British Gynaecological Cancer Society (BGCS) Uterine ...

1 Version 5 Nov 2021 [Type here] 1 British Gynaecological Cancer Society (BGCS) Uterine Cancer Guidelines: Recommendations for Practice Authors: Jo Morrison1, Janos Balega2, Lynn Buckley3, Andrew Clamp4, Emma Crosbie5, Yvette Drew6, Lisa Durrant7, Jenny Forrest8, Christina Fotopoulou9, Ketan Gajjar10, Raji Ganesan11, Janesh Gupta12, John Hughes13, Tracie Miles14, Esther Moss15, Meenu Priyadarshini Nanthakumar16, Claire Newton17, Neil Ryan17, Axel Walther18, Alex Taylor19 BGCS reviewers: Shahram Abdi, Adrian Andreou, Rebecca Bowen, John Butler, Mona El-Bahrawy, Angela George, Sadaf Ghaem-Maghami, Louise Hanna, Hilary Maxwell, Andrew Philips, Bruce Ramsay, Nithya Ratnavelu, Manpreet Singh, Sudha Sundar, Nicholas Wood.

2 International reviewers: Stefano Greggi and Nadeem Abu-Rustum Charity reviewers: Peaches Womb Cancer Trust; GO Girls; Eve Appeal 1. Jo Morrison, Department of Gynaecological Oncology, GRACE Centre, Musgrove Park hospital , Somerset NHS Foundation Trust, Taunton, TA1 5DA, UK 2. Janos Balega, Dept of Gynaecology Oncology, Pan Birmingham Gynaecological Cancer centre, City hospital School of Cancer Sciences, university of Birmingham, Birmingham, UK 3. Lynn Buckley, CNS Office, Main Admin Building, Castle Hill hospital , Hull university Teaching Hospitals NHS Trust, Castle Road, Cottingham HU16 5JQ, UK 4.

3 Andrew Clamp, The Christie NHS Foundation Trust and university of Manchester, UK 5. Emma Crosbie, Institute of Cancer Sciences, Division of Molecular and Clinical Cancer Sciences, Faculty of Biology, Medicine and Health, university of Manchester, Manchester, UK 6. Yvette Drew, Affiliation at time of contribution: Northern Centre for Cancer Care, Newcastle Hospitals NHS Foundation Trust, Newcastle, NE7 7DN, UK. Current affiliation: BC Cancer Centre Vancouver, BC, V5Z 4E6, Canada Version 5 Nov 2021 [Type here] 2 7. Lisa Durrant, Beacon Centre, Musgrove Park hospital , Somerset NHS Foundation Trust, Taunton, TA1 5DA, UK 8.

4 Jenny Forrest, Royal Devon and Exeter NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW, UK 9. Christina Fotopoulou, Dept of Surgery and Cancer , Gynaecologic Oncology, Imperial College London, UK 10. Ketan Gajjar, Nottingham university Hospitals NHS Trust, City hospital campus, Hucknall Road, Nottingham, NG5 1PB, UK 11. Raji Ganesan, Department of Cellular Pathology, Birmingham Women's hospital , Birmingham, B15 2TG, UK 12. Janesh Gupta, Centre for Women's and Newborn Health, Institute of Metabolism and Systems Research (IMSR), university of Birmingham, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B15 2TG, UK.

5 13. John Hughes, Department of Radiology, Musgrove Park hospital , Somerset NHS Foundation Trust, Taunton, TA1 5DA, UK 14. Tracie Miles, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK 15. Esther Moss, Leicester Cancer Research Centre, Room , 4th Floor, Robert Kilpatrick Building university of Leicester, Leicester LE2 7LX, UK 16. Meenu Priyadarshini Nanthakumar, Birmingham Women's and Children's hospital , Birmingham, B15 2TG, UK 17 Claire Newton, Gynaecology Oncology Department, St Michael s hospital , university Hospitals bristol NHS Foundation Trust, bristol , BS1 3NU 17 and 18.

