstet Gynecol. 2018; 219 (e1–14): 593
- Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: gynecologic oncology group study LAP2.J. Clin. Oncol. 2009; 27: 5331-5336
- Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial.Lancet Oncol. 2010; 11: 772-780
- Safety of laparoscopy versus laparotomy in early-stage endometrial cancer: a randomised trial.Lancet Oncol. 2010; 11: 763-771
- Effect of Total laparoscopic hysterectomy vs Total abdominal hysterectomy on disease-free survival among women with stage I endometrial Cancer: a randomized clinical trial.JAMA. 2017 Mar 28; 317: 1224-1233https://doi.org/10.1001/jama.2017.206828350928
- Impact of histology and surgical approach on survival among women with early-stage, high-grade uterine cancer: An NRG Oncology/Gynecologic Oncology Group ancillary analysis.Gynecol Oncol. 2016 Dec; 143 (Epub 2016 Oct 12. PMID: 27743738; PMCID: PMC5116702): 460-465https://doi.org/10.1016/j.ygyno.2016.10.016
- Robotic surgery in gynecologic oncology: program initiation and outcomes after the first year with comparison with laparotomy for endometrial cancer staging.Am J Obstet Gynecol. 2008; 198 (e671–679; discussion 679 e679–610): 679
- Robotic hysterectomy and lymphadenectomy for endometrial cancer: technical aspects and details of success-the Ohio State University method.J. Robot. Surg. 2008; 2: 71-76
- A comparative study of 3 surgical methods for hysterectomy with staging for endometrial cancer: robotic assistance, laparoscopy, laparotomy.Am J Obstet Gynecol. 2008; 199 (e1–9): 360
- Robotic surgery in supermorbidly obese patients with endometrial cancer.Am J Obstet Gynecol. 2015 Jul; 213 (e1–49.e8) (Epub 2015 Jan 30. PMID: 25644437): 49
- Prospective cohort study comparing quality of life and sexual health outcomes between women undergoing robotic, laparoscopic and open surgery for endometrial cancer.Gynecol. Oncol. 2018; 149: 476-483
- The role of vaginal hysterectomy in the treatment of endometrial cancer.Am J Obstet Gynecol. 2007 Aug; 197 (e1–6; discussion 202.e6–7) (PMID: 17689651): 202
- Use of a novel sentinel lymph node mapping algorithm reduces the need for pelvic lymphadenectomy in low-grade endometrial cancer.Gynecol. Oncol. 2017; 147: 535-540https://doi.org/10.1016/j.ygyno.2017.10.020
- Surgical pathologic spread patterns of endometrial cancer.A Gynecologic Oncology Group Study. Cancer. 1987; 60: 2035-2041
- Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary?.Am. J. Obstet. Gynecol. 2000; 182: 1506-1519
- Frozen section analyses as predictors of lymphatic spread in patients with early-stage uterine cancer.J. Am. Coll. Surg. 2004 Sep; 199: 388-393https://doi.org/10.1016/j.jamcollsurg.2004.05.25815325608
- Reproducibility of the diagnosis of atypical endometrial hyperplasia: a gynecologic oncology group study.Cancer. 2006; 106: 804-811
- Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.J. Natl. Cancer Inst. 2008; 100: 1707-1716
- Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.Lancet. 2009 Jan 10; 373 (Epub 2008 Dec 16. Erratum in: Lancet. 2009 May 23;373(9677):1764. PMID: 19070889; PMCID: PMC2646126): 125-136https://doi.org/10.1016/S0140-6736(08)61766-3
- Risk factors and recurrent patterns in stage I endometrial cancer.Am. J. Obstet. Gynecol. 1985 Apr 15; 151 (PMID: 3985062): 1009-1015https://doi.org/10.1016/0002-9378(85)90371-0
- Classification and regression tree (CART) analysis of endometrial carcinoma: seeing the forest for the trees.Gynecol. Oncol. 2013; 130: 452-456
- Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer.Gynecol. Oncol. 2012; 127: 5-10
- Lymphedema after surgery for endometrial cancer: prevalence, risk factors, and quality of life.Obstet. Gynecol. 2014; 124: 307-315
- Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection.Int. J. Gynecol. Cancer. 2013; 23: 1704-1711
- Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluorescence imaging for uterine and cervical malignancies.Gynecol. Oncol. 2014; 133: 274-277
- Sentinel node mapping with indocyanine green and endoscopic near-infrared fluorescence imaging in endometrial cancer. A pilot study and review of the literature.Gynecol. Oncol. 2015; 137: 443-447
- A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging.Am J Obstet Gynecol. 2016; 215 (e111–117): 117
- Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.Gynecol. Oncol. 2016; 141: 206-210
- Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO).Lancet Oncol. 2011; 12: 469-476
- 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
- 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
- A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer.Gynecol. Oncol. 2017; 146: 234-239https://doi.org/10.1016/j.ygyno.2017.05.016
- Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.Gynecol Oncol. 2016 Mar; 140 (Epub 2015 Dec 31. PMID: 26747778; PMCID: PMC4839486): 394-399https://doi.org/10.1016/j.ygyno.2015.12.028
- Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease.Gynecol. Oncol. 2017 Dec; 147 (Epub 2017 Sep 29. PMID: 28965698): 541-548https://doi.org/10.1016/j.ygyno.2017.09.030
- Multicenter study comparing oncologic outcomes between two nodal assessment methods in patients with deeply invasive endometrioid endometrial carcinoma: A sentinel lymph node algorithm versus a comprehensive pelvic and paraaortic lymphadenectomy.Gynecol Oncol. 2018 Nov; 151 (Epub 2018 Aug 31. PMID: 30177461; PMCID: PMC6214768): 235-242https://doi.org/10.1016/j.ygyno.2018.08.022
- Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths.Am J Obstet Gynecolog. 2008; (e1–218.e6): 218
- Advanced stage (IIIC/IV) endometrial cancer: role of cytoreduction and determinants of survival.Eur. J. Obstet. Gynecol. Reprod. Biol. 2018; 234: 26-31
- Surgical cytoreduction in stage IV endometrioid endometrial carcinoma.Gynecol. Oncol. 2011; 122: 608-611
- Surgical stage IV endometrial carcinoma: a study of 47 cases.Gynecol. Oncol. 1994; 52: 237-240
- Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival.Gynecol. Oncol. 2000; 78: 85-91
- Surgical treatment of recurrent endometrial carcinoma.Cancer. 2004; 100: 89-96
- Radical pelvic resection and intraoperative radiation therapy for recurrent endometrial cancer: technique and analysis of outcomes.Gynecol. Oncol. 2006; 101: 280-286
- Salvage cytoreductive surgery for recurrent endometrial cancer.Gynecol. Oncol. 2006; 103: 281-287
- Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer.Int. J. Radiat. Oncol. Biol. Phys. 2005 Oct 1; 63: 500-504https://doi.org/10.1016/j.ijrobp.2005.02.00416168841
- Pelvic exenteration for recurrent endometrial cancer.Gynecol. Oncol. 1999; 75: 99-102
- A phase III trial of surgery with our without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a gynecologic oncologic group study.Gynecol. Oncol. 2004; 92: 744-751
- Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicenter randomized trial.Lancet. 2000; 355: 1404-1411
- Phase III trial: adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/carboplatin in high-intermediate and high-risk early stage endometrial Cancer.J. Clin. Oncol. 2019; 37: 1810-1818
- Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label non-inferiority, randomized trial.Lancet. 2010; (23): 375-816
- Adjuvant radiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicenter, randomized, phase 3 trial.Lancet. 2018; 19: 295-309
- Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review and meta-analysis.Lancet. 2009; 373: 137-146
- Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer-results from two randomized studies.Eur. J. Cancer. 2010; 46: 2422-2431
- Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer.N Engl J Med. 2019 Jun 13; 380 (PMID: 31189035; PMCID: PMC6948006): 2317-2326https://doi.org/10.1056/NEJMoa1813181
