Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB
Identifieur interne : 004201 ( Pmc/Corpus ); précédent : 004200; suivant : 004202Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB
Auteurs : Kyung Hee Han ; Hee Seung Kim ; Maria Lee ; Hyun Hoon Chung ; Yong Sang SongSource :
- Medicine [ 0025-7974 ] ; 2017.
Abstract
Risk grouping for treatment and follow-up strategy of early stage endometrial cancer is confusing to apply in clinical conditions. We investigated the stage-based prognostic factors for tumor recurrence in stage I endometrial cancer with endometrioid histology (EEC).
The medical records of women diagnosed with endometrial adenocarcinoma between 1993 and 2013 were retrospectively reviewed. In 521 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I EEC were included. The baseline patient characteristics were analyzed with the chi-square test and Fisher's exact tests. A multivariate analysis with a Cox proportional hazard model and logistic regression were performed to identify the prognostic factors for recurrence-free survival (RFS) in FIGO stage I EEC.
The median follow-up period for the included patients was 74.6 months (3.1–264.9 months). Tumor recurrence occurred in 30 patients (5.8%) with a median time span of 22.85 months (2.2–124.7 months). Only 2 factors among the conventional adverse risk factors, including myometrial invasion and histologic grade, affected tumor recurrence in stage I EEC (
Within stage I EEC, the prognostic factors for tumor recurrence were different between stages IA and IB. Myometrial invasion comprised the prognostic factor in stage IA, whereas the histologic grade comprised the prognostic factor in stage IB.
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DOI: 10.1097/MD.0000000000006976
PubMed: 28538399
PubMed Central: 5457879
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB</title><author><name sortKey="Han, Kyung Hee" sort="Han, Kyung Hee" uniqKey="Han K" first="Kyung Hee" last="Han">Kyung Hee Han</name><affiliation><nlm:aff id="aff1">Department of Obstetrics and Gynecology, Seoul National University Hospital Healthcare System Gangnam Center</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation></author><author><name sortKey="Kim, Hee Seung" sort="Kim, Hee Seung" uniqKey="Kim H" first="Hee Seung" last="Kim">Hee Seung Kim</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Cancer Research Institute, Seoul National University College of Medicine</nlm:aff></affiliation></author><author><name sortKey="Lee, Maria" sort="Lee, Maria" uniqKey="Lee M" first="Maria" last="Lee">Maria Lee</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation></author><author><name sortKey="Chung, Hyun Hoon" sort="Chung, Hyun Hoon" uniqKey="Chung H" first="Hyun Hoon" last="Chung">Hyun Hoon Chung</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation></author><author><name sortKey="Song, Yong Sang" sort="Song, Yong Sang" uniqKey="Song Y" first="Yong Sang" last="Song">Yong Sang Song</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Cancer Research Institute, Seoul National University College of Medicine</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Major in Biomodulation, World Class University, Seoul National University, Seoul, Republic of Korea.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28538399</idno><idno type="pmc">5457879</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457879</idno><idno type="RBID">PMC:5457879</idno><idno type="doi">10.1097/MD.0000000000006976</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">004201</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004201</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB</title><author><name sortKey="Han, Kyung Hee" sort="Han, Kyung Hee" uniqKey="Han K" first="Kyung Hee" last="Han">Kyung Hee Han</name><affiliation><nlm:aff id="aff1">Department of Obstetrics and Gynecology, Seoul National University Hospital Healthcare System Gangnam Center</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation></author><author><name sortKey="Kim, Hee Seung" sort="Kim, Hee Seung" uniqKey="Kim H" first="Hee Seung" last="Kim">Hee Seung Kim</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Cancer Research Institute, Seoul National University College of Medicine</nlm:aff></affiliation></author><author><name