N31: Identification Of Clinical, Genetic And Endoscopic Predictors Of Incident Colorectal Cancer In Lynch Syndrome

A. Sanchez Garcia1, M. Navarro2, L. Moreno1, T. Ocaña1, M. Pineda2, F. Rodriguez-Moranta3, L. Rodríguez-Alonso3, A. Soriano3, T. Ramon y Cajal4, G. Llort5, C. Yagüe5, M. Dolores Picó6, R. Jover6, A. Lopez-Fernandez7, E. Martinez Castro8, C. Alvarez9, X. Bessa9, L. Rivas10, J. Cubiellas10, D. Rodriguez-Alcalde11, A. Dacal12, M. Herraiz13, C. Garau14, L. Bujanda15, L. Cid16, C. Poves17, M. Garzon18, A. Pizarro18, I. Salces19, M. Ponce20, M. Carrillo-Palau21, E. Aguirre22, E. Seperas23, A. Suarex24, V. Piñol25, R. Lleuger25, E. Martinez-Bauer26, C. Romero27, A. Gisbert4, G. Jung1, S. Carballal1, L. Rivero1, M. Pellisé1, J. Balmaña7, J. Brunet2, 25, A. Castells1, G. Capellà2, L. Moreira1, M. Serra28, F. Balaguer1

1 – Hospital Clinic Barcelona, Barcelona, Spain. 2 – Institut Català d’Oncología, Barcelona, Spain. 3 – Hospital Universtari de Bellvitge, Barcelona, Spain. 4 – Hospital de la Santa Creu i San Pau, Barcelona, Spain. 5 – Corporació Sanitària Parc Tauli i Consorci Sanitari de Terrasa, Sabadell i Terrasa, Spain. 6 – Hospital General Universitario de Alicante, Alicante, Spain. 7 – Hospital Universitari Vall d’Hebron, Barcelona, Spain. 8 – Hospital Universitario Marques de Valdecilla, Santander, Spain. 9 – Hospital del Mar, Barcelona, Spain. 10 – Complexo Hospitalario Universitario de Ourense, Ourense, Spain. 11 – Hospital Universitario de Móstoles, Mostoles, Spain. 12 -Hospital Universitario Lucus Augusti, Lugo, Spain. 13 – Clinica Universitaria de Navarra, Pamplona, Spain. 14 – Hospital de Son Llatzer, Palma de Mallorca, Spain. 15 – Hospital Universitario de Donostia, Donostia, Spain. 16 – Hosptial Álvaro Cunqueiro de Vigo, Vigo, Spain. 17 – Hospital Clínico de San Carlos, Madrid, Spain. 18 – Hospital Universitario Virgen del Rocío, Sevilla, Spain. 19 – Hospital Universitario 12 de Octubre, Madrid, Spain. 20 – Hospital Universitari i Politècnic de la Fe de València, Tenerife, Spain. 21 – Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain. 22 – Hospital Quiron de Zaragoza, Zaragoza, Spain. 23 – Hospital General de Catalunya, Barcelona, Spain. 24 – Hospital Universitario Central de Asturias, Oviedo, Spain. 25 – Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain. 26 – Hospital Parc Taulí, Sabadell, Spain. 27 – Consorci Sanitari de Terrasa, Terrasa, Spain. 28 – Universitat de Barcelona Centre de Recerca en Economia i Salut (Cres-UPF), Barcelona, Spain.

 

Aim: Lynch syndrome (LS) families have a high risk of colorectal cancer (CRC) during their lifetime. Colonoscopy every <3 years decreases incidence and mortality of CRC. However, recent studies show that up to 40% of carriers develop CRC during colonoscopy follow-up at the age of 70. It is crucial to identify the factors that predict CRC development in this setting to further improve prevention in LS. Endoscopy quality indicators in the setting of Lynch screening have been poorly studied.

This study is designed to assess the clinic-pathological, genetic and endoscopy factors that predict the development of CRC during colonoscopy surveillance in LS mutation carriers.

Method: Multicenter nation-wide study in Spain, with retrospective collection of prospectively observed data in the setting of organized high-risk clinics. A centralized online database was used, including demographic, genetic, family and personal cancer history, and surveillance protocol and treatments, from September 2015 to October 2017. First prospectively complete colonoscopy planned as LS screening was considered as date of inclusion. Cumulative incidence of the first CRC diagnosed under screening was calculated by mutated gene and gender. For this analysis, CRCs diagnosed prior or within the first colonoscopy (prevalent cancers) were excluded. Additionally, endoscopic predictor factors of CRC have been analyzed.

Results: We included 1,108 LS cases, 631 female (56.9%), with a median age of 53 year (SD 15.4), and a median follow-up of 50.85 months (SD 47.6). Distribution per gene was: 449 (40.5%) MLH1, 371 (33.6%) MSH2, 197 (17.9%) MSH6, 68 (6.1%) PMS2 and 23 (2.1%) EPCAM. The prevalence of CRC was 41.42% (459). Five-hundred-thirty-eight healthy carriers with proven endoscopic surveillance were selected from all the healthy carriers (666) from whom we could obtain endoscopic reports. Seventeen (17/538) incident CRC were diagnosed during endoscopic screening in healthy carriers: 7/191 MLH1, 9/192 MSH2, 1/113 MSH6, 0/37 PMS2 and 0/5 EPCAM. Inadequate endoscopic follow-up was present in 7/17 incident CRC including longer than 3 years interval (n=4) or inadequate bowel cleansing (n=3) (Table.1). Cumulative CRC incidence at 70 years under endoscopic follow-up was calculated per gen (Figure.1): 13.8% (95%CI:5.9-30.3%) for MLH1; 18.5% (95%CI: 8.8-36.4%) for MSH2 and 1% (95%CI: 0.15-7.1%) for MSH6; and per gender (Figure.2): 16.7% (95%CI: 8-32.1%) for males and 8.7% (95% CI: 3.9-19%) for females.

Conclusion: In this large Spanish multicenter study, a preliminary analysis reveals that cumulative incidence of the first CRC under screening colonoscopy is lower than previously published. Our results suggest that colonoscopy is highly effective for CRC prevention in LS, and that high quality endoscopic standards are key for its effectiveness.

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