FIGO staging of endometrial cancer: 2023

INTRODUCTION Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies. METHODS The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system. RESULTS Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. Stage II (IIA): non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. Stage III (IIIA): differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. Stage IV (IVA): locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (POLEmut, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or POLEmut status in Stages I and II, this results in upstaging or downstaging of the disease (IICmp53abn or IAmPOLEmut ). SUMMARY The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.

[1]  A. Talhouk,et al.  Grade and Estrogen Receptor Expression Identify a Subset of No Specific Molecular Profile Endometrial Carcinomas at a Very Low Risk of Disease-Specific Death. , 2023, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[2]  C. Genestie,et al.  Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry , 2022, British Journal of Cancer.

[3]  A. Mariani,et al.  A novel algorithm to implement the molecular classification according to the new ESGO/ESTRO/ESP 2020 guidelines for endometrial cancer , 2022, International Journal of Gynecological Cancer.

[4]  Yu Xu,et al.  Incidence of omental metastasis in uterine serous carcinoma: a systematic review and meta-analysis. , 2022, Journal of gynecology obstetrics and human reproduction.

[5]  E. Ratner,et al.  Minimal Uterine Serous Carcinoma and Endometrial Polyp: A Close Clinicopathological Relationship. , 2021, Human pathology.

[6]  S. Marnitz,et al.  ESGO/ESTRO/ESP Guidelines for the management of patients with endometrial carcinoma , 2021, Virchows Archiv.

[7]  E. Leung,et al.  Substantial lymphovascular space invasion predicts worse outcomes in early-stage endometrioid endometrial cancer. , 2021, Brachytherapy.

[8]  G. Scambia,et al.  Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer , 2021, Journal of gynecologic oncology.

[9]  Cyrus Chargari,et al.  ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. , 2021, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  Cyrus Chargari,et al.  ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma , 2020, International Journal of Gynecological Cancer.

[11]  R. Bhargava,et al.  Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? - A single-institution study. , 2020, Gynecologic Oncology.

[12]  Hui Li,et al.  Prognostic value of different metastatic sites for patients with FIGO stage IVB endometrial cancer after surgery: A SEER database analysis , 2020, Journal of surgical oncology.

[13]  D. Boll,et al.  Incidence and predictors of peritoneal metastases of gynecological origin: a population-based study in the Netherlands , 2020, Journal of gynecologic oncology.

[14]  C. Aghajanian,et al.  Incidence of pelvic lymph node metastasis using modern FIGO staging and sentinel lymph node mapping with ultrastaging in surgically staged patients with endometrioid and serous endometrial carcinoma. , 2020, Gynecologic oncology.

[15]  T. Bosse,et al.  Incorporation of molecular characteristics into endometrial cancer management , 2019, Histopathology.

[16]  C. Gilks,et al.  Interpretation of somatic POLE mutations in endometrial carcinoma , 2019, The Journal of pathology.

[17]  C. Gilks,et al.  Clinicopathological and molecular characterisation of ‘multiple‐classifier’ endometrial carcinomas , 2019, The Journal of pathology.

[18]  J. Lang,et al.  The prognosis of stage IA synchronous endometrial endometrioid and ovarian carcinomas , 2019, Archives of Gynecology and Obstetrics.

[19]  J. McAlpine,et al.  Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer. , 2019, Gynecologic oncology.

[20]  C. Genestie,et al.  Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer , 2019, Histopathology.

[21]  A. Mariani,et al.  Low-volume disease in endometrial cancer: The role of micrometastasis and isolated tumor cells. , 2019, Gynecologic oncology.

[22]  A. Berchuck,et al.  Associations between lymphovascular space invasion, nodal recurrence, and survival in patients with surgical stage I endometrioid endometrial adenocarcinoma , 2019, World Journal of Surgical Oncology.

[23]  H. Yoshida,et al.  Prognostic factors of synchronous endometrial and ovarian endometrioid carcinoma , 2018, Journal of gynecologic oncology.

[24]  K. Matsuo,et al.  Prognosis of women with stage I endometrioid endometrial cancer and synchronous stage I endometrioid ovarian cancer. , 2017, Gynecologic oncology.