sortKey="Lee, Maria" sort="Lee, Maria" uniqKey="Lee M" first="Maria" last="Lee">Maria Lee</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation></author><author><name sortKey="Chung, Hyun Hoon" sort="Chung, Hyun Hoon" uniqKey="Chung H" first="Hyun Hoon" last="Chung">Hyun Hoon Chung</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation></author><author><name sortKey="Song, Yong Sang" sort="Song, Yong Sang" uniqKey="Song Y" first="Yong Sang" last="Song">Yong Sang Song</name><affiliation><nlm:aff id="aff2">Department of Obstetrics and Gynecology</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Cancer Research Institute, Seoul National University College of Medicine</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Major in Biomodulation, World Class University, Seoul National University, Seoul, Republic of Korea.</nlm:aff></affiliation></author></analytic><series><title level="j">Medicine</title><idno type="ISSN">0025-7974</idno><idno type="eISSN">1536-5964</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>Risk grouping for treatment and follow-up strategy of early stage endometrial cancer is confusing to apply in clinical conditions. We investigated the stage-based prognostic factors for tumor recurrence in stage I endometrial cancer with endometrioid histology (EEC).</p><p>The medical records of women diagnosed with endometrial adenocarcinoma between 1993 and 2013 were retrospectively reviewed. In 521 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I EEC were included. The baseline patient characteristics were analyzed with the chi-square test and Fisher's exact tests. A multivariate analysis with a Cox proportional hazard model and logistic regression were performed to identify the prognostic factors for recurrence-free survival (RFS) in FIGO stage I EEC.</p><p>The median follow-up period for the included patients was 74.6 months (3.1–264.9 months). Tumor recurrence occurred in 30 patients (5.8%) with a median time span of 22.85 months (2.2–124.7 months). Only 2 factors among the conventional adverse risk factors, including myometrial invasion and histologic grade, affected tumor recurrence in stage I EEC (<italic>P</italic> = .003 and <italic>P</italic> = .003, respectively). Myometrial invasion was an independent prognostic factor for RFS in stage IA EEC via multivariate analysis (<italic>P</italic> = .005). In stage IB EEC, the histologic grade was an independent prognostic factor for RFS. The median RFS of stage IB EEC was 156.0 months in grade 1, 120.0 months in grade 2, and 105.9 months in grade 3 (<italic>P</italic> = .006).</p><p>Within stage I EEC, the prognostic factors for tumor recurrence were different between stages IA and IB. Myometrial invasion comprised the prognostic factor in stage IA, whereas the histologic grade comprised the prognostic factor in stage IB.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Colombo, N" uniqKey="Colombo N">N Colombo</name></author><author><name sortKey="Preti, E" uniqKey="Preti E">E Preti</name></author><author><name sortKey="Landoni, F" uniqKey="Landoni F">F Landoni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vergote, I" uniqKey="Vergote I">I Vergote</name></author><author><name sortKey="Trope, Cg" uniqKey="Trope C">CG Trope</name></author><author><name sortKey="Amant, F" uniqKey="Amant F">F Amant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morice, P" uniqKey="Morice P">P Morice</name></author><author><name sortKey="Leary, A" uniqKey="Leary A">A Leary</name></author><author><name sortKey="Creutzberg, C" uniqKey="Creutzberg C">C Creutzberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pecorelli, S" uniqKey="Pecorelli S">S Pecorelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Creutzberg, Cl" uniqKey="Creutzberg C">CL Creutzberg</name></author><author><name sortKey="Van Putten, Wl" uniqKey="Van Putten W">WL van Putten</name></author><author><name sortKey="Koper, Pc" uniqKey="Koper P">PC Koper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Canlorbe, G" uniqKey="Canlorbe G">G Canlorbe</name></author><author><name sortKey="Bendifallah, S" uniqKey="Bendifallah S">S Bendifallah</name></author><author><name sortKey="Laas, E" uniqKey="Laas E">E Laas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Colombo, N" uniqKey="Colombo N">N Colombo</name></author><author><name