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Br J Cancer. 2018 Jan;118(2):266-276. doi: 10.1038/bjc.2017.429. Epub 2018 Jan 4.

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

Mikropoulos C1, Selkirk CGH2,3, Saya S1, Bancroft E1,4, Vertosick E5, Dadaev T1, Brendler C2, Page E1, Dias A1,4, Evans DG6, Rothwell J6, Maehle L7, Axcrona K8, Richardson K9,10, Eccles D11,12, Jensen T13, Osther PJ13, van Asperen CJ14, Vasen H15, Kiemeney LA16, Ringelberg J15, Cybulski C17, Wokolorczyk D17, Hart R18, Glover W18, Lam J19, Taylor L19, Salinas M20, Feliubadaló L20, Oldenburg R21, Cremers R16, Verhaegh G16, van Zelst-Stams WA15, Oosterwijk JC22, Cook J23, Rosario DJ24, Buys SS25, Conner T25, Domchek S26, Powers J26, Ausems MG27, Teixeira MR28,29, Maia S28, Izatt L30, Schmutzler R31, Rhiem K31, Foulkes WD32, Boshari T32, Davidson R33, Ruijs M34, Helderman-van den Enden AT35, Andrews L36, Walker L37, Snape K38, Henderson A39, Jobson I39, Lindeman GJ40,41,42, Liljegren A43, Harris M44, Adank MA45, Kirk J46,47, Taylor A48, Susman R49, Chen-Shtoyerman R50, Pachter N51,52, Spigelman A53,54,55, Side L56, Zgajnar J57, Mora J58, Brewer C59,60, Gadea N61, Brady AF62, Gallagher D63, van Os T64, Donaldson A65, Stefansdottir V66, Barwell J67,68, James PA9,10,69, Murphy D10, Friedman E70,71, Nicolai N72, Greenhalgh L73, Obeid E74, Murthy V75, Copakova L76, McGrath J60, Teo SH77, Strom S78, Kast K79,80,81, Leongamornlert DA1, Chamberlain A1, Pope J1, Newlin AC3, Aaronson N34, Ardern-Jones A4, Bangma C21, Castro E82, Dearnaley D1,4, Eyfjord J83, Falconer A84, Foster CS85, Gronberg H86, Hamdy FC37,87, Johannsson O66, Khoo V4, Lubinski J17, Grindedal EM7, McKinley J9, Shackleton K40, Mitra AV88, Moynihan C1, Rennert G89, Suri M90, Tricker K6; IMPACT study collaborators, Moss S91, Kote-Jarai Z1, Vickers A5, Lilja H87,92, Helfand BT2, Eeles RA1,4.

