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Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Mikropoulos C 1 , Selkirk CGH 2 , Saya S 1 , Bancroft E 1 , Vertosick E 3 , Dadaev T 1 Show all authors , Brendler C 2 , Page E 1 , Dias A 1 , Evans DG 4 , Rothwell J 4 , Maehle L 5 , Axcrona K 6 , Richardson K 7 , Eccles D 8 , Jensen T 9 , Osther PJ 9 , van Asperen CJ 10 , Vasen H 11 , Kiemeney LA 12 , Ringelberg J 11 , Cybulski C 13 , Wokolorczyk D 13 , Hart R 14 , Glover W 14 , Lam J 15 , Taylor L 15 , Salinas M 16 , Feliubadaló L 16 , Oldenburg R 17 , Cremers R 12 , Verhaegh G 12 , van Zelst-Stams WA 11 , Oosterwijk JC 18 , Cook J 19 , Rosario DJ 20 , Buys SS 21 , Conner T 21 , Domchek S 22 , Powers J 22 , Ausems MG 23 , Teixeira MR 24 , Maia S 24 , Izatt L 25 , Schmutzler R 26 , Rhiem K 26 , Foulkes WD 27 , Boshari T 27 , Davidson R 28 , Ruijs M 29 , Helderman-van den Enden AT 30 , Andrews L 31 , Walker L 32 , Snape K 33 , Henderson A 34 , Jobson I 34 , Lindeman GJ 35 , Liljegren A 36 , Harris M 37 , Adank MA 38 , Kirk J 39 , Taylor A 40 , Susman R 41 , Chen-Shtoyerman R 42 , Pachter N 43 , Spigelman A 44 , Side L 45 , Zgajnar J 46 , Mora J 47 , Brewer C 48 , Gadea N 49 , Brady AF 50 , Gallagher D 51 , van Os T 52 , Donaldson A 53 , Stefansdottir V 54 , Barwell J 55 , James PA 7 , Murphy D 56 , Friedman E 57 , Nicolai N 58 , Greenhalgh L 59 , Obeid E 60 , Murthy V 61 , Copakova L 62 , McGrath J 63 , Teo SH 64 , Strom S 65 , Kast K 66 , Leongamornlert DA 1 , Chamberlain A 1 , Pope J 1 , Newlin AC 67 , Aaronson N 29 , Ardern-Jones A 68 , Bangma C 17 , Castro E 69 , Dearnaley D 1 , Eyfjord J 70 , Falconer A 71 , Foster CS 72 , Gronberg H 73 , Hamdy FC 32 , Johannsson O 54 , Khoo V 68 , Lubinski J 13 , Grindedal EM 5 , McKinley J 7 , Shackleton K 35 , Mitra AV 74 , Moynihan C 1 , Rennert G 75 , Suri M 76 , Tricker K 4 , IMPACT study collaborators , Moss S 77 , Kote-Jarai Z 1 , Vickers A 3 , Lilja H 78 , Helfand BT 2 , Eeles RA 1