sortKey="Creutzberg, C" uniqKey="Creutzberg C">C Creutzberg</name></author><author><name sortKey="Amant, F" uniqKey="Amant F">F Amant</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Creutzberg, Cl" uniqKey="Creutzberg C">CL Creutzberg</name></author><author><name sortKey="Van Putten, Wl" uniqKey="Van Putten W">WL van Putten</name></author><author><name sortKey="Warlam Rodenhuis, Cc" uniqKey="Warlam Rodenhuis C">CC Warlam-Rodenhuis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Keys, Hm" uniqKey="Keys H">HM Keys</name></author><author><name sortKey="Roberts, Ja" uniqKey="Roberts J">JA Roberts</name></author><author><name sortKey="Brunetto, Vl" uniqKey="Brunetto V">VL Brunetto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Jy" uniqKey="Lee J">JY Lee</name></author><author><name sortKey="Kim, K" uniqKey="Kim K">K Kim</name></author><author><name sortKey="Lee, Ts" uniqKey="Lee T">TS Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abu Rustum, Nr" uniqKey="Abu Rustum N">NR Abu-Rustum</name></author><author><name sortKey="Zhou, Q" uniqKey="Zhou Q">Q Zhou</name></author><author><name sortKey="Iasonos, A" uniqKey="Iasonos A">A Iasonos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wright, Jd" uniqKey="Wright J">JD Wright</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Burke, Wm" uniqKey="Burke W">WM Burke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benedetti Panici, P" uniqKey="Benedetti Panici P">P Benedetti Panici</name></author><author><name sortKey="Basile, S" uniqKey="Basile S">S Basile</name></author><author><name sortKey="Maneschi, F" uniqKey="Maneschi F">F Maneschi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bogani, G" uniqKey="Bogani G">G Bogani</name></author><author><name sortKey="Ditto, A" uniqKey="Ditto A">A Ditto</name></author><author><name sortKey="Martinelli, F" uniqKey="Martinelli F">F Martinelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Group, Aes" uniqKey="Group A">AES Group</name></author><author><name sortKey="Blake, P" uniqKey="Blake P">P Blake</name></author><author><name sortKey="Swart, Am" uniqKey="Swart A">AM Swart</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Medicine (Baltimore)</journal-id><journal-id journal-id-type="iso-abbrev">Medicine (Baltimore)</journal-id><journal-id journal-id-type="publisher-id">MEDI</journal-id><journal-title-group><journal-title>Medicine</journal-title></journal-title-group><issn pub-type="ppub">0025-7974</issn><issn pub-type="epub">1536-5964</issn><publisher><publisher-name>Wolters Kluwer Health</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28538399</article-id><article-id pub-id-type="pmc">5457879</article-id><article-id pub-id-type="publisher-id">MD-D-16-06439</article-id><article-id pub-id-type="doi">10.1097/MD.0000000000006976</article-id><article-id pub-id-type="art-access-id">06976</article-id><article-categories><subj-group subj-group-type="heading"><subject>5600</subject></subj-group><subj-group><subject>Research Article</subject><subject>Observational Study</subject></subj-group></article-categories><title-group><article-title>Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Han</surname><given-names>Kyung Hee</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Hee Seung</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Maria</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chung</surname><given-names>Hyun Hoon</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Yong Sang</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref rid="cor1" ref-type="corresp"><sup>∗</sup></xref></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Chatzistamatiou.</surname><given-names>Kimon</given-names></name></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Obstetrics and Gynecology, Seoul National University Hospital Healthcare System Gangnam Center</aff><aff id="aff2"><label>b</label>Department of Obstetrics and Gynecology</aff><aff id="aff3"><label>c</label>Cancer Research Institute, Seoul National University College of Medicine</aff><aff id="aff4"><label>d</label>Major in Biomodulation, World Class University, Seoul National University, Seoul, Republic of Korea.</aff><author-notes id="cor1"><corresp><label>∗</label>Correspondence: Yong Sang Song, Yong Sang Song, Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul 110-744, Republic of Korea (e-mail: <email>yssong@snu.ac.kr</email>).