[en] [en] OBJECTIVE: Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification.
METHODS: The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens.
RESULTS: Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001).
CONCLUSIONS: Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.
Disciplines :
Oncology Surgery Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Chacon, Enrique ; Department of Gynecologic Oncology, Universidad de Navarra, Pamplona, Navarra, Spain echaconc@unav.es
Boria, Felix ; Hospital Universitario Nuestra Senora de la Candelaria, Santa Cruz de Tenerife, Spain
Lyer, R Rajagopalan ; Department of Gynecologic Oncology, Basavatarakam Indo-American Cancer Institute and Research Centre, Hyderabad, Telangana, India
Fanfani, Francesco; Department of Women, Children and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Malzoni, Mario; Endoscopica Malzoni, Center for Advanced Endoscopic Gynecologic Surgery, Center for Advanced Endoscopic Gynecologic Surgery, Avellino, Italy
Bretová, Petra ; Department of Obstetrics and Gynecology, Brno University Hospital, Brno, Czech Republic, Czech Republic
Luzarraga Aznar, Ana ; Department of Gynecologic Oncology, Hospital Vall d'Hebron, Barcelona, Spain
Fruscio, Robert ; Department of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy ; Clinic of Obstetrics and Gynecology, Hospital San Gerardo, Monza, Italy
Jedryka, Marcin A ; Department of Oncological Gynecology, Lower Silesian Oncology Center Wrocław, Wroclaw, Poland ; Department of Gynecological Oncology, Wroclaw Medical University, Wroclaw, Poland
Tóth, Richard ; Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
Perrone, Anna Myriam ; Universitaria di Bologna, Bologna, Italy
Kakkos, Athanasios; Department of Obstetrics and Gynecology, CHU de Liège, Liege, Belgium
Cristóbal Quevedo, Ignacio ; Department of Obstetrics and Gynecology, La Paz University Hospital, Madrid, Madrid, Spain
Congedo, Luigi; Department of Woman and Child Health Sciences, University Hospital Agostino Gemelli, Roma, Lazio, Italy ; Department of Gynecologic Oncology, Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Vlaams-Brabant, Belgium
Zanagnolo, Vanna; Istituto Europeo di Oncologia, Milano, Anognnn, Italy
Fernandez-Gonzalez, Sergi ; Department of Gynecology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
Ferro, Beatriz; Department of Obstetrics and Gynecology, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Coimbra, Portugal
Narducci, Fabrice; Department of Gynecology, Centre Oscar Lambret, Lille, France
Hovhannisyan, Tatevik; Department of Gynecologic Oncology, Nairi Medical Center, Yerevan, Armenia
Aksahin, Elif; Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine, Fatih, Istanbul, Turkey
Cardenas, Laura; Gynecologic Oncology Unit, Hospital Universitario de Girona Doctor Josep Trueta, Girona, Catalunya, Spain
Oliver, M Reyes; Department of Gynaecologic Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
Nozaleda, Gonzalo; Department of Obstetrics and Gynecology, Hospital General Universitario Gregorio Marañón, Madrid, Madrid, Spain
Arnaez, Marta ; Department of Gynecologic Oncology, University Hospital La Fe, Valencia, Valencia, Spain
Misiek, Marcin; Holycross Cancer Center, Kielce, Poland
Ferrero, Annamaria; Department of Gynecology and Obstetrics, Mauriziano Hospital, Torino, Italy
Pain, Flore Anne; Department of Obstetrics and Gynecology, Hospital Lariboisière, Paris, France
Diaz, Cristina; Department of Obstetrics and Gynecology, Fundación Instituto Valenciano de Oncologia, Valencia, Spain
Ceppi, Lorenzo; ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
Mehdiyev, Shamsi; Department of Obstetrics and Gynecology, Bezmialem Vakif Universitesi, Istanbul, Istanbul, Turkey
Roldán-Rivas, Fernando; Department of Obstetrics and Gynaecology, Clinico Lozano Blesa Hospital, Zaragoza, Spain ; Universitat de Barcelona, Barcelona, Spain
Guijarro-Campillo, Alberto Rafael ; Department of Obstetrics and Gynecology, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Spain
Amengual, Joana ; Department of Gynaecology, Son Espases University Hospital, Palma de Mallorca, Spain
Manzour, Nabil ; Departamento de Ginecologia y Obstetricia, Clinica Universidad de Navarra, Pamplona, Navarra, Spain
Sanchez Lorenzo, Luisa ; Department of Medical Oncology, Clinica Universidad de Navarra, Madrid, Spain
Núñez-Córdoba, Jorge M; Clinica Universidad de Navarra, Pamplona, Navarra, Spain
Gonzalez Martin, Antonio ; Department of Medical Oncology, Clinica Universidad de Navarra, Madrid, Spain
Minguez, Jose Angel ; Department of Gynecology, Clinica Universidad de Navarra, Pamplona, Navarra, Spain
Chiva, Luis ; Departamento de Ginecologia y Obstetricia, Clinica Universidad de Navarra, Pamplona, Navarra, Spain
Corpus uteri source: globocan 2020. 2020. Available: https://gco. iarc.fr/today
Kitchener H, Swart AMC, Qian Q, et al. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet 2009;373:125-36.
