Article Text

Download PDFPDF
Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer
  1. Eric Rios-Doria1,
  2. Nadeem R Abu-Rustum1,2,
  3. Kaled M Alektiar3,
  4. Vicky Makker4,5,
  5. Ying L Liu4,5,
  6. Dmitriy Zamarin4,5,
  7. Claire F Friedman4,5,
  8. Carol Aghajanian4,5,
  9. Lora H Ellenson6,
  10. Sarah Chiang6,
  11. Britta Weigelt6,
  12. Jennifer J Mueller1,2 and
  13. Mario M Leitao1,2
    1. 1Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    2. 2Department of OB/GYN, Weill Cornell Medical College, New York, New York, USA
    3. 3Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    4. 4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    5. 5Department of Medicine, Weill Cornell Medical College, New York, New York, USA
    6. 6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    1. Correspondence to Dr Mario M Leitao, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA; leitaom{at}mskcc.org

    Abstract

    Objective We assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease.

    Methods Patients diagnosed with stage IA, IB, or II endometrioid endometrial cancer and primary surgical management were identified from January 1, 2007 to December 31, 2019. All SLNs underwent ultrastaging according to the institutional protocol. Patients with cytokeratin positive cells, micrometastases, and macrometastases were excluded. Clinical, pathology, and molecular subtype data were reviewed.

    Results Overall, 1214 patients with early stage endometrioid endometrial cancer met the inclusion criteria, of whom 1089 (90%) had node negative disease and 125 (10%) had isolated tumor cells. Compared with node negative disease, the presence of isolated tumor cells had a greater association with deep myometrial invasion, lymphovascular space invasion, receipt of adjuvant therapy, and adjuvant chemotherapy with or without radiation (p<0.01). There was no significant difference in survival rates between patients with isolated tumor cells and node negative disease (3 year progression free survival rate 94% vs 91%, respectively, p=0.21; 3 year overall survival rate 98% vs 96%, respectively, p=0.45). Progression free survival did not significantly differ among patients with isolated tumor cells who received no adjuvant therapy or chemotherapy with or without radiation (p=0.31). There was no difference in the distribution of molecular subtypes between patients with isolated tumor cells (n=28) and node negative disease (n=194; p=0.26). Three year overall survival rates differed significantly when stratifying the entire cohort by molecular subtype (p=0.04).

    Conclusions Patients with isolated tumor cells demonstrated less favorable uterine pathologic features and received more adjuvant treatment with similar survival compared with patients with nodenegative disease. Among the available data, molecular classification did not have a significant association with the presence of isolated tumor cells, although copy number-high status was a poor prognostic indicator in early stage endometrioid endometrial cancer.

    • Endometrial Neoplasms
    • Uterine Cancer

    Data availability statement

    Data are available upon reasonable request. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

    Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data are available upon reasonable request. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

    View Full Text

    Footnotes

    • X @RiosDoriaMD, @leitaomd

    • Contributors ER-D: conceptualization, data curation, formal analysis, methodology, and writing–review and editing. NRA-R, KA, VM, YLL, DZ, CFF, CAA, LE, SC, and BW: writing–review and editing. JM: conceptualization, data curation, formal analysis, methodology, writing–original draft, and writing–review and editing. ML: conceptualization, formal analysis, methodology, and writing–review and editing, guarantor.

    • Funding Research reported in this publication was supported in part by a National Institutes of Health (NIH)/National Cancer Institute (NCI) Cancer Center Support Grant (P30 CA008748). BW is supported in part by Cycle for Survival, NIH/NCI (P50 CA247749), and Breast Cancer Research Foundation grants.

    • Competing interests BW reports research support by Repare Therapeutics, outside of the current work. CAA reports clinical trial funding paid to the institution from AstraZeneca; funding paid to the institution from BMS and SELLAS Life Sciences Group; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). DZ reports institutional grants from Genentech, AstraZeneca, BMS, SELLAS Life Sciences Group, and Plexxikon; personal fees from Genentech, AstraZeneca, Xencor, Memgen, Synthekine, Celldex, and Hookipa; and stock options from Immunos, Accurius, Mana Therapeutics, and Calidi Biotherapeutics, outside of the submitted work. DZ is also an inventor on a patent related to the use of oncolytic Newcastle disease virus for cancer therapy. YLL reports research funding from AstraZeneca, GSK, and Repare Therapeutics. NRA-R reports research funding paid to the institution from GRAIL. ML reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, and advisory board participation for JnJ/Ethicon and Takeda. VM reports advisory board participation (unpaid) for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. CFF reports participation in the scientific advisory boards for Merck (LYNK-002) and Genentech (MyPathway) without compensation, consulting for Seagen and Bristol Myers Squibb, and institutional research funds from Genentech/Roche, Bristol Myers Squibb, Merck, AstraZeneca, and Daiichi. SC serves as a consultant for AstraZeneca.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.