</corresp></author-notes><pub-date pub-type="collection"><month>5</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>26</day><month>5</month><year>2017</year></pub-date><volume>96</volume><issue>21</issue><elocation-id>e6976</elocation-id><history><date date-type="received"><day>24</day><month>10</month><year>2016</year></date><date date-type="rev-recd"><day>9</day><month>3</month><year>2017</year></date><date date-type="accepted"><day>28</day><month>4</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.</copyright-statement><copyright-year>2017</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0">http://creativecommons.org/licenses/by-nc-nd/4.0</ext-link></license-p></license></permissions><self-uri xlink:type="simple" xlink:href="medi-96-e6976.pdf"></self-uri><abstract><title>Abstract</title><p>Risk grouping for treatment and follow-up strategy of early stage endometrial cancer is confusing to apply in clinical conditions. We investigated the stage-based prognostic factors for tumor recurrence in stage I endometrial cancer with endometrioid histology (EEC).</p><p>The medical records of women diagnosed with endometrial adenocarcinoma between 1993 and 2013 were retrospectively reviewed. In 521 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I EEC were included. The baseline patient characteristics were analyzed with the chi-square test and Fisher's exact tests. A multivariate analysis with a Cox proportional hazard model and logistic regression were performed to identify the prognostic factors for recurrence-free survival (RFS) in FIGO stage I EEC.</p><p>The median follow-up period for the included patients was 74.6 months (3.1–264.9 months). Tumor recurrence occurred in 30 patients (5.8%) with a median time span of 22.85 months (2.2–124.7 months). Only 2 factors among the conventional adverse risk factors, including myometrial invasion and histologic grade, affected tumor recurrence in stage I EEC (<italic>P</italic> = .003 and <italic>P</italic> = .003, respectively). Myometrial invasion was an independent prognostic factor for RFS in stage IA EEC via multivariate analysis (<italic>P</italic> = .005). In stage IB EEC, the histologic grade was an independent prognostic factor for RFS. The median RFS of stage IB EEC was 156.0 months in grade 1, 120.0 months in grade 2, and 105.9 months in grade 3 (<italic>P</italic> = .006).</p><p>Within stage I EEC, the prognostic factors for tumor recurrence were different between stages IA and IB. Myometrial invasion comprised the prognostic factor in stage IA, whereas the histologic grade comprised the prognostic factor in stage IB.</p></abstract><kwd-group><title>Keywords</title><kwd>endometrial neoplasms</kwd><kwd>endometrioid carcinoma</kwd><kwd>prognosis</kwd><kwd>recurrence</kwd><kwd>survival</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>OPEN-ACCESS</meta-name><meta-value>TRUE</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec><label>1</label><title>Introduction</title><p>Endometrial cancer is the fifth most common female cancer in western counties, and its incidence has doubled in a decade until 2013 in Korea, from 4.5 to 8.8 per 100,000.<sup>[<xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref>]</sup> Most endometrial cancers comprise endometrioid endometrial cancer (EEC), especially in the early stage.<sup>[<xref rid="R3" ref-type="bibr">3</xref>]</sup> Many previous studies have reported the survival of endometrial cancer; however, few studies have addressed the pure endometrioid histology in the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer.</p><p>In previous reports, early stage endometrial cancer has typically been divided into low, intermediate, and high risk groups. However, these risk grouping did not implicate the staging system.<sup>[<xref rid="R4" ref-type="bibr">4</xref>]</sup> Although the FIGO system presents the tumor extent of early stage endometrial cancer, risk groups were classified using many possible factors that affect survival. Moreover, there was noticeable disparity in the criteria used for allocating patients into 3 risk groups among studies. Each study has applied its own criteria for risk group regarding patient age, histologic grade, myometrial invasion, and lymphovascular space invasion (LVSI).