Criticisms Conservative treatment of EC Limited amount of data Retrospective studies in most cases Often short follow-up Insufficient information on reproductive outcome Lack of pretreatment fertility counseling Prospective, multicentre registry study to systematically collect data (oncological and obstetrical outcomes) on consecutive patients treated according to institutionally defined protocols

E.C.CO. Endometrial Cancer - COnservative treatment A multicentre registry study Protocol (1) Purpose The goal of this research project is to learn more about the safety of conservatively treating EC and about subsequent fertility outcome Study Type Observational (patient registry) Study Design Observational Model (cohort) Time Perspective Prospective Endpoint Classification Treatment and outcome registry study Interventions Data collected in the registry includes patient characteristics/demographics, disease characteristics, treatment details (hormonal therapy ± surgery), disease and survival outcomes, post-intervention reproductive and obstetric outcomes Duration of the Study A first phase of three years is planned, eventually followed by further three years

Protocol (2) Outcome Measures Primary Outcome Measures E.C.CO. Endometrial Cancer - COnservative treatment A multicentre registry study Protocol (2) Outcome Measures Primary Outcome Measures proportion of complete regression duration of response frequency and pattern of relapse frequency of metachronous ovarian cancer tumor-related deaths Secondary Outcome Measures treatment related morbidity frequency of spontaneous pregnancies frequency of pregnancies after ART pattern of residual disease on definitive surgical specimens Ancillary patient serum and tumor samples collection (to be stored in situ -20°C) for future research

Protocol (3) Eligibility Inclusion Criteria age up to 40 years E.C.CO. Endometrial Cancer - COnservative treatment A multicentre registry study Protocol (3) Eligibility Inclusion Criteria age up to 40 years histologically proven EC strong desire to preserve fertility and complete the follow-up program oncology and fertility counseling and informed consent Exclusion Criteria history of previous/concomitant cancer (except for adequately treated skin basal cell or in situ cervical cancer) patient belonging to a family with hereditary non-polyposis colorectal cancer (Lynch II syndrome) synchronous ovarian cancer at magnetic resonance imaging (MRI) or laparoscopy contraindications for progestin treatment or levonorgestrel-releasing intrauterine system (LNG-IUS) insertion Treatment There is not one defined protocol (registry study), but treatment, however, is to be administered according to a IRB-approved protocol (already active protocols in Gynecologic Cancer Intergroup member institutions are incorporated in the study package and recommended) Pretreatment fertility counseling and patient informed consent are considered mandatory Pathological criteria are defined for differential diagnosis of endometrial hyperplasia and low grade adenocarcinoma Definitive surgery should be planned, and pathological data available

Data to be collected (1)

Data to be collected (2)

Data to be collected (3)

Work instructions 1) link to https://usc-intnapoli.net/v2-uosc-servizi The E.C.CO. study, endorsed by GCIG, is open since July 2014 for case registration through the following steps: Work instructions 1) link to https://usc-intnapoli.net/v2-uosc-servizi 2) create your personal account (clicking on "Ask for authorization") 3) wait for your credentials (automatically sent to your email address within 24-48h) 4) enter into to the system using your credentials and click on "Early Endometrial Cancer" for patient registration and/or updating For protocol information: s.greggi@istitutotumori.na.it or ginecologia@istitutotumori.na.it For website assistance: a.savio@usc-intnapoli.net or lucia.sparavigna@usc-intnapoli.net Study Data Center Clinical Trials Unit Istituto Nazionale dei Tumori di Napoli “Fondazione G. Pascale” IRCCS, Naples, Italy

Participation Invitation Acceptance Registration AGO-AUST (Arbeitsgemeinschaft Gynaekologische Onkologie Austria) Marth, Christian christian.marth@uki.at AGO-De (Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom Germany) Pfisterer, Jacobus jacobus.pfisterer@googlemail.com ANZGOG (Australia and New Zealand Gynecological Oncology Group) Brand, Alison Alison.Brand@swahs.health.nsw.gov.au - Quinn, Michael quinnm@ramsayhealth.com.au COGi (Cooperative Ovarian Cancer Group) Berek, Jonathan jberek@stanford.edu DGOG (Dutch Gynecologic Oncology Group) Creutzberg, Carien CL c.l.creutzberg@lumc.nl EORTC(European Organization for Research and Treatment of Cancer) Casado Herráez, Antonio antoniocasado@telefonica.net GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) Poveda, Andres apoveda@fivo.org GINECO (Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens) Hardy-Bessard, Anne-Claire ac.hardy@clin-armoricaine.fr - Pujade-Lauraine, Eric epujade@arcagy.org ​ GOTIC (Gynecologic Oncology Trial and Investigation Consortium) Fujiwara, Keiichi fujiwara@saitama-med.ac.jp ICORG (Ireland Cooperative Oncology Research Group) O' Donnell, Dearbhaile dodonnell@stjames.ie JGOG (Japanese Gynecologic Oncology Group) Aoki, Daisuke aoki@z7.keio.jp KGOG (Korean Gynecologic Oncology Group) Kim, Jae Weon kjwksh@snu.ac.kr MITO (Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies) Greggi, Stefano s.greggi@istitutotumori.na.it NCIC Clinical Trials Group (Canadian Cancer Society Research Institute) Fung-Kee-Fung, Michael mfung@ottawahospital.on.ca - Stuart​, Gavin gstuart@medd.med.ubc.ca NOGGO (Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie) Sehouli, Jalid​ jalid.sehouli@charite.de NSGO (Nordic Society of Gynecologic Oncology) Mirza, Mansoor Raza mansoor.raza.mirza@rh.regionh.dk PMHC (Princess Margaret Hospital Consortium) Oza, Amit amit.oza@uhn.ca SGCTG (Scottish Gynaecological Cancer Trials Group) Siddiqui, Nadeem nadeem.siddiqui@ggc.scot.nhs.uk SGOG (Shanghai Gynecologic Oncology Group) Chen, Xiaojun cxjlh@hotmail.com Fudan University, Shanghai, China For case registration, MITO sites please contact: s.greggi@istitutotumori.na.it Invitation Acceptance Registration