NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Gestational Trophoblastic Neoplasia Version 2.2019 — May 6, 2019 NCCN.org Continue Version 2.2019, 05/06/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Gestational Trophoblastic Neoplasia Discussion *Nadeem R. Abu-Rustum, MD Ω/Chair Patricia J. Eifel, MD § Larissa Nekhlyudov, MD, MPH Memorial Sloan Kettering Cancer Center The University of Texas Dana-Farber/Brigham and Women’s MD Anderson Cancer Center Cancer Center Catheryn M. Yashar, MD §/Vice Chair UC San Diego Moores Cancer Center Christine M. Fisher, MD, MPH § Amanda Nickles Fader, MD Ω University of Colorado Cancer Center The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Sarah Bean, MD ≠ Peter Frederick, MD Ω Duke Cancer Institute Roswell Park Cancer Institute Steven W. Remmenga, MD Ω Fred & Pamela Buffett Cancer Center Kristin Bradley, MD § David K. Gaffney, MD, PhD § University of Wisconsin Huntsman Cancer Institute *R. Kevin Reynolds, MD Ω Carbone Cancer Center at the University of Utah University of Michigan Rogel Cancer Center Susana M. Campos, MD, MPH, MS † Ernest Han, MD, PhD Ω Rachel Sisodia Ω Dana-Farber/Brigham and Women’s City of Hope Comprehensive Cancer Center Cancer Center Massachusetts General Hospital Warner K. Huh, MD Ω Todd Tillmanns, MD Ω Hye Sook Chon, MD Ω University of Alabama at Birmingham Moffitt Cancer Center St. Jude Children’s Research Hospital/ Comprehensive Cancer Center The University of Tennessee Christina Chu, MD Ω *John R. Lurain, III, MD Ω Health Science Center Fox Chase Cancer Center Robert H. Lurie Comprehensive Cancer Stefanie Ueda, MD Ω David Cohn, MD Ω Center of Northwestern University UCSF Helen Diller Family The Ohio State University Comprehensive Comprehensive Cancer Center Cancer Center - James Cancer Hospital and Andrea Mariani, MD Ω Solove Research Institute Mayo Clinic Cancer Center Emily Wyse ¥ Patient Advocate Marta Ann Crispens, MD Ω *David Mutch, MD Ω Vanderbilt-Ingram Cancer Center Siteman Cancer Center at Barnes- Jewish Hospital and Washington NCCN Shari Damast, MD § University School of Medicine Yale Cancer Center/Smilow Cancer Hospital Nicole McMillian, MS Jillian Scavone, PhD Oliver Dorigo, MD, PhD Ω Christa Nagel, MD Ω Stanford Cancer Institute Case Comprehensive Cancer Center/ University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute Ω Gynecologic oncology † Medical oncology NCCN Guidelines Panel Disclosures Continue § Radiotherapy/Radiation oncology ≠ Pathology ¥ Patient advocacy * Discussion Section Writing Committee Version 2.2019, 05/06/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Gestational Trophoblastic Neoplasia Discussion Gestational Trophoblastic Neoplasia Subcommittee David Mutch, MD Ω/Lead Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine John R. Lurain, III, MD Ω Robert H. Lurie Comprehensive Cancer Center of Northwestern University R. Kevin Reynolds, MD Ω University of Michigan Rogel Cancer Center NCCN Guidelines Panel Disclosures Continue Ω Gynecologic oncology Version 2.2019, 05/06/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Gestational Trophoblastic Neoplasia Discussion NCCN Gestational Trophoblastic Neoplasia Panel Members NCCN believes that NCCN GTN Subcommittee Members Clinical Trials: the best management for any patient with cancer is in a clinical trial. Hydatidiform Mole (Noninvasive) Participation in clinical trials is Workup, Initial Treatment, Monitoring, Findings and Additional Evaluation (HM-1) especially encouraged. Persistent Post-Molar GTN, Treatment (HM-2) To find clinical trials online at NCCN Member Institutions, click here: Gestational Trophoblastic Neoplasia (GTN) nccn.org/clinical_trials/clinicians.aspx. Workup (GTN-1) Low-Risk GTN Confirmed, Treatment, Monitoring, Follow-up/Surveillance (GTN-2) NCCN Categories of Evidence and Consensus: All recommendations Response Assessment for Low-Risk GTN (GTN-3) are category 2A unless otherwise High-Risk GTN Confirmed; Treatment (GTN-4) indicated. Intermediate Trophoblastic Tumor Confirmed, Treatment, Monitoring and Surveillance (GTN-5) See NCCN Categories of Evidence and Consensus. Principles of Systemic Therapy (GTN-A) Staging (ST-1) The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2019. Version 2.2019, 05/06/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Gestational Trophoblastic Neoplasia Discussion Updates in Version 2.2019 of the NCCN Guidelines for Gestational Trophoblastic Neoplasia from Version 1.2019 include: • The Discussion has been added to correspond with the algorithm (MS-1) Version 2.2019, 05/06/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. UPDATES NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Hydatidiform Mole (Noninvasive) Discussion WORKUP INITIAL TREATMENT MONITORING FINDINGS AND ADDITIONAL EVALUATION • H&P hCG assay Normal hCG levels • Pelvic ultrasound twice in a for 3 consecutive • Chest x-ray 3-month assays • Quantitative intervals human chorionic gonadotropin (hCG) Suction dilation • H&P 1 month assay and curettage after initial Complete • CBC differential with (D&C), preferably treatment or partial platelets under ultrasound • hCG assay hydatidiform • Liver/renal/thyroid guidanceb,c every 1–2 mole function tests/ or weeks until chemistry profile Hysterectomyd normalized • Blood type and screen hCG levels Persistent Administer Rho(D) indicate post postmolar immune globulin if molar gestational GTN Rh negative trophoblastic (See HM-2) neoplasia (GTN) aIf chest x-ray positive for metastases, manage as GTN after initial uterine evacuation. bUse largest curette feasible. Sharp curettage after suction. Use uterotonic drugs after initiating evacuation of uterus. Oxytocin receptors may be absent. cProphylactic chemotherapy with methotrexate or dactinomycin may be considered at the time of evacuation of a hydatidiform mole in patients at high risk for postmolar gestational trophoblastic neoplasia (age >40 years, hCG >100,000 mIU/mL, excessive uterine enlargement, and theca lutein cysts >6 cm) when hCG follow-up is unavailable or unreliable (Wang Q, Fu J, Hu L, et al. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database Sust Rev 2017 Sep 11;9:CD007289). dHysterectomy may be considered as initial treatment for hydatidiform mole in patients who are older or do not wish to preserve fertility. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. Version 2.2019, 05/06/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. HM-1 NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Hydatidiform Mole (Noninvasive) Discussion FINDINGS STAGING TREATMENT MONITORING hCG levels normalize hCG assay every 2 weeks until 3 Consider repeat consecutive No extrauterine D&C normal disease or assays, One or more of the Hysterectomy following indicating followed by post-molar GTN: monthly x 6 • hCG levels plateau months for 4 consecutive • H&P Persistent values over Chemotherapy • Doppler pelvic elevation 3 weeks as in GTN-1 ultrasounde (plateau or rise) • hCG levels rise • Chest x-rayf ≥10% for 3 values over 2 weeks • hCG persistence 6 months after molar evacuation Extrauterine disease Chemotherapy as in GTN-1 Histopathologic diagnosis of choriocarcinoma See GTN-1 and/or Presence of metastatic disease eDoppler pelvic ultrasound to confirm absence of pregnancy, measure uterine size, and