<sup>[<xref rid="R3" ref-type="bibr">3</xref>,<xref rid="R5" ref-type="bibr">5</xref>,<xref rid="R6" ref-type="bibr">6</xref>]</sup> Although many clinical trials tried to establish the evidence for adjuvant therapy in early stage endometrial cancer, there is yet a controversy whether to add adjuvant chemotherapy and/or adjuvant radiation therapy to the staging operation or not.<sup>[<xref rid="R7" ref-type="bibr">7</xref>]</sup></p><p>The European Society for Medical Oncology-European Society of Gynaecological Oncology-European Society of Radiotherapy and Oncology guideline or the National Comprehensive Cancer Network guideline presents various options for adjuvant treatment in FIGO stage I EEC according to myometrial invasion, histologic grade, and adverse risk factors including age, LVSI, tumor size, and lower uterine segment or surface cervical glandular involvement.<sup>[<xref rid="R8" ref-type="bibr">8</xref>]</sup> However, there is limited evidence for the number and weight of these adverse risk factors.</p><p>To minimize confusion in clinical applications for postoperative treatment and to determine a staging-based simple guideline, we investigated the prognostic factors for tumor recurrence in stage I EEC.</p></sec><sec><label>2</label><title>Methods</title><sec><label>2.1</label><title>Patients</title><p>We retrospectively reviewed the medical records of patients diagnosed with endometrial cancer at Seoul National University Hospital between 1993 and 2013 following Institutional Review Board approval. Women who had fatal comorbidity to affect survival, took hormone therapy for fertility sparing without surgery, or were diagnosed with uterine sarcoma were excluded. Of the 705 patients who undertook operation including total hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer, 551 patients were stage I. Finally, 521 patients with pathologically proven endometrioid histology in stage I endometrial cancer were included. Pelvic or para-aortic lymph node dissection was omitted when there was no preoperative evidence of lymph node metastasis in serum CA 125 level and imaging test such as computed tomography or magnetic resonance imaging. When there were lymph nodes highly suspicious of metastasis on preoperative imaging studies, they were evaluated during operation. Adjuvant therapy was selected from brachytherapy, external-beam radiation therapy, chemotherapy, or concurrent chemoradiation based on the known risk factors by a gynecologic oncologist. Tumor recurrence was confirmed via clinical pelvic exam or imaging study during regular check-up or following the occurrence of symptoms, such as vaginal spotting or abdominal discomfort.</p></sec><sec><label>2.2</label><title>Statistical analysis</title><p>Clinical and pathologic characteristics were analyzed with Student's <italic>t</italic> test, chi-square test, or Fisher's exact test. To calculate the survival function as a hazard ratio (HR) and confidence interval (CI), we used univariate and multivariate Cox's proportional hazard models and the Kaplan–Meier method with the log-rank test. The recurrence-free survival (RFS) indicates the time from diagnosis date to recurrence or the last follow-up date without recurrence. Statistical analyses were performed with SPSS 21 software (SPSS, Inc., Chicago, IL). A <italic>P</italic>-value less than .05 was considered statistically significant.</p></sec></sec><sec><label>3</label><title>Results</title><sec><label>3.1</label><title>Patients’ characteristics</title><p>The median age of the patients with stage I EEC was 52 years (19–84 years). The patient numbers in the age group less than 52 years were 255 in stage IA EEC and 15 in stage IB EEC (59.3% and 16.5%, respectively, <italic>P</italic> < .001). The known adverse risk factors were different between stages IA EEC and IB EEC (Table <xref ref-type="table" rid="T1">1</xref>). More patients in stage IB EEC had at least 1 of the adverse risk factors, such as high histologic grade, large tumor size, positive LVSI, and positive lower uterine segment involvement or surface cervical glandular involvement, than patients in stage IA EEC (95.6% vs 55.7%; <italic>P</italic> < .001). Lymph node dissection was not related to sub-classification within stage I EEC (<italic>P</italic> = .64).