Survival by colon cancer stage and screening interval in Lynch Syndrome: a Prospective Lynch Syndrome Database report

Mev Dominguez-Valentin1, Toni T. Seppälä2,3, Julian R. Sampson4, Finlay Macrae5,6, Ingrid Winship5,6, D. Gareth Evans7, Rodney J. Scott8, John Burn9, Gabriela Möslein10, Inge Bernstein11, Kirsi Pylvänäinen12, Laura Renkonen-Sinisalo13,14, Anna Lepistö13,14, Annika Lindblom15, John-Paul Plazzer5, Douglas Tjandra6, Huw Thomas16, Kate Green7, Fiona Lalloo7, Emma J. Crosbie17, James Hill7, Gabriel Capella18, Marta Pineda18, Matilde Navarro18, Joan Brunet Vidal18, Karina Rønlund19, Randi Thyregaard Nielsen20, Mette Yilmaz21, Louise Laurberg Elvang22, Lior Katz23, Maartje Nielsen24, Sanne W. ten Broeke24, Sigve Nakken1, Eivind Hovig1, Lone Sunde25, Matthias Kloor26, Magnus v Knebel Doeberitz26, Aysel Ahadova26, Noralane Lindor27, Verena Steinke-Lange28,29, Elke Holinski-Feder28,29, Jukka-Pekka Mecklin30,31, Pål Møller1

1Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway. 2Helsinki University Central Hospital, Department of Gastrointestinal Surgery, Helsinki, Finland, Helsinki, Finland. 3Clinicum, University of Helsinki, Helsinki, Finland, Helsinki, Finland. 4Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, Cardiff, United Kingdom. 5The Royal Melbourne Hospital, Melbourne, Australia. 6University of Melbourne, Melbourne, Australia. 7University of Manchester & Manchester University Hospitals Foundation Trust, Manchester, United Kingdom. 8University of Newcastle and the Hunter Medical Research Institute, Newcastle, Australia. 9University of Newcastle, Newcastle upon Tyne, Newcastle, United Kingdom. 10University Witten-Herdecke, Wuppertal, Germany. 11Dept. of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark. 12Central Finland Central Hospital, Education and Research, Jyväskylä, Finland. 13Helsinki University Central Hospital, Department of Gastrointestinal Surgery, Helsinki, Finland. 14Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki, Finland. 15Karolinska Institutet, Stockholm, Sweden, Stockholm, Sweden. 16St Mark’s Hospital, Department of Surgery and Cancer, Imperial College London, London, United Kingdom. 17University of Manchester and St Mary’s Hospital, Manchester, Manchester, United Kingdom. 18Hereditary Cancer Program, Catalan Institute of Oncology, Insititut d’Investigació Biomèdica de Bellvitge (IDIBELL), ONCOBELL Program, L’Hospitalet de Llobregat, Barcelona, Spain, and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain. 19Dept. of Clinical Genetics, Vejle Hospital, Velje, Denmark. 20Dept. of Surgery, Regional Hospital West Jutland, West Jutland, Denmark. 21Dept. of Oncology, Aalborg University Hospital, Aalborg, Denmark. 22Dept. of Pathology, Herlev Gentofte University Hospital, Herlev, Herlev, Denmark. 23High Risk and GI Cancer prevention Clinic, Gatro-Oncology Unit, The Department of Gastroenterology, Sheba Medical Center, Sheba, Israel. 24Leids Universitair Medisch Centrum, Leiden, Leiden, Netherlands. 25Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. 26Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, and Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 27Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizone, USA. 28Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany. 29MGZ- Medical Genetics Center, Munich, Germany. 30Dept. of Surgery, Central Finland Central Hospital, Jyväskylä, Finland. 31Faculty of Sport and Health Sciences, Jyväskylä, Finland


Aims.To determine if survival after colon cancer differs according to the intervals of colonoscopies undertaken prior to cancer diagnosis in path_MMR carriers.

Methods. The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMRvariants scored by the InSiGHT variant database as class 4 or 5 were included in the analysis.

Results. Ninety-ninepath_MMRcarriers had no cancer prior to or at first colonoscopy but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis andincluded 77 path_MLH1, 17 path_MSH2,and 2 path_MSH6carriers. The number of cancers detected within <1.5, 1.5–2.5, 2.5–3.5 and at >3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93%, 94% and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been <1.5, 1.5–2.5, 2.5–3.5 or >3.5 years before diagnosis, was 89%, 90%, 90% and 92%, respectively (p=0.91).

Conclusions. In path_MMR carriers, more advanced colon cancer stage was associated with poorer survival whereas time since previous colonoscopy was not. Together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMRvariant carriers with colonoscopy intervals of less than 3 years provides significant benefit.