Survival outcomes associated with Lynch syndrome colorectal cancer and metachronous rate after subtotal/total versus segmental colectomy: Meta-analysis

Published:August 28, 2022DOI:



      Lynch syndrome is associated with the most common form of heritable bowel cancer. There remains limited level 1 evidence on survival outcomes and rate of metachronous tumor associated with Lynch syndrome colorectal cancer.


      A systematic literature search of original studies was performed on Ovid searching MEDLINE, Embase, Cochrane Database of Systematic Reviews, American College of Physicians ACP Journal Club, Database of Abstracts of Reviews of Effects DARE, and Clinical Trials databases from inception of database to February 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was followed. The data were pooled using a random-effects model. All of the P values were 2-tailed, and statistical analysis was performed using RevMan v. 5.3 Cochrane Collaboration.


      From 1,942 studies, 15 studies met the inclusion criteria and were included for qualitative and quantitative synthesis. The five-year overall survival was 89.5% (82.0–94.1%), P < .01; I2 = 89%. The ten-year overall survival was 80.5% (68.7–88.6%), P < .01; I2 = 81%. The fifteen-year overall survival was 70% (33.7%-91.5%), P < .01; I2 = 93%. Univariate meta-regression analysis showed no statistically significant difference in 5-year overall survival by sex, age, MLH1, MSH2, MSH6, nor tumor location (right versus left colon). The metachronous tumor rate was 12% to 33% with a follow-up period of up to 15 years, significantly lower in patients who underwent subtotal/total colectomy (0–6%).