</p><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Clinical and pathologic characteristics of FIGO stage I endometrioid endometrial cancer.</p></caption><graphic xlink:href="medi-96-e6976-g001"></graphic></table-wrap></sec><sec><label>3.2</label><title>Recurrence</title><p>The median follow-up period was 74.6 months (3.1–264.9 months), and 30 patients exhibited tumor recurrence in stage I EEC (5.7%). Of the recurrent cases, the median interval period between diagnosis and tumor recurrence was 22.9 months (2.2–124.7 months). Over 5 years after diagnosis, 4 patients experienced tumor recurrence (14.7%). In our study, they had no common characteristics with the exception of positive myometrial invasion. The presence or number of adverse risk factors including LVSI was not associated with tumor recurrence in stage I EEC (<italic>P</italic> = .44 or <italic>P</italic> = .25, respectively). The presence or absence of adjuvant therapy had no significant effect on tumor recurrence (<italic>P</italic> = .17). In addition, the method of adjuvant treatment was not a risk factor for tumor recurrence in stage I EEC (<italic>P</italic> = .21).</p><p>Recurrence that occurred in the pelvic lymph node, paraaortic lymph node, vagina, adnexa, or pelvic serosa was defined as locoregional recurrence, whereas distant metastasis included inguinal lymph node, intraperitoneal disease, lung, liver, and bone. The patients with stage IB exhibited a tendency for distant metastasis; however, the difference in the recurrence site between stages IA and IB was not significant (<italic>P</italic> = .06). Adjuvant therapy was not associated with the recurrence site in stages IA and IB (<italic>P</italic> = .37 and <italic>P</italic> = .45, respectively).</p><p>Two factors, myometrial invasion and histologic grade, were associated with tumor recurrence in stage I EEC (<italic>P</italic> < .001 and <italic>P</italic> = .01, respectively). The multivariate logistic regression analysis indicated the risk factors for tumor recurrence, including myometrial invasion in stage IA EEC (<italic>P</italic> = .003) and histologic grade in stage IB EEC (<italic>P</italic> = .02). LVSI was not associated with tumor recurrence in the multivariate analysis in stages IA or IB EEC (<italic>P</italic> = .83 and <italic>P</italic> = .19, respectively).</p></sec><sec><label>3.3</label><title>Predictors of survival</title><p>In the overall stage I EEC, myometrial invasion and histologic grade were prognostic factors for tumor recurrence in the multivariate analysis with Cox's proportional hazard model (<italic>P</italic> = .003 and <italic>P</italic> = .003, respectively, Table <xref ref-type="table" rid="T2">2</xref>). LVSI exhibited a tendency to connect with RFS using the univariate analysis (<italic>P</italic> = .05). However, none of the conventional adverse risk factors including LVSI were associated with RFS using the multivariate analysis.</p><table-wrap id="T2" position="float"><label>Table 2</label><caption><p>Cox's proportional hazard models for prognostic factors of FIGO stage I endometrioid endometrial cancer.</p></caption><graphic xlink:href="medi-96-e6976-g002"></graphic></table-wrap><p>Figure <xref ref-type="fig" rid="F1">1</xref> indicates the RFS of stage IA EEC according to myometrial invasion using the Kaplan–Meier method with the log rank test (<italic>P</italic> = .002). In stage IA EEC, 10 years of RFS occurred in 99% of the cases without myometrial invasion and 89% of the cases with less than half of myometrial invasion. In stage IA EEC, multivariate analysis demonstrated that no myometrial invasion prolonged RFS compared with less than half myometrial invasion (<italic>P</italic> = .01, Table <xref ref-type="table" rid="T3">3</xref>).</p><fig id="F1" position="float"><label>Figure 1</label><caption><p>Kaplan–Meier curves of recurrence-free survival according to myometrial invasion in FIGO stage IA endometrioid endometrial cancer. Solid line: no myometrial invasion; dot line: under half of myometrial invasion. FIGO = International Federation of Gynecology and Obstetrics.</p></caption><graphic xlink:href="medi-96-e6976-g003"></graphic></fig><table-wrap id="T3" position="float"><label>Table 3</label><caption><p>Cox's proportional hazard models for prognostic factors in FIGO stage IA endometrioid endometrial cancer.