The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome

Emma J Crosbie,Pål Møller,Gabriela Möslein,Noah D Kauff,Ian Martin Frayling ,Sarah Kitson ,Diana Eccles,Neil Ryan ,Adam N Rosenthal ,Peter Sasieni,Tjalling Bosse,Joanna M Cornes,Ranjit Manchanda,Raymond Mcmahon ,John Burn,Naveena Singh,Robin Crawford,Kevin Monahan ,Pauline Skarrott,Heather Hampel,Marc Tischkowitz,Sadaf Ghaem‐Maghami ,Robert Steele,Usha Menon,Mark J Arends,Mourad W Seif,Henry C Kitchener ,Tristan Snowsill ,D Gareth Evans

doi:10.1038/s41436-019-0489-y

Abstract

PurposeThere are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients. MethodsStakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice. ResultsGuidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer. ConclusionThis document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care.

Highlights

Lynch syndrome is an autosomal dominantly inherited cancer syndrome including colorectal (CRC), endometrial (EC), and ovarian cancer (OC).[1]. It is caused by pathogenic variants of the DNA mismatch repair (MMR) system genes MLH1, MSH2, MSH6, and PMS2, which prevent the correction of acquired errors during DNA synthesis
Day 1 consisted of 11 lectures covering the prevalence of Lynch syndrome and its associated cancer risks, the patient’s perspective, the process of developing clinical guidance, lessons learned from the colorectal community, current diagnostic technologies, and methods of gynecological surveillance
Screening for Lynch syndrome in women affected by cancers of the lower genital tract is not recommended, with the exception of (HPV-independent) endocervical adenocarcinomas, given the difficulty of distinguishing them from lower uterine segment endometrial cancers.[26]

Summary

Results

Guidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer

Conclusion

INTRODUCTION

DISCUSSION