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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Study protocol

Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study

Authors: David Margel, Ofer Benjaminov, Rachel Ozalvo, Liat Shavit Grievink, Inbal Kedar, Rinat Yerushalmi, Irit Ben-Aharon, Victoria Neiman, Ofer Yossepowitch, Daniel Kedar, Zohar Levy, Mordechai Shohat, Baruch Brenner, Jack Baniel, Eli Rosenbaum

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Prostate cancer screening among the general population is highly debatable. Nevertheless, screening among high-risk groups is appealing. Prior data suggests that men carrying mutations in the BRCA1& 2 genes may be at increased risk of developing prostate cancer. Additionally, they appear to develop prostate cancer at a younger age and with a more aggressive course. However, prior studies did not systematically perform prostate biopsies and thus cannot determine the true prevalence of prostate cancer in this population.

Methods

This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40–70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention.

Discussion

The proposed research is highly translational and focuses not only on the clinical results, but on the future specimens that will be used to advance our understanding of prostate cancer patho-physiology. Most importantly, these high-risk germ-line mutation carriers are ideal candidates for primary and secondary prevention initiatives.

Trial registration

ClinicalTrials.gov: NCT02053805.
Appendix
Available only for authorised users
Literature
1.
Seigel R, Ward E, Brawley O, Jemal A: Cancer statistics, 2011. CA Cancer J Clin. 2011, 61: 212-236.CrossRef
2.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010, 127: 2893-2917.CrossRefPubMed
3.
4.
Messing EM, Albertsen P, Andriole GL, Carroll PR, Klein EA: The society of urologic oncology’s reply to the US preventative services task force’s recommendation on PSA testing. Urol Oncol. 2012, 30 (1): 117-119.CrossRefPubMed
5.
Kwiatkowski M, Klotz L, Hugosson J, Recker F: Comment on the US preventive services task force’s draft recommendation on screening for prostate cancer. Eur Urol. 2012, 61 (4): 851-854.CrossRefPubMed
6.
Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A, ERSPC Investigators: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009, 360: 1320-1328.CrossRefPubMed
7.
Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Páez A, Määttänen L, Bangma CH, Aus G, Carlsson S, Villers A, Rebillard X, van der Kwast T, Kujala PM, Blijenberg BG, Stenman UH, Huber A, Taari K, Hakama M, Moss SM, de Koning HJ, Auvinen A, ERSPC Investigators: Prostate-cancer mortality at 11 years of follow-up. N Engl J Med. 2012, 366 (11): 981-990.CrossRefPubMed
8.
Andriole GL, Crawford ED, Grubb RL, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, O’Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, Gohagan JK, Berg CD, PLCO Project Team: Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009, 360: 1310-1319.CrossRefPubMedPubMedCentral
9.
Djavan B, Waldert M, Zlotta A, Dobronski P, Seitz C, Remzi M, Borkowski A, Schulman C, Marberger M: Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study. J Urol. 2001, 166 (3): 856-860.CrossRefPubMed
10.
Rodríguez LV, Terris MK: Risks and complications of transrectal ultrasound guided prostate needle biopsy: a prospective study and review of the literature. J Urol. 1998, 160 (6 Pt 1): 2115-2120.PubMed
11.
Lee G, Attar K, Laniado M, Karim O: Safety and detailed patterns of morbidity of transrectal ultrasound guided needle biopsy of prostate in an urologist-led unit. Int Urol Nephrol. 2006, 38 (2): 281-285.CrossRefPubMed
12.
Bratt O: Hereditary prostate cancer: clinical aspects. J Urol Sep. 2002, 168 (3): 906-913.CrossRef
13.
Cooney KA, McCarthy JD, Lange E, Huang L, Miesfeldt S, Montie JE, Oesterling JE, Sandler HM, Lange K: Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study. J Natl Cancer Inst. 1997, 89 (13): 955-959.CrossRefPubMed
14.
Grönberg H, Isaacs SD, Smith JR, Carpten JD, Bova GS, Freije D, Xu J, Meyers DA, Collins FS, Trent JM, Walsh PC, Isaacs WB: Characteristics of prostate cancer in families potentially linked to the hereditary prostate cancer 1 (HPC1) locus. JAMA. 1997, 278 (15): 1251-1255.CrossRefPubMed
15.
Mitra AV, Bancroft EK, Barbachano Y, Page EC, Foster CS, Jameson C, Mitchell G, Lindeman GJ, Stapleton A, Suthers G, Evans DG, Cruger D, Blanco I, Mercer C, Kirk J, Maehle L, Hodgson S, Walker L, Izatt L, Douglas F, Tucker K, Dorkins H, Clowes V, Male A, Donaldson A, Brewer C, Doherty R, Bulman B, Osther PJ, et al: Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study. BJU Int. 2010, 107 (1): 28-39.CrossRefPubMed