</p></caption><graphic xlink:href="medi-96-e6976-g004"></graphic></table-wrap><p>Figure <xref ref-type="fig" rid="F2">2</xref> indicates the RFS of stage IB EEC by histologic grade. The 5-year RFS of the patients with stage IB EEC was 94% in grade 1, 79% in grade 2, and 74% in grade 3 (<italic>P</italic> = .01). Of the patients with stage IB EEC, the histologic grade was the only prognostic factor of recurrence using multivariate analysis (<italic>P</italic> = .01, Table <xref ref-type="table" rid="T4">4</xref>).</p><fig id="F2" position="float"><label>Figure 2</label><caption><p>Kaplan–Meier curves of recurrence-free survival according to histologic grade in FIGO stage IB endometrioid endometrial cancer. Solid line: grade 2; narrow dot line: grade 2; wide dot line: grade 3. FIGO = International Federation of Gynecology and Obstetrics.</p></caption><graphic xlink:href="medi-96-e6976-g005"></graphic></fig><table-wrap id="T4" position="float"><label>Table 4</label><caption><p>Cox's proportional hazard models for prognostic factors of FIGO stage IB endometrioid endometrial cancer.</p></caption><graphic xlink:href="medi-96-e6976-g006"></graphic></table-wrap></sec></sec><sec><label>4</label><title>Discussion</title><p>The application of additional treatment, including adjuvant radiation, chemotherapy, or observation, followed by surgery has been a controversial issue in early stage endometrial cancer.<sup>[<xref rid="R9" ref-type="bibr">9</xref>,<xref rid="R10" ref-type="bibr">10</xref>]</sup> Current management guidelines have defined risk groups based on myometrial invasion, histologic grade, and LVSI. In addition, alleged adverse risk factors, including age, positive LVSI, large tumor size, and positive lower uterine segment or surface cervical glandular involvement, have been used to guide decisions regarding adjuvant therapy.</p><p>There was no uniformed criteria for classification among studies which suggested risk group in early stage endometrial cancer.<sup>[<xref rid="R7" ref-type="bibr">7</xref>]</sup> Moreover, a sorting system based on various factors may also induce confusion during disease management in clinical settings, because it did not correspond to FIGO staging. The individual preferences of gynecologic oncologists might affect the method of adjuvant therapy and the long-term plan, resulting in a different management in the same clinical condition.<sup>[<xref rid="R11" ref-type="bibr">11</xref>]</sup> Simple guidelines based on the staging system may help facilitate clear decision.</p><p>We followed patients over time for up to 10 years to evaluate the prognostic factors of stage I EEC. Only 2 factors, myometrial invasion and histologic grade, affected tumor recurrence in stage I EEC. The prognostic factors were different between stages IA and IB within stage I EEC. Our data demonstrated that myometrial invasion comprised the significant prognostic factor of stage IA EEC similar to the 1988 FIGO staging. The revised 2010 FIGO system, which covers the overall histology type of endometrial cancers, merged cases with no myometrial invasion and cases with less than half of myometrial invasion in stage IA. Studies that supported the previous system have reported the results from patients with endometrioid histology.<sup>[<xref rid="R12" ref-type="bibr">12</xref>]</sup> In stage IB EEC, which included more than half of myometrial invasion, the histologic grade comprised the prognostic factor of tumor recurrence. The presence, number, or type of alleged adverse risk factors did not significantly affect the RFS in our study. Our data suggested that the primary factor to predict tumor survival in stage IB EEC was the histologic grade.</p><p>Some studies have indicated that lymphadenectomy influenced survival during the early stage of endometrial cancer.<sup>[<xref rid="R13" ref-type="bibr">13</xref>]</sup> However, a randomized trial determined that systematic pelvic lymphadenectomy of the early stage endometrial cancer only facilitated surgical staging, and it did not prolong survival.<sup>[<xref rid="R14" ref-type="bibr">14</xref>]</sup> Sentinel lymph node mapping and selective lymphadenectomy during the early stage of endometrial cancer comprised an effort to achieve a survival benefit and decrease adverse effects, such as lymphedema or delayed postoperative recovery.