      The overall survival of patients with colorectal cancer with Lynch syndrome was approximately 90% at 5 years, 80% at 10 years, and 70% at 15 years. The metachronous tumor rate was approximately 10% to 30% at up to 15 years, significantly improved by subtotal/total colectomy.
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        • Sung H.
        • Ferlay J.
        • Siegel R.L.
        • et al.
        Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2021; 71: 209-249
        • Edelstein D.L.
        • Axilbund J.
        • Baxter M.
        • et al.
        Rapid development of colorectal neoplasia in patients with Lynch syndrome.
        Clin Gastroenterol Hepatol. 2011; 9: 340-343
        • Toh J.W.T.
        • Phan K.
        • Reza F.
        • Chapuis P.
        • Spring K.J.
        Rate of dissemination and prognosis in early and advanced stage colorectal cancer based on microsatellite instability status: systematic review and meta-analysis.
        Int J Colorect Dis. 2021; 36: 1573-1596
        • Kazama Y.
        • Watanabe T.
        • Kanazawa T.
        • Tanaka J.
        • Tanaka T.
        • Nagawa H.
        Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features.
        J Clin Pathol. 2007; 60: 701-704
        • Xiao H.
        • Yoon Y.S.
        • Hong S.M.
        • et al.
        Poorly differentiated colorectal cancers: correlation of microsatellite instability with clinicopathologic features and survival.
        Am J Clin Pathol. 2013; 140: 341-347
        • Thibodeau S.N.
        • Bren G.
        • Schaid D.
        Microsatellite instability in cancer of the proximal colon.
        Science. 1993; 260: 816-819
        • Yoon Y.S.
        • Kim J.
        • Hong S.M.
        • et al.
        Clinical implications of mucinous components correlated with microsatellite instability in patients with colorectal cancer.
        Colorect Dis. 2015; 17: O161-O167
        • Karahan B.
        • Argon A.
        • Yildirim M.
        • Vardar E.
        Relationship between MLH-1, MSH-2, PMS-2, MSH-6 expression and clinicopathological features in colorectal cancer.
        Int J Clin Exp Pathol. 2015; 8: 4044-4053
        • Soreide K.
        • Slewa A.
        • Stokkeland P.J.
        • et al.
        Microsatellite instability and DNA ploidy in colorectal cancer: potential implications for patients undergoing systematic surveillance after resection.
        Cancer. 2009; 115: 271-282
        • Yun H.R.
        • Yi L.J.
        • Cho Y.K.
        • et al.
        Double Primary Malignancy in Colorectal Cancer Patients: MSI Is the Useful Marker for Predicting Double Primary Tumors.
        4th ed. Springer Nature, London, UK2009: 369-375
        • Hu H.
        • Chang D.T.
        • Nikiforova M.N.
        • Kuan S.F.
        • Pai R.K.
        Clinicopathologic Features of Synchronous Colorectal Carcinoma: A Distinct Subset Arising From Multiple Sessile Serrated Adenomas and Associated With High Levels of Microsatellite Instability and Favorable Prognosis.
        11th ed. Lippincott Williams and Wilkins, Philadelphia, PA2013: 1660-1670
        • Popat S.
        • Hubner R.
        • Houlston R.S.
        Systematic review of microsatellite instability and colorectal cancer prognosis.
        J Clin Oncol. 2005; 23: 609-618
        • Guastadisegni C.
        • Colafranceschi M.
        • Ottini L.
        • Dogliotti E.
        Microsatellite instability as a marker of prognosis and response to therapy: a meta-analysis of colorectal cancer survival data.
        Eur J Cancer. 2010; 46: 2788-2798
        • Toh J.W.
        • de Souza P.
        • Lim S.H.
        • et al.
        The potential value of immunotherapy in colorectal cancers: review of the evidence for programmed death-1 inhibitor therapy.
        Clin Colorect Cancer. 2016; 15: 285-291
        • Toh J.
        • Chapuis P.H.
        • Bokey L.
        • Chan C.
        • Spring K.J.
        • Dent O.F.
        Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer.
        Br J Surg. 2017; 104: 1250-1259
        • Toh J.W.T.
        • Lim S.H.
        • MacKenzie S.
        • et al.
        Association between microsatellite instability status and peri-operative release of circulating tumour cells in colorectal cancer.
        Cells. 2020; 9: 425
        • Dominguez-Valentin M.
        • Sampson J.R.
        • Seppälä T.T.
        • et al.
        Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.
        Genet Med. 2020; 22: 15-25
        • Akinkuotu A.C.
        • Maduekwe U.N.
        • Hayes-Jordan A.
        Surgical outcomes and survival rates of colon cancer in children and young adults.
        Am J Surg. 2021; 221: 718-724
        • Renkonen-Sinisalo L.
        • Seppala T.T.
        • Jarvinen H.J.
        • Mecklin J.P.
        Subtotal colectomy for colon cancer reduces the need for subsequent surgery in Lynch syndrome.
        Dis Colon Rect. 2017; 6079279
        • Parry S.
        • Win A.K.
        • Parry B.
        • et al.
        Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery.
        Gut. 2011; 60: 950-957
        • Kim T.J.
        • Kim E.R.
        • Hong S.N.
        • et al.
        Survival outcome and risk of metachronous colorectal cancer after surgery in Lynch syndrome.
        Ann Surg Oncol. 2017; 24: 1085-1092
        • Win A.K.
        • Parry S.
        • Parry B.
        • et al.
        Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers.
        Ann Surg Oncol. 2013; 20: 1829-1836
        • Xu Y.
        • Li C.
        • Zheng C.Z.
        • et al.
        Comparison of long-term outcomes between Lynch sydrome and sporadic colorectal cancer: a propensity score matching analysis.
        BMC Cancer. 2021; 21: 45
        • Moller P.
