A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

作者：Elizabeth Bancroft, Elizabeth Page, Mark N. Brook, Sarah Thomas, Natalie Taylor, Jennifer Pope, Jana McHugh, Ann-Britt Jones, Questa Karlsson, Susan Merson, Kai Ren Ong, Jonathan Hoffman, Camilla Huber, Lovise Mæhle, Eli Marie Grindedal, Astrid Stormorken, D. Gareth Evans, Jeanette Rothwell, Fiona Lalloo, Angela F. Brady, Marion Bartlett, Katie Snape, Helen Hanson, Paul A. James, Joanne McKinley, Lyon Mascarenhas, Sapna Syngal, Chinedu Ukaegbu, Lucy Side, Tessy Thomas, Julian Barwell, Manuel R. Teixeira, Louise Izatt, Mohnish Suri, Finlay Macrae, Nicola Poplawski, Rakefet Chen‐Shtoyerman, Munaza Ahmed, Hannah Musgrave, Nicola Nicolai, Lynn Greenhalgh, Carole Brewer, Nicholas Pachter, Allan D. Spigelman, Ashraf Azzabi, Brian T. Helfand, Dorothy Halliday, Saundra S. Buys, Teresa Ramón y Cajal, Alan Donaldson, Kathleen A. Cooney, Marion Harris, John McGrath, Rosemarie Davidson, Amy Taylor, Peter Cooke, Kathryn Myhill, Matthew Hogben, Neil K. Aaronson, Audrey Ardern‐Jones, Chris H. Bangma, Elena Castro, David P. Dearnaley, Alexander Dias, Tim Dudderidge, Diana M Eccles, Kate Green, Jórunn E. Eyfjörd, Alison Falconer, Christopher S. Foster, Henrik Grönberg, Freddie C. Hamdy, Oskar T. Johannsson, Vincent Khoo, Hans Lilja, Geoffrey J. Lindeman, Jan Lubiński, Karol Axcrona, Christos Mikropoulos, Anita Mitra, Clare Moynihan, Holly Ní Raghallaigh, Gad Rennert, Rebecca Collier, Lisa K. Adams, Julian Adlard, Rosa Alfonso, Saira Ali, Angela Andrew, Luís Araújo, Nazya Azam, Darran Ball, Queenstone Barker, Alon Basevitch, Barbara Benton, Cheryl Berlin, Nicola Bermingham, Leah H. Biller, Angela Bloss, Matilda Bradford, Nicola Bradshaw, Amy Branson, Charles B. Brendler, Maria Brennan, Barbara Bulman, Lucy Burgess, Declan Cahill, Alice Callard, Nuria Calvo Verges, Marta Cardoso, Vanda Carter, Mario Catanzaro, Anthony Chamberlain, Cyril Chapman, Michael Chong, Caroline Clark, Virginia Clowes, Lyn Cogley, Trevor Cole, Cecilia Compton, Tom Conner, Sandra Cookson, Philip Cornford, Philandra Costello, Laura Coulier, Michaela Davies, Christopher Dechet, Bianca DeSouza, Gemma Devlin, Fiona Douglas, Emma Douglas, Darshna Dudakia, Alexis E. Duncan, Natalie Ellery, Sarah Everest, Sue Freemantle, Mark Frydenberg, D.B. Fuller, Camila Pires Cremasco Gabriel, Madeline Gale, Lynda Garcia, Simona Gay, Elena Genova, Angela George, Demetra Georgiou, A Gisbert, Margaret Gleeson, Wayne Glover, Vincent J. Gnanapragasam, Sally Goff, David E. Goldgar, Nuno Gonçalves, Selina Goodman, Jennifer Gorrie, Hannah Gott, Anna Grant, Catherine Gray, Julie Griffiths, Karin Gupwell, Jana Gurasashvili, Eldbjørg Hanslien, Sigurdís Haraldsdóttir, Rachel Hart, Catherine