[25]  M. Plante,et al.  Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: Does adjuvant treatment matter? , 2017, Gynecologic oncology.

[26]  Ludmila V. Danilova,et al.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade , 2017, Science.

[27]  R. Sanz-Pamplona,et al.  Molecular approaches for classifying endometrial carcinoma. , 2017, Gynecologic oncology.

[28]  C. Compton,et al.  The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging , 2017, CA: a cancer journal for clinicians.

[29]  A. Talhouk,et al.  Confirmation of ProMisE: A simple, genomics‐based clinical classifier for endometrial cancer , 2017, Cancer.

[30]  M. Leitao,et al.  Low-Volume Lymph Node Metastasis Discovered During Sentinel Lymph Node Mapping for Endometrial Carcinoma , 2016, Annals of Surgical Oncology.

[31]  J. Ledermann,et al.  ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer , 2015, International Journal of Gynecologic Cancer.

[32]  N. Sakuragi,et al.  Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer , 2015, Journal of gynecologic oncology.

[33]  T. Bosse,et al.  Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer--A pooled analysis of PORTEC 1 and 2 trials. , 2015, European journal of cancer.

[34]  A. Talhouk,et al.  A clinically applicable molecular-based classification for endometrial cancers , 2015, British Journal of Cancer.

[35]  A. Viale,et al.  Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas. , 2015, Journal of the National Cancer Institute.

[36]  Yi Kan Wang,et al.  Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality. , 2015, Journal of the National Cancer Institute.

[37]  D. Lambrechts,et al.  Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer , 2014, Journal of the National Cancer Institute.

[38]  Steven J. M. Jones,et al.  Integrated genomic characterization of endometrial carcinoma , 2013, Nature.

[39]  P. Cross,et al.  Tumour‐free distance from serosa is a better prognostic indicator than depth of invasion and percentage myometrial invasion in endometrioid endometrial cancer , 2012, BJOG : an international journal of obstetrics and gynaecology.

[40]  S. Siesling,et al.  Outcome of Endometrial Cancer Stage IIIA with Adnexa or Serosal Involvement Only , 2011, Obstetrics and gynecology international.

[41]  S. Pecorelli Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium , 2009 .

[42]  J. Rabban,et al.  Minimal uterine serous carcinoma: current concepts in diagnosis and prognosis. , 2007, Pathology.

[43]  Christopher P Crum,et al.  The Tubal Fimbria Is a Preferred Site for Early Adenocarcinoma in Women With Familial Ovarian Cancer Syndrome , 2006, The American journal of surgical pathology.

[44]  Jaime Prat,et al.  Prognostic parameters of endometrial carcinoma. , 2004, Human pathology.

[45]  N. Ramirez,et al.  Is there a prognostic difference between depth of myometrial invasion and the tumor-free distance from the uterine serosa in endometrial cancer? , 2003, Gynecologic oncology.

[46]  V. Abeler,et al.  Carcinoma of the endometrium in Norway: a histopathological and prognostic survey of a total population , 1991, International Journal of Gynecologic Cancer.

[47]  G. Turashvili,et al.  Risk-based stratification of carcinomas concurrently involving the endometrium and ovary. , 2019, Gynecologic oncology.

[48]  R. Soslow Practical issues related to uterine pathology: staging, frozen section, artifacts, and Lynch syndrome , 2016, Modern Pathology.

[49]  E. Oliva,et al.  Endocervical involvement in endometrial adenocarcinoma is not prognostically significant and the pathologic assessment of the pattern of involvement is not reproducible. , 2013, Gynecologic oncology.

[50]  P. Goodfellow,et al.  Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer. , 2012, Gynecologic oncology.

[51]  D. Cohn,et al.  Prospective evaluation of prognostic significance of the tumor-free distance from uterine serosa in surgically staged endometrial adenocarcinoma. , 2009, Gynecologic oncology.

[52]  M. Kelly,et al.  Minimal uterine serous carcinoma: a clinicopathological study of 40 cases , 2005, Modern Pathology.