<sup>[<xref rid="R15" ref-type="bibr">15</xref>]</sup> In our study, whether pelvic or para-aortic lymph node dissection were performed or not had no effect on RFS of patients with stage I EEC.</p><p>A previous study reported that adjuvant therapy did not affect tumor survival in early stage endometrial cancer.<sup>[<xref rid="R16" ref-type="bibr">16</xref>]</sup> Adjuvant chemotherapy was performed on patients with intermediate to high risk stage I endometrial cancer. However, our multivariate analyses found that the application of adjuvant chemotherapy itself or its regimen was not associated with the rate of tumor recurrence of stage I EEC.</p><p>Although we investigated FIGO stage-specific prognostic factors of stage I EEC, this study had some limitations. Retrospective design of the current study might induce selection bias to include patients with stage I EEC. In addition, there were not sufficient death events to analyze overall survival or cancer-specific survival. Prospective evaluation with long-term follow-up is needed to draw the accurate conclusion.</p><p>There were no standard criteria of risk grouping in early stage endometrial cancer, and the methods stated in the previous reports were too complicated to be applied in clinical practice. Prognostic factors based on the FIGO stage would make it convenient for gynecologic oncologist to assess tumor prognosis and select appropriate postoperative management. Additional investigations regarding adjuvant treatment and follow-up according to the staging system would properly guide gynecologic oncologists without broad variation.</p></sec></body><back><fn-group><fn fn-type="abbr"><p>Abbreviations: CI = confidence interval, EEC = endometrial cancer with endometrioid histology, FIGO = International Federation of Gynecology and Obstetrics, HR = hazard ratio, LVSI = lymphovascular space invasion, RFS = recurrence-free survival.</p></fn><fn fn-type="COI-statement"><p> The authors have no funding and conflicts of interest to disclose.</p></fn></fn-group><ref-list><title>References</title><ref id="R1"><label>[1]</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Colombo</surname><given-names>N</given-names></name><name><surname>Preti</surname><given-names>E</given-names></name><name><surname>Landoni</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up</article-title>. <source>Ann Oncol</source><year>2013</year>;<volume>24</volume><issue>(suppl 6)</issue>:<fpage>vi33</fpage>–<lpage>8</lpage>.<pub-id pub-id-type="pmid">24078661</pub-id></mixed-citation></ref><ref id="R2"><label>[2]</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vergote</surname><given-names>I</given-names></name><name><surname>Trope</surname><given-names>CG</given-names></name><name><surname>Amant</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer</article-title>. <source>N Engl J Med</source><year>2010</year>;<volume>363</volume>:<fpage>943</fpage>–<lpage>53</lpage>.<pub-id pub-id-type="pmid">20818904</pub-id></mixed-citation></ref><ref id="R3"><label>[3]</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Morice</surname><given-names>P</given-names></name><name><surname>Leary</surname><given-names>A</given-names></name><name><surname>Creutzberg</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Endometrial cancer</article-title>. <source>Lancet</source><year>2016</year>;<volume>387</volume>:<fpage>1094</fpage>–<lpage>108</lpage>.<pub-id pub-id-type="pmid">26354523</pub-id></mixed-citation></ref><ref id="R4"><label>[4]</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pecorelli</surname><given-names>S</given-names></name></person-group><article-title>Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium</article-title>. <source>Int J Gynaecol Obstet</source><year>2009</year>;<volume>105</volume>:<fpage>103</fpage>–<lpage>4</lpage>.<pub-id pub-id-type="pmid">19367689</pub-id></mixed-citation></ref><ref id="R5"><label>[5]</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Creutzberg</surname><given-names>CL</given-names></name><name><surname>van Putten</surname><given-names>WL</given-names></name><name><surname>Koper</surname><given-names>PC</given-names></name><etal></etal></person-group><article-title>Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. 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