        • Seppala T.
        • Bernstein I.
        • et al.
        Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database.
        Gut. 2017; 66: 464-472
        • Dominguez-Valentin M.
        • Seppälä T.T.
        • Sampson J.R.
        • et al.
        Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report.
        Hered Cancer Clin Pract. 2019; 17: 28
        • Page M.J.
        • McKenzie J.E.
        • Bossuyt P.M.
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Xu Y.
        • Li C.
        • Wang Z.
        • Liu F.
        • Xu Y.
        Comparison of suspected Lynch syndrome patients carrying BRCA and BRCA-like variants with Lynch syndrome probands: phenotypic characteristics and pedigree analyses.
        Mol Genet Genomic Med. 2020; 8: e1359
        • Hiatt M.J.
        • Casey M.J.
        • Lynch H.T.
        • Snyder C.L.
        • Stacey M.
        • Walters R.W.
        Efficacy of proximal colectomy for surgical management of right-sided first colorectal cancer in Lynch syndrome mutation carriers.
        Am J Surg. 2018; 216: 99-105
        • Nagasaki T.
        • Arai M.
        • Chino A.
        • Akiyoshi T.
        • Fukunaga Y.
        • Ueno M.
        Feasibility of segmental colectomy followed by endoscopic surveillance as a treatment strategy for colorectal cancer patients with Lynch syndrome.
        Dig Surg. 2018; 35: 448-456
        • Brixen L.M.
        • Bernstein I.T.
        • Bülow S.
        • Ehrnrooth E.
        Survival of patients with stage III colon cancer is improved in hereditary non-polyposis colorectal cancer compared with sporadic cases: a Danish registry based study.
        Colorect Dis. 2013; 15: 816-823
        • Stupart D.A.
        • Goldberg P.A.
        • Baigrie R.J.
        • Algar U.
        • Ramesar R.
        Surgery for colonic cancer in HNPCC: total vs segmental colectomy.
        Colorect Dis. 2011; 13: 1395-1399
        • Russo A.
        • Sala P.
        • Alberici P.
        • et al.
        Prognostic relevance of MLH1 and MSH2 mutations in hereditary non-polyposis colorectal cancer patients.
        Tumori. 2009; 95: 731-738
        • Zlobec I.
        • Molinari F.
        • Kovac M.
        • et al.
        Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients.
        Br J Cancer. 2010; 102: 151-161
        • Elsakov P.
        • Kurtinaitis J.
        Survival from colorectal carcinoma in HNPCC families as compared to the general population in Lithuania: initial results.
        Fam Cancer. 2006; 5: 369-371
        • Barnetson R.A.
        • Tenesa A.
        • Farrington S.M.
        • et al.
        Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer.
        N Engl J Med. 2006; 354: 2751-2763
        • National Cancer Institute (NCI)
        Surveillance EaERP. 2010–2016.
        Date accessed: December 12, 2021
        • de Jong A.E.
        • Hendriks Y.M.
        • Kleibeuker J.H.
        • et al.
        Decrease in mortality in Lynch syndrome families because of surveillance.
        Gastroenterology. 2006; 130: 665-671
        • Giardiello F.M.
        • Allen J.I.
        • Axilbund J.E.
        • et al.
        Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer.
        Dis Colon Rectum. 2014; 57: 1025-1048
        • Gryfe R.
        • Kim H.
        • Hsieh E.T.
        • et al.
        Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer.
        N Engl J Med. 2000; 342: 69-77
        • Bui Q.M.
        • Lin D.
        • Ho W.
        Approach to Lynch syndrome for the gastroenterologist.
        Dig Dis Sci. 2017; 62: 299-304
        • Sheikh R.A.
        • Min B.H.
        • Teplitz R.
        • Tesluk H.
        • Ruebner B.H.
        • Lawson M.J.
        Why hereditary nonpolyposis colorectal carcinoma patients appear to have better survival than patients with sporadic colorectal carcinoma.
        Cancer. 1999; 85: 253-254
        • You Y.N.
        • Chua H.K.
        • Nelson H.
        • Hassan I.
        • Barnes S.A.
        • Harrington J.
        Segmental vs. extended colectomy: measurable differences in morbidity, function, and quality of life.
        Dis Colon Rectum. 2008; 51: 1036-1043
        • Haanstra J.F.
        • de Vos Tot Nederveen Cappel W.H.
        • Gopie J.P.
        • et al.
        Quality of life after surgery for colon cancer in patients with Lynch syndrome: partial versus subtotal colectomy.
        Dis Colon Rectum. 2012; 55: 653-659
        • Haanstra J.F.
        • tot Nederveen WHdV.
        • Gopie J.P.
        • et al.
        Quality of life after surgery for colon cancer in patients with Lynch syndrome: partial versus subtotal colectomy.
        Dis Colon Rectum. 2012; 55: 653-659
        • Urso E.D.
        • Celotto F.
        • Giandomenico F.
        • et al.
        Analysis of morbidity and mortality, quality of life and bowel function after total colectomy with ileorectal anastomosis versus right and left hemicolectomy: a study to optimise the treatment of lynch syndrome and attenuated polyposis coli.
        Eur J Surg Oncol. 2020; 46: 1613-1619
        • Herzig D.O.
        • Buie W.D.
        • Weiser M.R.
        • et al.
        Clinical practice guidelines for the surgical treatment of patients with Lynch syndrome.
        Dis Colon Rectum. 2017; 60: 137-143
        • Sun J.
        • Dong M.
        • Xiao X.
        Efficacy, functional outcome and post-operative complications of total abdominal colectomy with ileorectal anastomosis vs. segmental colectomy in hereditary non-polyposis colorectal cancer.
        Exp Ther Med. 2018; 16: 1603-1612
        • Burn J.
        • Sheth H.
        • Elliott F.
        • et al.
        Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial.
        Lancet. 2020; 395: 1855-1863