Burke WM, Orr J, et al, SGO Clinical Practice Endometrial Cancer Working Group. Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol 2014;134:385-92.
Persson J, Salehi S, Bollino M, et al. 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.
Cusimano MC, Vicus D, Pulman K, et al. Assessment of sentinel lymph node biopsy vs lymphadenectomy for Intermediate-And high-grade endometrial cancer staging. JAMA Surg 2021;156:157-64.
Frumovitz M, Plante M, Lee PS, et al. Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial. Lancet Oncol 2018;19:1394-403.
Rossi EC, Kowalski LD, 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;18:384-92.
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.
Abu-Rustum NR. Sentinel lymph node mapping for endometrial cancer: a modern approach to surgical staging. J Natl Compr Canc Netw 2014;12:288-97.
GetzG, GabrielSB, Cibulskis K, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497:67-73.
Talhouk A, McConechy MK, Leung S, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 2015;113:299-310.
Talhouk A, McConechy MK, Leung S, et al. Confirmation of promise: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 2017;123:802-13.
Kommoss S, McConechy MK, Kommoss F, et al. Final validation of the promise molecular classifier for endometrial carcinoma in a large population-based case series. Ann Oncol 2018;29:1180-8.
León-Castillo A, de Boer SM, Powell ME, 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;38:3388-97.
Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009;105:103-4.
Tsujimoto M, Nakabayashi K, Yoshidome K, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res 2007;13:4807-16.
Dundr P, Cibula D, Nemejcová K, et al. Pathologic protocols for sentinel lymph nodes ultrastaging in cervical cancer. Arch Pathol Lab Med 2019;144:1011-20.
Moloney K, Janda M, Frumovitz M, et al. Development of a surgical competency assessment tool for sentinel lymph node dissection by minimally invasive surgery for endometrial cancer. Int J Gynecol Cancer 2021;31:647-55.
La Fera E, Bizzarri N, Petrecca A, et al. Evaluation of the one-step nucleic acid amplification method for rapid detection of lymph node metastases in endometrial cancer: prospective, multicenter, comparative study. Int J Gynecol Cancer 2023;33:1063-9.
Cucinella G, Schivardi G, Zhou XC, et al. Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study. Int J Gynecol Cancer 2024;34:179-87.
Hsu HC, Ramirez PT. Isolated tumor cells in low-risk endometrial cancer: are we ready for treatment decisions in 'isolation'? Int J Gynecol Cancer 2024;34:188-9.
Jamieson A, Thompson EF, Huvila J, et al. Endometrial carcinoma molecular subtype correlates with the presence of lymph node metastases. Gynecol Oncol 2022;165:376-84.
Bjørnholt SM, Sponholtz SE, Mogensen O, et al. The SENTIREC-endo study - risks and benefits of a national adoption of sentinel node mapping in low and intermediate risk endometrial cancer. Gynecol Oncol 2023;171:121-8.
Berek JS, Matias-Guiu X, Creutzberg C, et al. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet 2023;162:383-94.
Schwameis R, Fanfani F, Ebner C, et al. Verification of the prognostic precision of the new 2023 FIGO staging system in endometrial cancer patients -An international pooled analysis of three ESGO accredited centres. Eur J Cancer 2023;193.
Amant F, McCluggage WG, Werner HMJ, et al. Incorporating molecular profiling into endometrial cancer management requires prospective studies. Int J Gynecol Cancer 2021;31:944-5.
Bogani G, Lalli L, Casarin J, et al. Predicting the risk of nOdal disease with histological and molecular features in endometrial cancer: the prospective PROME trial. Int J Gynecol Cancer 2024;34:1366-72.
Abdulfatah E, Wakeling E, Sakr S, et al. Molecular classification of endometrial carcinoma applied to endometrial biopsy specimens: towards early personalized patient management. Gynecol Oncol 2019;154:467-74.
Cabrera S, Bebia V, López-Gil C, et al. Molecular classification improves preoperative risk assessment of endometrial cancer. Gynecol Oncol 2024;189:56-63.
Kasius JC, Trozzi R, Pijnenborg J, et al. Improving endometrial cancer assessment by combining the new techniqUe of GENomic profiling with surgical extra uterIne disEase assessment (EUGENIE). Int J Gynecol Cancer 2023;33:823-6.
