{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:43:57Z","timestamp":1787741037643,"version":"build-2784847793"},"reference-count":45,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>(1) Background: Endometrial cancer (EC) is a common gynecological malignancy, often diagnosed at an early stage with a high overall survival rate. Surgical treatment is the primary approach, guided by pathological and molecular characteristics. Stage IVB EC, characterized by intra and\/or extra-abdominal metastasis, presents a significant challenge with no clear consensus on optimal management. (2) Methods: A systematic literature review was conducted from January to May 2023, covering studies from 2000 to 2023. Eligible studies included retrospective case series, prospective trials, and randomized clinical trials. (3) Results: Of 116 studies identified, 21 were deemed relevant: 7 on primary surgery, 10 on neoadjuvant chemotherapy (NACT), and 4 on adjuvant treatment. Notably, the impact of residual tumor after primary surgery was a critical factor affecting survival. The use of NACT followed by interval debulking surgery showed promise, particularly in cases deemed unresectable. Adjuvant treatment, combining radiotherapy and chemotherapy, demonstrated improved survival but lacked consensus regarding its role. (4) Conclusions: Stage IVB EC poses a complex challenge with limited evidence to guide management. Optimal cytoreduction remains crucial, and NACT should be considered for unresectable cases. Multimodality adjuvant therapy may benefit patients, even with disease spread beyond the pelvis. Future advances in molecular classification and targeted therapies are expected to enhance treatment strategies.<\/jats:p>","DOI":"10.3390\/cancers15215123","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T11:34:47Z","timestamp":1698147287000},"page":"5123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Optimal Management for Stage IVB Endometrial Cancer: A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-5663","authenticated-orcid":false,"given":"Vito Andrea","family":"Capozzi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Scarpelli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-5424","authenticated-orcid":false,"given":"Alessandra","family":"De Finis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Rotondella","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Scebba","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asya","family":"Gallinelli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Montrucchio","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7881-1742","authenticated-orcid":false,"given":"Giulia","family":"Martignon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Leotta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tullio","family":"Ghi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2324-5409","authenticated-orcid":false,"given":"Roberto","family":"Berretta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1056\/NEJMoa0908806","article-title":"Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer","volume":"363","author":"Vergote","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1056\/NEJMra1514010","article-title":"Endometrial Cancer","volume":"383","author":"Lu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1136\/ijgc-2020-002230","article-title":"ESGO\/ESTRO\/ESP guidelines for the management of patients with endometrial carcinoma","volume":"31","author":"Concin","year":"2021","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1093\/annonc\/mdy058","article-title":"Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series","volume":"29","author":"Kommoss","year":"2018","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, and Levine, D.A. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497, 67\u201373. Erratum in Nature 2013, 500, 242.","DOI":"10.1038\/nature12113"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"RAINBO Research Consortium (2022). Refining adjuvant treatment in endometrial cancer based on molecular features: The RAINBO clinical trial program. Int. J. Gynecol. Cancer, 33, 109\u2013117.","DOI":"10.1136\/ijgc-2022-004039"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijgo.2009.02.010","article-title":"Revised FIGO staging for carcinoma of the endometrium","volume":"105","author":"Creasman","year":"2009","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/s10147-009-0878-3","article-title":"Analysis of stage IVB endometrial carcinoma patients with distant metastasis: A review of prognoses in 55 patients","volume":"14","author":"Numazaki","year":"2009","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1200\/JCO.19.00037","article-title":"Uterine Cancer: Adjuvant Therapy and Management of Metastatic Disease","volume":"37","author":"Creutzberg","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100887","DOI":"10.1016\/j.gore.2021.100887","article-title":"Neoadjuvant chemotherapy for advanced stage endometrial cancer: A systematic review","volume":"38","author":"Huang","year":"2021","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ygyno.2008.10.009","article-title":"Stage IVB endometrial cancer: Does applying an ovarian cancer treatment paradigm result in similar outcomes? A case-control analysis","volume":"112","author":"Landrum","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107125","DOI":"10.1016\/j.ijscr.2022.107125","article-title":"Complete resection after pembrolizumab treatment followed by salvage surgery in stage IVB endometrial cancer: A case report","volume":"94","author":"Taguchi","year":"2022","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Senguttuvan, R.N., Wei, C., Raoof, M., Dellinger, T.H., and Wang, E.W. (2023). Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma. J. Clin. Med., 12.","DOI":"10.3390\/jcm12113839"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jclinepi.2010.04.026","article-title":"GRADE guidelines: 1. Introduction\u2014GRADE evidence profiles and summary of findings tables","volume":"64","author":"Guyatt","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/gyno.2000.5843","article-title":"Stage IVB endometrial carcinoma: The role of cytoreductive surgery and determinants of survival","volume":"78","author":"Bristow","year":"2000","journal-title":"Gynecol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1136\/ijgc-00009577-200209000-00007","article-title":"The influence of cytoreductive surgery on survival and morbidity in stage IVB endometrial cancer","volume":"12","author":"Ayhan","year":"2002","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ygyno.2023.05.069","article-title":"The right time for change: A report on the heterogeneity of IVB endometrial cancer and improved risk-stratification provided by new 2023 FIGO staging criteria","volume":"175","author":"Haight","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ygyno.2013.10.035","article-title":"Clinical predictors of long-term survival for stage IVB uterine papillary serous carcinoma confined to the abdomen","volume":"132","author":"Lee","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.ygyno.2012.08.012","article-title":"Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: A retrospective multi-institutional analysis of 248 patients in Japan","volume":"127","author":"Eto","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1245\/s10434-009-0892-8","article-title":"Endometrial carcinoma with extra-abdominal metastasis: Improved prognosis following cytoreductive surgery","volume":"17","author":"Ueda","year":"2010","journal-title":"Ann. Surg. