{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:32:02Z","timestamp":1786437122778,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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>Objective: Fertility-preserving therapies are a potential option for selected patients with early-stage endometrial cancer and atypical endometrial hyperplasia\/endometrial intraepithelial neoplasia. This systematic review aims to evaluate the impact of fertility-preserving strategies according to molecular subtype. Methods: A comprehensive search was conducted in PubMed, Cochrane Library, EMBASE, and Web of Science for English-language studies published until June 2024, investigating fertility-sparing treatments using endocrine therapy in early-stage endometrial cancer, considering molecular classification. The PRISMA checklist was followed, and the protocol was registered in PROSPERO (CRD42025649342). Data on body mass index (BMI), age, and molecular classification (POLE-mutant, non-specific molecular profile [NSMP], p53-abnormal, and mismatch repair deficient [dMMR]) were extracted. The study assessed objective response rates (ORR), pregnancy outcomes, and survival outcomes. Statistical analyses were performed using R software. Results: The search identified 941 articles, and 10 studies with 457 patients were selected for final analysis. Pregnancy outcomes were reported in three studies, whilst all reported ORR data. Baseline median age (dMMR 35 years, POLE-mutant 38.2 years, p53-abnormal 33.9 years, and NSMP 31.6 years) and BMI (dMMR 24.3, POLE-mutant 27.9, p53-abnormal 26.2, and NSMP 29.8) differed by molecular subtype. Aggregated full-term delivery rates from the three studies reporting pregnancy outcomes were 36.4% (4\/11) for POLE-mutant, 22.1% (27\/122) for NSMP, 14.3% (1\/7) for p53-abnormal, and 4.0% (1\/25) for dMMR tumours, but statistical comparison was not feasible due to small sample size. Overall response rate was highest in NSMP (87.4%) and POLE-mutant tumours (84.6%), while dMMR (59.3%) and p53-abnormal (58.8%) had significantly lower ORR (compared to NSMP, p &lt; 0.001 and p = 0.03, respectively). Conclusions: These findings support the potential role of molecular classification in refining patient selection for fertility-sparing treatment in early-stage endometrial cancer. Pregnancy-related outcomes should be interpreted with caution given the limited available evidence.<\/jats:p>","DOI":"10.3390\/cancers18152439","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"2439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Profiling to Guide Fertility Sparing Therapy in Early-Stage Endometrial Cancer: A EORTC Gynaecological Cancer Group Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Ramon","family":"Yarza","sequence":"first","affiliation":[{"name":"Drug Development and Phase I Unit, START-CIOCC, University Hospital HM Sanchinarro, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3563-1825","authenticated-orcid":false,"given":"Reyes","family":"Oliver-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Gynaecologic Oncology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"},{"name":"School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2141-8313","authenticated-orcid":false,"given":"Eva","family":"Oldenburger","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7576-8565","authenticated-orcid":false,"given":"Lawrence","family":"Kasherman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Illawarra Cancer Care Centre, Wollongong, NSW 2500, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3707-1107","authenticated-orcid":false,"given":"Shira","family":"Peleg Hasson","sequence":"additional","affiliation":[{"name":"Oncology Department, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1767-586X","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Estrada-Lorenzo","sequence":"additional","affiliation":[{"name":"Library and Information Services, Hospital Universitario del Sureste, 28500 Arganda del Rey, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"\u00c1lvarez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, HM CIOCC Centro Integral Oncol\u00f3gico Clara Campal, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Martinez de Lara","sequence":"additional","affiliation":[{"name":"Drug Development and Phase I Unit, START-CIOCC, University Hospital HM Sanchinarro, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-0472","authenticated-orcid":false,"given":"Fernanda","family":"Herrera","sequence":"additional","affiliation":[{"name":"Radiation Oncology Service, Department of Oncology, Lausanne University Hospital, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-1903","authenticated-orcid":false,"given":"Judith","family":"Kroep","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Leiden University Medical Center, 2333 Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7166-9762","authenticated-orcid":false,"given":"Ainhoa","family":"Madariaga","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, 12 de Octubre University Hospital, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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