Author information

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
Center for Medical Genetics, Department of Medicine, NorthShore University HealthSystem, Evanston, IL 60201, USA.
4
Royal Marsden NHS Foundation Trust, Fulham Rd, London SW3 6JJ, UK.
5
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
6
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.
7
Department of Medical Genetics, Oslo University Hospital, Oslo 0372, Norway.
8
Akershus University Hospital, Lørenskog 1478, Norway.
9
Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, VIC 3000, Australia.
10
The Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia.
11
Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK.
12
Cancer Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
13
Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark.
14
Leiden University Medical Center, Department of Clinical Genetics, Leiden, ZA 2333, The Netherlands.
15
Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, ZA 2333, The Netherlands.
16
Radboud University Medical Center, Nijmegen, GA 6525, The Netherlands.
17
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-204, Poland.
18
Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham B15 2TG, UK.
19
Department of Urology, Repatriation General Hospital, Daw Park, SA 5041, Australia.
20
Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL, CIBERONC), L'Hospitalet de Llobregat, Barcelona 08908, Spain.
21
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands.
22
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, The Netherlands.
23
Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, UK.
24
Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
25
Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84103, USA.
26
Basser Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
27
Department of Genetics, University Medical Centre Utrecht, Utrecht, CX, The Netherlands.
28
Genetics Department and Research Center, Portuguese Oncology Institute, Porto 4200-072, Portugal.
29
Biomedical Sciences Institute (ICBAS), Porto University, Porto 4200-072, Portugal.
30
South East Thames Genetics Service, Guy's Hospital, London SE1 9RT, UK.
31
Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne 50937, Germany.
32
McGill Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.
33
Duncan Guthrie Institute of Medical Genetics, Yorkhill NHS Trust, Glasgow G38SJ, UK.
34
The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands.
35
Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, HX 6229, The Netherlands.
36
Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, NSW 2031, Australia.
37
Churchill Hospital, Headington, Oxford OX3 7LE, UK.
38
St George's Hospital, Tooting, London SW17 0QT, UK.
39
Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle NE1 3BZ, UK.
40
Parkville Familial Cancer Centre, The Royal Melbourne Hospital, Grattan St, Parkville, VIC 3050, Australia.
41
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia.
42
Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia.
43
Karolinska University Hospital and Karolinska Institutet, Solna 171 77, Sweden.
44
Familial Cancer Centre, Monash Health, Clayton, VIC 3168, Australia.
45
VU University Medical Center, Amsterdam 1081 HV, The Netherlands.
46
Familial Cancer Service, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia.
47
Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Sydney, NSW 2155, Australia.
48
Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
49
Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, QLD 4029, Australia.
50
The Genetic Institute, Kaplan Medical Center, Rehovot 76100, Israel.
51
Genetic Services of WA, King Edward Memorial Hospital, Subiaco, WA 6008, Australia.
52
School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6009, Australia.
53
Hunter Family Cancer Service, Waratah, NSW 2298, Australia.
54
University of New South Wales, St Vincent's Clinical School, NSW 2052, Australia.
55
The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW 2010, Australia.
56
NE Thames Regional Genetics Service, Great Ormond St Hospital & UCL Institute of Women's Health, London WC1N 3JH, UK.
57
Institute of Oncology, Ljubljana 1000, Slovenia.
58
Hospital de Sant Pau, Barcelona 08041, Spain.
59
Peninsular Genetics, Derriford Hospital, Plymouth PL6 8DH, UK.
60
Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK.
61
High Risk and Cancer Prevention Clinic, Vall d'Hebron University Hospital, Barcelona 08035, Spain.
62
North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, London HA1 3UJ, UK.
63
St James' Hospital, Dublin 8, Ireland.
64
Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.
65
St Michael's Hospital, Bristol BS2 8EG, UK.
66
Landspitali-the National University Hospital of Iceland, Reykjavik 101, Iceland.
67
University of Leicester, Leicester LE1 7RH, UK.
68
University Hospitals Leicester, Leicester LE1 5WW, UK.
69
Genetic Medicine, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.
70
Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
71
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel.
72
Istituto Nazionale dei Tumori, Milano 20133, Italy.
73
Cheshire and Mersey Clinical Genetics Service, Liverpool Women's Hospital, Liverpool L8 7SS, UK.
74
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
75
Tata Memorial Centre, Mumbai, Maharashtra 400012, India.
76
National Cancer Institute, Bratislava 83310, Slovak Republic.
77
Cancer Research Initiatives Foundation, Subang Jaya Medical Centre, Subang Jaya, Selangor 47500, Darul Ehsan, Malaysia.
78
The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
79
Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01069, Germany.
80
National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden 01307, Germany.
81
German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
82
Prostate Cancer Unit, Spanish National Cancer Research Centre, Madrid 28029, Spain.
83
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik 101, Iceland.
84
Imperial College Healthcare NHS Trust, London, London W2 1NY, UK.
85
HCA Healthcare Laboratories, London WC1E 6JA, UK.
86
University Hospital, Umea 907 37, Sweden.
87
Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 2JD, UK.
88
University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK.
89
CHS National Cancer Control Center, Carmel Medical Center, Haifa 3436212, Israel.
90
Nottingham City Hospital, Nottingham NG5 1PB, UK.
91
Centre for Cancer Prevention, Queen Mary University of London, London EC1M 6BQ.
92
Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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.

PMID:
29301143
PMCID:
PMC5785754
DOI:
10.1038/bjc.2017.429
[Indexed for MEDLINE]
Free PMC Article

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