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0140-6736(14)62223-6","article-title":"Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): An open-label, randomised, controlled, non-inferiority trial","volume":"386","author":"Kehoe","year":"2015","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1136\/ijgc-2020-001640","article-title":"Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850)","volume":"30","author":"Fagotti","year":"2020","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1136\/ijgc-2019-000682","article-title":"TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33\/AGO-OVAR OP7)","volume":"29","author":"Reuss","year":"2019","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1136\/ijgc-00009577-200209000-00008","article-title":"FIGO stage III and IV uterine papillary serous carcinoma: Impact of residual disease on survival","volume":"12","author":"Memarzadeh","year":"2002","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s10147-022-02284-9","article-title":"JGOG2046: A feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer","volume":"28","author":"Nakanishi","year":"2023","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/sj.bjc.6605157","article-title":"Neoadjuvant chemotherapy followed by interval debulking surgery in patients with serous endometrial cancer with transperitoneal spread (stage IV): A new preferred treatment?","volume":"101","author":"Vandenput","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ygyno.2013.08.036","article-title":"Status of treatment for the overall population of patients with stage IVb endometrial cancer, and evaluation of the role of preoperative chemotherapy: A retrospective multi-institutional study of 426 patients in Japan","volume":"131","author":"Eto","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2204937","DOI":"10.1080\/01443615.2023.2204937","article-title":"Survival benefit of surgical treatment for patients with stage IVB endometrial cancer: A propensity score-matched SEER database analysis","volume":"43","author":"Zhang","year":"2023","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.3802\/jgo.2023.34.e77","article-title":"Efficacy of intra-abdominal cytoreductive surgery in advanced endometrial cancer with distant metastasis","volume":"34","author":"Kanno","year":"2023","journal-title":"J. Gynecol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e2028612","DOI":"10.1001\/jamanetworkopen.2020.28612","article-title":"Association of Neoadjuvant Chemotherapy with Overall Survival in Women with Metastatic Endometrial Cancer","volume":"3","author":"Tobias","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ygyno.2022.03.021","article-title":"Population-level uptake of neoadjuvant chemotherapy for stage IVB endometrial cancer","volume":"165","author":"Jooya","year":"2022","journal-title":"Gynecol. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/0300891618784785","article-title":"Neoadjuvant chemotherapy followed by interval debulking surgery for unresectable stage IVB Serous endometrial cancer","volume":"105","author":"Bogani","year":"2019","journal-title":"Tumori J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/IGC.0000000000000321","article-title":"Neoadjuvant chemotherapy versus primary cytoreductive surgery for stage IV uterine serous carcinoma","volume":"25","author":"Frolova","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2151355","DOI":"10.1080\/01443615.2022.2151355","article-title":"Neoadjuvant chemotherapy in patients with stage IVB uterine serous carcinoma: A Turkish multicentric study","volume":"43","author":"Unsal","year":"2023","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1136\/ijgc-2020-001822","article-title":"Adjuvant therapy for endometrial cancer in the era of molecular classification: Radiotherapy, chemoradiation and novel targets for therapy","volume":"31","author":"Horeweg","year":"2021","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S1470-2045(18)30079-2","article-title":"Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): Final results of an international, open-label, multicentre, randomised, phase 3 trial","volume":"19","author":"Powell","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1200\/JCO.20.00549","article-title":"Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit from Adjuvant Therapy","volume":"38","author":"Powell","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1056\/NEJMoa1813181","article-title":"Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer","volume":"380","author":"Matei","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1200\/JCO.20.01076","article-title":"Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology\/GOG0209)","volume":"38","author":"Miller","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_41","first-page":"226","article-title":"Stage IVB endometrial cancer confined to the abdomen: Is chemotherapy superior to radiotherapy?","volume":"37","author":"Cirik","year":"2016","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.ygyno.2022.04.007","article-title":"Does the addition of radiation improve survival compared to chemotherapy alone in women with stage IV endometrial carcinoma? Analysis of the NCDB and SEER databases","volume":"165","author":"Barrington","year":"2022","journal-title":"Gynecol. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"237.e1","DOI":"10.1016\/j.ajog.2021.04.254","article-title":"Primary cytoreductive surgery for advanced stage endometrial cancer: A systematic review and meta-analysis","volume":"225","author":"Albright","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/ijgo.14923","article-title":"FIGO staging of endometrial cancer: 2023","volume":"162","author":"Berek","year":"2023","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"217","DOI":"10.6004\/jnccn.2022.7254","article-title":"Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer","volume":"21","author":"Gordhandas","year":"2023","journal-title":"J. Natl. Compr. Cancer Netw."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/21\/5123\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:11:04Z","timestamp":1760130664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/21\/5123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":45,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["cancers15215123"],"URL":"https:\/\/doi.org\/10.3390\/cancers15215123","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,24]]}}}