Molecular classification in fertility-sparing treatment of early-stage endometrial cancer: A potential tool for optimizing patient selection.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0365304 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-6859 (Electronic) Linking ISSN: 00908258 NLM ISO Abbreviation: Gynecol Oncol Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Endometrial Neoplasms*/pathology ; Endometrial Neoplasms*/classification ; Endometrial Neoplasms*/therapy ; Endometrial Neoplasms*/genetics ; Fertility Preservation*/methods ; Patient Selection* ; Neoplasm Staging*; Humans ; Female ; Adult ; Middle Aged ; Tumor Suppressor Protein p53/genetics ; Poly-ADP-Ribose Binding Proteins/genetics ; Retrospective Studies ; DNA Polymerase II/genetics
    • Abstract:
      Objective: To investigate the prognostic significance of molecular classification on treatment outcomes of fertility-sparing treatment (FST) in early-stage endometrial cancer (EC), and its potential in optimizing fertility-sparing management.
      Methods: Patients with early-stage EC who received FST with ProMisE classification were investigated. Oncological and reproductive outcomes were compared across four molecular subtypes. Factors influencing complete response (CR) were analyzed.
      Results: Among 116 molecularly classified patients, 80 were evaluated for therapeutic effects, including 64 (80.0 %) p53wt, 7 (8.7 %) MMR-D, 5 (6.3 %) POLE EDM, and 4 (5.0 %) p53abn. Overall CR rates were comparable across four molecular subtypes, with 92.2 % of p53wt, 71.4 % of MMR-D, 100.0 % of POLE EDM, and 75.0 % of p53abn (P = 0.145). MMR-D patients needed the longest median treatment time to achieve CR (7.9 months, range 3.5-15.9), while POLE EDM required the shortest (3.0 months, range 2.8-6.4), followed by p53abn (3.5 months, range 3.0-3.7) and p53wt (3.7 months, range 2.2-22.8) (P = 0.049). Among 14 p53wt patients with superficial myometrial invasion (MI) or G2 histology, 13 (92.9 %) achieved CR, and of 8 who attempted to conceive,4 delivered. Multivariable analysis identified MMR-D, superficial MI and insulin resistance negatively predicted CR, while POLE EDM was a positive factor.
      Conclusions: Molecular classification of EC may serve as a tool for predicting response to FST and assist in identifying candidates for FST. POLE EDM patients tended to obtain promising outcomes. MMR-D cases should be cautiously administrated for FST with close surveillance. Patients with p53wt demonstrated favorable outcomes, including those with superficial MI or G2 EC. Patients with endometrium-confined p53abn tumors may benefit from FST. However, given the small sample sizes of certain subtypes, further investigation is necessary to validate these findings.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Endometrial cancer; Fertility-sparing treatment; Molecular classification; Progestin
    • Accession Number:
      0 (Tumor Suppressor Protein p53)
      0 (Poly-ADP-Ribose Binding Proteins)
      0 (TP53 protein, human)
      EC 2.7.7.7 (DNA Polymerase II)
      EC 2.7.7.7 (POLE protein, human)
    • Publication Date:
      Date Created: 20241026 Date Completed: 20241212 Latest Revision: 20241212
    • Publication Date:
      20241213
    • Accession Number:
      10.1016/j.ygyno.2024.10.012
    • Accession Number:
      39461269