Hartigan, Lara Hawkes, Tricia Heaton, Alex Henderson, Rui Henrique, Kathrine Hilario, Kathryn Hill, Peter J. Hulick, Clare Hunt, Melanie Hutchings, Rita Ibitoye, Thomas Inglehearn, Joanna Ireland, Farah Islam, Siti Ismail, Chris Jacobs, Denzil James, Sharon Jenkins, Irene Jobson, Anne Johnstone, Oliver Jones, Sagi Josefsberg Ben‐Yehoshua, Beckie Kaemba, Karen L. Kaul, Zoe Kemp, Netty Kinsella, Margaret Klehm, Roger Kockelbergh, Kelly Kohut, Monika Kosicka‐Slawinska, Anjana Kulkarni, Pardeep Kumar, Jimmy Lam, Mandy LeButt, Dan Leibovici, Ramona M. Lim, Lauren Limb, Claire Lomas, Mark Longmuir, Consol López, Tiziana Magnani, Sofia Maia, Jessica Maiden, Alison Male, Merrie Manalo, Phoebe Martin, Donna McBride, Michael McGuire, Romayne McMahon, Claire McNally, Terri McVeigh, Ehud Melzer, Mark Mencias, Catherine Mercer, Gillian Mitchell, Josefina Móra, Catherine Morton, Cathryn Moss, Morgan Murphy, Declan G. Murphy, Shumi Mzazi, Maria Nadolski, Anna Newlin, Pedro Nogueira, Rachael O’Keefe, Karen O’Toole, Shona O’Connell, Chris Ogden, Linda A. Okoth, Jorge Oliveira, Edgar Páez, Joan Palou, Linda Park, Nafisa Patel, J Maria Medeiros Souto, A. Pearce, Ana Peixoto, Kimberley Perez, Lara Petelin, Gabriella Pichert, Charlotte Poile, Alison J. Potter, Nadia Preitner, Helen Purnell, Ellie Quinn, Paolo Radice, Brigette Rankin, K. R. Rees, Caroline Renton, Kate Richardson, Peter Risby, Jason Rogers, Maggie Ruderman, April Ruiz, Anaar Sajoo, Natale Salvatore, Victoria Sands, Francesco Sanguedolce, Abdul Sattar, Kathryn J. Saunders, Lyn Schofield, Rodney J. Scott, Anne Searle, Ravinder Sehra, Christina G. Selkirk, Kylie Shackleton, Sue Shanley, Adam Shaw, Daniel H. Shevrin, Hannah Shipman, Zahirah Sidat, Kas Siguake, Kate Simon, Courtney Smyth, Lesley Snadden, Nita Solanky, Joyce Solomons, Margherita Sorrentino, Barbara Stayner, Robert L. Stephenson, Elena M. Stoffel, Maggie Thomas, Alan Thompson, Lizzie Tidey, Marc Tischkowitz, Audrey Torokwa, Sharron Townshend, Katy Treherne, Karen Tricker, Quoc‐Dien Trinh, Vishakha Tripathi, Clare Turnbull, R. Valdagni, Nicholas van As, Vickie L. Venne, Lizzie Verdon, Marco Vitellaro, Kristen J. Vogel, Lisa Walker, Amy Watford, Cathy Watt, Ilana Weintroub, Shelly M. Weiss, Scott M. Weissman, Michelle Weston, Jennifer Wiggins, Gillian Wise, Christopher Woodhouse, Pembe Yesildag, Alice Youngs, Matthew B. Yurgelun, Fabiana Zollo, Judith Offman, Zsofia Kote‐Jarai, Rosalind A. Eeles · 发表于：The Lancet Oncology · 年份：2021 · DOI：10.1016/s1470-2045(21)00522-2 · 被引用次数：99 · 研究领域：Genetic factors in colorectal cancer、Prostate Cancer Diagnosis and Treatment、Prostate Cancer Treatment and Research

BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variant...