TY - JOUR
T1 - Survival by colon cancer stage and screening interval in Lynch syndrome
T2 - a prospective Lynch syndrome database report
AU - Dominguez-Valentin, Mev
AU - Seppälä, Toni T
AU - Sampson, Julian R
AU - Macrae, Finlay
AU - Winship, Ingrid
AU - Evans, D Gareth
AU - Scott, Rodney J
AU - Burn, John
AU - Möslein, Gabriela
AU - Bernstein, Inge
AU - Pylvänäinen, Kirsi
AU - Renkonen-Sinisalo, Laura
AU - Lepistö, Anna
AU - Lindblom, Annika
AU - Plazzer, John-Paul
AU - Tjandra, Douglas
AU - Thomas, Huw
AU - Green, Kate
AU - Lalloo, Fiona
AU - Crosbie, Emma J
AU - Hill, James
AU - Capella, Gabriel
AU - Pineda, Marta
AU - Navarro, Matilde
AU - Vidal, Joan Brunet
AU - Rønlund, Karina
AU - Nielsen, Randi Thyregaard
AU - Yilmaz, Mette
AU - Elvang, Louise Laurberg
AU - Katz, Lior
AU - Nielsen, Maartje
AU - Ten Broeke, Sanne W
AU - Nakken, Sigve
AU - Hovig, Eivind
AU - Sunde, Lone
AU - Kloor, Matthias
AU - Knebel Doeberitz, Magnus V
AU - Ahadova, Aysel
AU - Lindor, Noralane
AU - Steinke-Lange, Verena
AU - Holinski-Feder, Elke
AU - Mecklin, Jukka-Pekka
AU - Møller, Pål
PY - 2019/10/14
Y1 - 2019/10/14
N2 - Background: We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.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_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis.Results: Ninety-nine path_MMR carriers 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, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. 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_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.
AB - Background: We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.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_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis.Results: Ninety-nine path_MMR carriers 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, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. 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_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.
KW - Cancer stage
KW - Colon cancer
KW - Colonoscopy
KW - Lynch syndrome
KW - Surveillance
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85075119347&partnerID=8YFLogxK
U2 - 10.1186/s13053-019-0127-3
DO - 10.1186/s13053-019-0127-3
M3 - Journal article
C2 - 31636762
SN - 1731-2302
VL - 17
SP - 1
EP - 6
JO - Hereditary Cancer in Clinical Practice
JF - Hereditary Cancer in Clinical Practice
IS - 1
M1 - 28
ER -