Affiliations 

  • 1 The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
  • 2 The John and Carol Walter Center for Urological Health, Department of Surgery, North Shore University Health System, Evanston, IL 60201, USA
  • 3 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
  • 4 Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK
  • 5 Department of Medical Genetics, Oslo University Hospital, Oslo 0372, Norway
  • 6 Akershus University Hospital, Lørenskog 1478, Norway
  • 7 Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, VIC 3000, Australia
  • 8 Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK
  • 9 Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark
  • 10 Leiden University Medical Center, Department of Clinical Genetics, Leiden, ZA 2333, The Netherlands
  • 11 Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, ZA 2333, The Netherlands
  • 12 Radboud University Medical Center, Nijmegen, GA 6525, The Netherlands
  • 13 International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-204, Poland
  • 14 Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham B15 2TG, UK
  • 15 Department of Urology, Repatriation General Hospital, Daw Park, SA 5041, Australia
  • 16 Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL, CIBERONC), L'Hospitalet de Llobregat, Barcelona 08908, Spain
  • 17 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands
  • 18 Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, The Netherlands
  • 19 Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, UK
  • 20 Royal Hallamshire Hospital, Sheffield S10 2JF, UK
  • 21 Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84103, USA
  • 22 Basser Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA
  • 23 Department of Genetics, University Medical Centre Utrecht, Utrecht, CX, The Netherlands
  • 24 Genetics Department and Research Center, Portuguese Oncology Institute, Porto 4200-072, Portugal
  • 25 South East Thames Genetics Service, Guy's Hospital, London SE1 9RT, UK
  • 26 Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne 50937, Germany
  • 27 McGill Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada
  • 28 Duncan Guthrie Institute of Medical Genetics, Yorkhill NHS Trust, Glasgow G38SJ, UK
  • 29 The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands
  • 30 Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, HX 6229, The Netherlands
  • 31 Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, NSW 2031, Australia
  • 32 Churchill Hospital, Headington, Oxford OX3 7LE, UK
  • 33 St George's Hospital, Tooting, London SW17 0QT, UK
  • 34 Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle NE1 3BZ, UK
  • 35 Parkville Familial Cancer Centre, The Royal Melbourne Hospital, Grattan St, Parkville, VIC 3050, Australia
  • 36 Karolinska University Hospital and Karolinska Institutet, Solna 171 77, Sweden
  • 37 Familial Cancer Centre, Monash Health, Clayton, VIC 3168, Australia
  • 38 VU University Medical Center, Amsterdam 1081 HV, The Netherlands
  • 39 Familial Cancer Service, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia
  • 40 Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
  • 41 Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, QLD 4029, Australia
  • 42 The Genetic Institute, Kaplan Medical Center, Rehovot 76100, Israel
  • 43 Genetic Services of WA, King Edward Memorial Hospital, Subiaco, WA 6008, Australia
  • 44 Hunter Family Cancer Service, Waratah, NSW 2298, Australia
  • 45 NE Thames Regional Genetics Service, Great Ormond St Hospital & UCL Institute of Women's Health, London WC1N 3JH, UK
  • 46 Institute of Oncology, Ljubljana 1000, Slovenia
  • 47 Hospital de Sant Pau, Barcelona 08041, Spain
  • 48 Peninsular Genetics, Derriford Hospital, Plymouth PL6 8DH, UK
  • 49 High Risk and Cancer Prevention Clinic, Vall d'Hebron University Hospital, Barcelona 08035, Spain
  • 50 North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, London HA1 3UJ, UK
  • 51 St James' Hospital, Dublin 8, Ireland
  • 52 Academic Medical Center, Amsterdam 1105 AZ, The Netherlands
  • 53 St Michael's Hospital, Bristol BS2 8EG, UK
  • 54 Landspitali-the National University Hospital of Iceland, Reykjavik 101, Iceland
  • 55 University of Leicester, Leicester LE1 7RH, UK
  • 56 The Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia
  • 57 Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel
  • 58 Istituto Nazionale dei Tumori, Milano 20133, Italy
  • 59 Cheshire and Mersey Clinical Genetics Service, Liverpool Women's Hospital, Liverpool L8 7SS, UK
  • 60 Fox Chase Cancer Center, Philadelphia, PA 19111, USA
  • 61 Tata Memorial Centre, Mumbai, Maharashtra 400012, India
  • 62 National Cancer Institute, Bratislava 83310, Slovak Republic
  • 63 Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK
  • 64 Cancer Research Initiatives Foundation, Subang Jaya Medical Centre, Subang Jaya, Selangor 47500, Darul Ehsan, Malaysia
  • 65 The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
  • 66 Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01069, Germany
  • 67 Center for Medical Genetics, Department of Medicine, NorthShore University HealthSystem, Evanston, IL 60201, USA
  • 68 Royal Marsden NHS Foundation Trust, Fulham Rd, London SW3 6JJ, UK
  • 69 Prostate Cancer Unit, Spanish National Cancer Research Centre, Madrid 28029, Spain
  • 70 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik 101, Iceland
  • 71 Imperial College Healthcare NHS Trust, London, London W2 1NY, UK
  • 72 HCA Healthcare Laboratories, London WC1E 6JA, UK
  • 73 University Hospital, Umea 907 37, Sweden
  • 74 University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK
  • 75 CHS National Cancer Control Center, Carmel Medical Center, Haifa 3436212, Israel
  • 76 Nottingham City Hospital, Nottingham NG5 1PB, UK
  • 77 Centre for Cancer Prevention, Queen Mary University of London, London EC1M 6BQ
  • 78 Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 2JD, UK
Br J Cancer, 2018 Jan;118(2):266-276.
PMID: 29301143 DOI: 10.1038/bjc.2017.429

Abstract

BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.

METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.

RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.

CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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