- PORTEC Study Group. Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy.Br J Cancer. 2018 Oct; 119 (Epub 2018 Oct 25. PMID: 30356126; PMCID: PMC6219495): 1067-1074https://doi.org/10.1038/s41416-018-0310-8
- Long-term impact of endometrial Cancer diagnosis and treatment on health-related quality of life and Cancer survivorship: results from the randomized PORTEC-2 trial.Int. J. Radiat. Oncol. Biol. Phys. 2015 Nov 15; 93 (Epub 2015 Aug 18. PMID: 26530748): 797-809https://doi.org/10.1016/j.ijrobp.2015.08.023
- Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a gynecologic oncology group study.J. Clin. Oncol. 2006; 24: 36-44
- PORTEC Study Group. 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 Sep; 20 (Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. PMID: 31345626; PMCID: PMC6722042): 1273-1285https://doi.org/10.1016/S1470-2045(19)30395-X
- Kudo R; Japanese gynecologic oncology group. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese gynecologic oncology group study.Gynecol. Oncol. 2008 Jan; 108 (Epub 2007 Nov 9. PMID: 17996926): 226-233https://doi.org/10.1016/j.ygyno.2007.09.029
- Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial.Br J Cancer. 2006 Aug 7; 95 (Epub 2006 Jul 25. PMID: 16868539; PMCID: PMC2360651): 266-271https://doi.org/10.1038/sj.bjc.6603279
- Benefit of combination chemotherapy and radiation stratified by grade of stage IIIC endometrial cancer.Gynecol. Oncol. 2017 Nov; 147 (Epub 2017 Sep 13. PMID: 28916118): 309-314https://doi.org/10.1016/j.ygyno.2017.08.031
- Who benefits from chemoradiation in stage III-IVa endometrial cancer? An analysis of the National Cancer Data Base.Gynecol. Oncol. 2016; 142: 54-61
- Utilization of adjuvant therapies and their impact on survival for women with stage IIIC endometrial adenocarcinoma.Gynecol. Oncol. 2016; 142: 514-519
- Association of chemotherapy and radiotherapy sequence with overall survival in locoregionally advanced endometrial cancer.Gynecol. Oncol. 2019 Apr; 153 (Epub 2019 Jan 16): 41-48https://doi.org/10.1016/j.ygyno.2019.01.00730660345
- Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a gynecologic oncology group study.J. Clin. Oncol. 2004 Jun 1; 22: 2159-2166https://doi.org/10.1200/JCO.2004.07.18415169803
- Late-Breaking Abstract 1: Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: A Gynecologic Oncology Group study.Gynecol. Oncol. 2012; 125: 771
- A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer.Gynecol. Oncol. 2018; 150: 274-281
- Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-Trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu.J. Clin. Oncol. 2018; 36: 2044-2051
- Phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group study.J Clin Oncol. 2010 Jun 1; 28 (Epub 2010 Apr 26. PMID: 20421537; PMCID: PMC2881851): 2727-2731https://doi.org/10.1200/JCO.2009.26.8326
- A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus.Gynecol Oncol. 2007 Nov; 107 (Epub 2007 Sep 5. PMID: 17822748; PMCID: PMC2752331): 177-185https://doi.org/10.1016/j.ygyno.2007.07.070
- A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: a gynecologic oncology group study.Gynecol. Oncol. 2000 Nov; 79: 147-153https://doi.org/10.1006/gyno.2000.600111063636
- Ueland FR; gynecologic oncology group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a gynecologic oncology group study.J. Clin. Oncol. 2007 Feb 10; 25: 526-531https://doi.org/10.1200/JCO.2006.06.490717290061
- A Randomized Phase 3 Trial of Paclitaxel (P) & Carboplatin (C) Vs. P & Ifosfamide (I) in Chemotherapy-Naive Patients with Stage I-IV, Persistent or Recurrent Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial.ASCO (American Society of Clinical Oncology). 5/31/2019; (suppl; abstr 5500)
Article info
Publication history
Published online: January 27, 2021
Accepted:
December 19,
2020
Received:
August 13,
2020
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
