Targeted Prostate Cancer Screening in Carriers of BRCA1 or BRCA2 Pathogenic Germline Variants Detects Clinically Relevant Disease: 5-year Results from the IMPACT Study.
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Bancroft Elizabeth K, Page Elizabeth C, McHugh Jana, Thomas Sarah, Taylor Natalie, Pope Jennifer, Evans D Gareth, Rothwell Jeanette, Grindedal Eli Marie, Maehle Lovise, James Paul, McKinley Joanne, Mascarenhas Lyon, Side Lucy, Thomas Tessy, van Leerdam Monique E, van Asperen Christi J, Kiemeney Lambertus A L M, Ringelberg Janneke, Vlaming Michiel, Rønlund Karina, Osther Palle J S, Helfand Brian T, Hutten Christina G, Oldenburg Rogier A, Cybulski Cezary, Wokolorczyk Dominika, Ong Kai-Ren, Huber Camilla, Salinas Monica, Feliubadaló Lidia, Oosterwijk Jan C, van Zelst-Stams Wendy A G, Cook Jackie, Rosario Derek J, Maxwell Kara, Powers Jacquelyn, Buys Saundra, Lyman Jo, Ausems Margreet G E M, Schmutzler Rita K, Rhiem Kerstin, Izatt Louise, Tripathi Vishakha, Teixeira Manuel R, Cardoso Marta, Foulkes William D, Aprikian Armen, Davidson Rosemarie, Longmuir Mark, Ruijs Mariëlle W G, Blom Eveline W, van Engelen Klaartje, Williams Rachel, Andrews Lesley, Murphy Declan G, Saya Sibel, Halliday Dorothy, Walker Lisa, Liljegren Annelie, Carlsson Stefan, Azzabi Ashraf, Jobson Irene, Snape Katie, Gowie Merrie, Harris Marion, Tischkowitz Marc, Taylor Amy, Kirk Judy, Susman Rachel, Chen-Shtoyerman Rakefet, Spigelman Allan, Pachter Nicholas, Ahmed Munaza, Cajal Teresa Ramon Y, Krajc Mateja, Cleaver Ruth, Cruellas Mara, Perez-Ballestero Eduard, Brady Angela F, Gallagher David, Donaldson Alan, Barwell Julian, Nicolai Nicola, Friedman Eitan, Hall Michael J, Greenhalgh Lynn, Murthy Vedang, Copakova Lucia, McGrath John S, Cooke Peter, Arun Banu, Myhill Kathryn, Hogben Matthew, Hussain Syed, Aaronson Neil K, Ardern-Jones Audrey, Bangma Chris H, Castro Elena, Dearnaley David, Eccles Diana M, Tricker Karen, Falconer Alison, Gronberg Henrik, Hamdy Freddie C, Khoo Vincent, Lilja Hans, Lindeman Geoffrey J, Lubinski Jan, Axcrona Karol, Mikropoulos Christos, Mitra Anita, Offman Judith, Rennert Gad, Suri Mohnish, Dudderidge Tim, IMPACT Study Collaborators, Brook Mark N, Kote-Jarai Zsofia, Eeles Rosalind A
Аннотация
METHODS: Between 2005 and 2015, 3063 participants aged 40-69 yr (median 54 yr) were recruited from 65 centres in 20 countries in two cohorts: (1) BRCA1/BRCA2 PGV carriers (915 BRCA1, 901 BRCA2); and (2) age-matched noncarriers for a familial PGV (727 BRCA1 and 520 BRCA2 noncarriers). Annual PSA screening was performed, with PSA >3.0 ng/ml used as the indication for prostate biopsy. Our aim was to identify differences by PGV status in (1) the incidence of PC and of clinically significant PC (csPC; grade group ≥2) and (2) tumour stage and characteristics after five screening rounds.
KEY FINDINGS AND LIMITATIONS: There was no statistically significant difference in PC incidence between BRCA1/BRCA2 PGV carriers and noncarriers. csPC incidence was significantly higher for BRCA2 PGV carriers than for noncarriers (3.1% vs 1.3%; p = 0.04). Among men with PC, the proportion of tumours with National Comprehensive Cancer Network intermediate unfavourable/high risk was higher in the BRCA1/BRCA2 PGV groups versus the corresponding group without PGVs (BRCA2: 65% vs 32%, p = 0.029; BRCA1: 56% vs 18%, p = 0.0017). There were no T4 or metastatic PC cases. Pathology after radical prostatectomy revealed tumour upgrading for 7/23 (26%) BRCA1 PGV carriers and 10/34 (26%) BRCA2 PGV carriers, with no tumour upgrading for men without PGVs. Study limitations include the biopsy compliance rate and changes in PC diagnostic pathways since 2005.
CONCLUSIONS AND CLINICAL IMPLICATIONS: Annual PSA screening in BRCA2 PGV carriers confirmed a higher incidence of csPC and detection of clinically relevant tumours in comparison to noncarriers. For the first time, we confirm that PSA screening in BRCA1 PGV carriers results in early detection of NCCN IR-U/HR PC. Systematic PSA screening is recommended for BRCA2 PGV carriers and should be considered for BRCA1 PGV carriers.