{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:44:20Z","timestamp":1793724260130,"version":"4.6.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr. Treat. Options in Oncol."],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Opinion Statement<\/jats:title><jats:p>The standard of treatment for node-positive endometrial cancer (FIGO Stage IIIC) in North America has been systemic therapy with or without additional external beam radiation therapy (RT) given as pelvic or extended field RT. However, this treatment paradigm is rapidly evolving with improvements in systemic chemotherapy, the emergence of targeted therapies, and improved molecular characterization of these tumors. The biggest question facing providers regarding management of stage IIIC endometrial cancer at this time is: what is the best management strategy to use with regard to combinations of cytotoxic chemotherapy, immunotherapy, other targeted therapeutics, and radiation that will maximize clinical benefit and minimize toxicities for the best patient outcomes? While clinicians await the results of ongoing clinical trials regarding combined immunotherapy\/RT as well as management based on molecular classification, we must make decisions regarding the best treatment combinations for our patients. Based on the available literature, we are offering stage IIIC patients without measurable disease postoperatively both adjuvant chemotherapy and IMRT with carboplatin, paclitaxel, and with or without pembrolizumab\/dostarlimab as primary adjuvant therapy. Patients with measurable disease post operatively, high risk histologies, or stage IV disease receive chemoimmunotherapy, and vaginal brachytherapy is added for those with uterine risk factors for vaginal recurrence. In the setting of endometrioid EC recurrence more than 6\u00a0months after treatment, patients with pelvic nodal and vaginal recurrence are offered IMRT and brachytherapy without chemotherapy. For measurable recurrence not suitable for pelvic radiation alone, chemoimmunotherapy is preferred as standard of care.<\/jats:p>","DOI":"10.1007\/s11864-023-01169-x","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T08:02:19Z","timestamp":1706169739000},"page":"330-345","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Treatment of node-positive endometrial cancer: chemotherapy, radiation, immunotherapy, and targeted therapy"],"prefix":"10.1007","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-5221","authenticated-orcid":false,"given":"Elizabeth A.","family":"Tubridy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil K.","family":"Taunk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"issue":"1","key":"1169_CR1","first-page":"7","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel RL, et al. 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Lancet Oncol. 2017;18(3):384\u201392.","journal-title":"Lancet Oncol"},{"issue":"2","key":"1169_CR8","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.ygyno.2017.05.024","volume":"146","author":"M Plante","year":"2017","unstructured":"Plante M, et al. Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: does adjuvant treatment matter? Gynecol Oncol. 2017;146(2):240\u20136.","journal-title":"Gynecol Oncol"},{"issue":"1","key":"1169_CR9","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1200\/JCO.2004.00.7617","volume":"24","author":"ME Randall","year":"2006","unstructured":"Randall ME, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. 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This important RCT compared radiation alone to chemoRT in high-intermediate and high risk EC subjects and found that chemoRT improved OS in stage III subjects and in allcomers improved FFS but not OS.","journal-title":"The Lancet Oncology"},{"issue":"29","key":"1169_CR13","doi-asserted-by":"publisher","first-page":"3388","DOI":"10.1200\/JCO.20.00549","volume":"38","author":"A Le\u00f3n-Castillo","year":"2020","unstructured":"\u2022\u2022 Le\u00f3n-Castillo A, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. Journal of Clinical Oncology. 2020;38(29):3388\u201397. This paper is of major significance because it identified four moleculear subgroups in EC (p53abn, MRRd, NSMP, POLEmut) with clinically important differences in RFS and response to chemotherapy and chemoRT. 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Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability\/mismatch repair\u2013deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1\u201310.","journal-title":"J Clin Oncol"},{"key":"1169_CR20","doi-asserted-by":"publisher","unstructured":"Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient\/microsatellite instability-high (dMMR\/MSI-H) or proficient\/stable (MMRp\/MSS) endometrial cancer: Interim results from GARNET - A phase I, single-arm study. J ImmunoTher Cancer. 2022;10(1). https:\/\/doi.org\/10.1136\/jitc-2021-003777","DOI":"10.1136\/jitc-2021-003777"},{"issue":"23","key":"1169_CR21","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1056\/NEJMoa2216334","volume":"388","author":"MR Mirza","year":"2023","unstructured":"\u2022\u2022 Mirza MR, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. New England Journal of Medicine. 2023;388(23):2145\u201358. This study, also known as RUBY, is a practice changing Phase III RCT comparing standard of care chemotherapy with immunotherapy (dostarlimab) to chemotherapy alone in advanced EC with marked improvement in PFS, particularly in the MMRd population.","journal-title":"New England Journal of Medicine"},{"issue":"23","key":"1169_CR22","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1056\/NEJMoa2302312","volume":"388","author":"RN Eskander","year":"2023","unstructured":"\u2022\u2022 Eskander RN, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159\u201370. 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