6 Neil Ryan, Gynaecology Oncology Department, St Michael s hospital , university Hospitals bristol NHS Foundation Trust, bristol , BS1 3NU, UK and The Academic Women s Health Unit, Translational Health Sciences, bristol Medical School, university of bristol , bristol , UK 18. Axel Walther, bristol Cancer Institute, university Hospitals bristol and Weston NHS Trust, bristol , UK 19. Alex Taylor, Royal Marsden NHS Foundation Trust, London, UK Version 5 Nov 2021 [Type here] 3 Table of Contents 1 Introduction _____ 7 Methodology _____7 Hierarchy of evidence _____ 7 Guideline development process _____ 7 Management of conflict of interest _____8 2 Background _____ 8 Epidemiology _____8 Molecular Classification _____8 Clinical implications of the molecular classification of endometrial Cancer _____ 11 Screening and prevention _____ 13 Screening _____ 13 Screening in the general population _____ 13 Screening in high-risk groups _____ 13 Prevention in the general population_____ 15

7 Prevention in high-risk groups _____ 16 3 Presentation and diagnosis_____ 17 Presenting Symptoms _____ 17 Diagnostic methods_____ 18 History and examination _____ 18 Indications for referral _____ 19 Investigations _____ 19 Pathways for management of endometrial Cancer _____ 24 Where women are treated _____ 26 After treatment _____ 26 Version 5 Nov 2021 [Type here] 4 Failsafe _____ 27 4 Imaging and pre-operative work-up _____ 27 Pre-operative investigations_____ 27 Imaging _____ 28 5 Pathology of endometrial Cancer _____ 30 6 Primary treatment of endometrial carcinoma with surgery _____ 32 Route of surgery _____ 34 Management of lymph nodes _____ 35 Sentinel lymph node sampling _____ 37 Pelvic and para-aortic node dissection _____ 38 Surgical management of overt stage II disease _____ 39 7 Primary treatment - non-surgical management _____ 39 Patients unfit for surgical management

8 _____ 39 Fertility-preserving management _____ 40 Surgery for more advanced disease at presentation _____ 42 8 Primary treatment adjuvant treatment _____ 44 Low-risk endometrial Cancer _____ 45 Intermediate-risk endometrial Cancer _____ 45 High-intermediate-risk endometrial Cancer _____ 48 High-risk endometrial Cancer _____ 50 Adjuvant chemotherapy _____ 51 Adjuvant hormonal therapy _____ 57 Adjuvant radiotherapy _____ 57 External beam radiotherapy (EBRT) technique_____ 57 Version 5 Nov 2021 [Type here] 5 Vaginal brachytherapy _____ 58 9 Primary treatment - chemotherapy _____ 58 Neoadjuvant chemotherapy _____ 59 Palliative systemic therapy _____ 60 10 Primary Treatment - radiotherapy _____ 61 11 Management of recurrent disease _____ 62 Work up prior to treatment for recurrent disease _____ 63 Treatment of recurrent disease _____ 63 Locoregional recurrence _____ 64 Oligometastatic recurrence _____ 66 Multi-site recurrence _____ 67 12 Management of Uterine sarcoma _____ 71 Leiomyosarcoma (LMS)

9 _____ 72 Early stage leiomyosarcoma _____ 73 Advanced stage or recurrent leiomyosarcoma _____ 77 Endocrine therapies _____ 80 Endometrial stromal sarcoma (ESS) _____ 80 Early-stage endometrial stromal sarcoma _____ 81 Recurrent or metastatic endometrial stromal sarcoma _____ 82 Uterine adenosarcoma _____ 83 Management of early-stage Uterine adenosarcomas _____ 84 13 Follow up after treatment _____ 85 Follow-up for endometrial Cancer _____ 85 Technique _____ 87 Version 5 Nov 2021 [Type here] 6 Stratified follow up _____ 87 Eliciting symptoms at follow-up _____ 89 Follow-up for Uterine sarcomas _____ 90 14 Supportive care _____ 90 Clinical nurse specialist (CNS)

10 Support and holistic needs _____ 92 Psychosocial _____ 92 Sexuality/sexual morbidity _____ 93 Hormone replacement therapy (HRT) following treatment for endometrial Cancer _____ 93 Lymphoedema _____ 94 Management of late effects of treatment _____ 94 Gastrointestinal (GI) late effects _____ 95 Urinary tract late effects_____ 96 Management of pelvic insufficiency fractures (PIF) _____ 97 Management of neuropathy and lumbosacral plexopathy _____ 98 15 Research priorities _____ 99 16 Glossary _____ 100 17 Declared Conflicts of Interest _____ 103 18 Appendices _____ 105 19 References _____ 121 Version 5 Nov 2021 [Type here] 7 1 Introduction Methodology The remit of this guideline is to collate and propose evidence-based guidelines for the diagnosis and management of Uterine Cancer .