16.
Tryggvadóttir L, Vidarsdóttir L, Thorgeirsson T, Jonasson JG, Olafsdóttir EJ, Olafsdóttir GH, Rafnar T, Thorlacius S, Jonsson E, Eyfjord JE, Tulinius H: Prostate cancer progression and survival in BRCA2 mutation carriers. J Natl Cancer Inst. 2007, 99 (12): 929-935.CrossRefPubMed
17.
Narod SA, Neuhausen S, Vichodez G, Armel S, Lynch HT, Ghadirian P, Cummings S, Olopade O, Stoppa-Lyonnet D, Couch F, Wagner T, Warner E, Foulkes WD, Saal H, Weitzel J, Tulman A, Poll A, Nam R, Sun P, Danquah J, Domchek S, Tung N, Ainsworth P, Horsman D, Kim-Sing C, Maugard C, Eisen A, Daly M, McKinnon W, Hereditary Breast Cancer Study Group, et al: Rapid progression of prostate cancer in men with a BRCA2 mutation. Br J Cancer. 2008, 99 (2): 371-374.CrossRefPubMedPubMedCentral
18.
Thorne H, Willems AJ, Niedermayr E, Hoh IM, Li J, Clouston D, Mitchell G, Fox S, Hopper JL, Bolton D, Kathleen Cunningham Consortium for Research in Familial Breast Cancer Consortium: Decreased prostate cancer-specific survival of men with BRCA2 mutations from multiple breast cancer families. Cancer Prev Res (Phila). 2011, 4: 1002-1010.CrossRef
19.
Gallagher DJ, Gaudet MM, Pal P, Kirchhoff T, Balistreri L, Vora K, Bhatia J, Stadler Z, Fine SW, Reuter V, Zelefsky M, Morris MJ, Scher HI, Klein RJ, Norton L, Eastham JA, Scardino PT, Robson ME, Offit K: Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res. 2010, 16: 2115-2121.CrossRefPubMedPubMedCentral
20.
Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, Mahmud N, Dadaev T, Govindasami K, Guy M, Sawyer E, Wilkinson R, Ardern-Jones A, Ellis S, Frost D, Peock S, Evans DG, Tischkowitz M, Cole T, Davidson R, Eccles D, Brewer C, Douglas F, Porteous ME, Donaldson A, Dorkins H, Izatt L, Cook J, Hodgson S, Kennedy MJ, et al: Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer. J Clin Oncol. 2013, 31 (14): 1748-1757.CrossRefPubMedPubMedCentral
21.
Thompson D, Easton D, Breast Cancer Linkage Consortium: Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002, 94 (18): 1358-1365.CrossRefPubMed
22.
Thompson D, Easton D, Breast Cancer Linkage Consortium: Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet. 2002, 68 (2): 410-419.CrossRef
23.
Edwards SM1, Kote-Jarai Z, Meitz J, Hamoudi R, Hope Q, Osin P, Jackson R, Southgate C, Singh R, Falconer A, Dearnaley DP, Ardern-Jones A, Murkin A, Dowe A, Kelly J, Williams S, Oram R, Stevens M, Teare DM, Ponder BA, Gayther SA, Easton DF, Eeles RA, Cancer Research UK/Bristish Prostate Group UK Familial Prostate Cancer Study Collaborators: Two percent of men with early-onset prostate cancer harbour germline mutations in the BRCA2 gene. Am J Hum Genet. 2003, 72 (1): 1-12.CrossRefPubMed
24.
25.
Le JD, Stephenson S, Brugger M, Lu DY, Lieu P, Sonn GA, Natarajan S, Dorey FJ, Huang J, Margolis DJ, Reiter RE, Marks LS: MRI-ultrasound fusion biopsy for prediction of final prostate pathology. J Urol. 2014, doi:10.1016/j.juro.2014.04.094. [Epub ahead of print]
26.
27.
Bancroft EK, Page EC, Castro E, Lilja H, Vickers A, Sjoberg D, Assel M, Foster CS, Mitchell G, Drew K, Mæhle L, Axcrona K, Evans DG, Bulman B, Eccles D, McBride D, van Asperen C, Vasen H, Kiemeney LA, Ringelberg J, Cybulski C, Wokolorczyk D, Selkirk C, Hulick PJ, Bojesen A, Skytte AB, Lam J, Taylor L, Oldenburg R, Cremers R, et al: Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur Urol 2014 doi.org/10.1016/j.eururo.2014.01.003
28.
Alonzo TA, Brinton JT, Ringham BM, Glueck DH: Bias in estimating accuracy of a binary screening test with differential disease verification. Stat Med. 2011, 30 (15): 1852-64. doi: 10.1002/sim.4232CrossRefPubMedPubMedCentral
29.
Walter SD, Macaskill P, Lord SJ, Irwig L: Effect of dependent errors in the assessment of diagnostic or screening test accuracy when the reference standard is imperfect. Stat Med. 2012, 31 (11–12): 1129-38. doi:10.1002/sim.4444CrossRefPubMed
30.
Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA: The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003, 349 (3): 215-24.CrossRefPubMed
31.
Mulligan AM, Couch FJ, Barrowdale D, Domchek SM, Eccles D, Nevanlinna H, Ramus SJ, Robson M, Sherman M, Spurdle AB, Wappenschmidt B, Lee A, McGuffog L, Healey S, Sinilnikova OM, Janavicius R, Hansen T, Nielsen FC, Ejlertsen B, Osorio A, Muñoz-Repeto I, Durán M, Godino J, Pertesi M, Benítez J, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Cattaneo E, et al: Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the consortium of investigators of modifiers of BRCA1/2. Breast Cancer Res. 2011, 13 (6): R110-doi:10.1186/bcr3052CrossRefPubMedPubMedCentral
32.
Ferla R, Calò V, Cascio S, Rinaldi G, Badalamenti G, Carreca I, Surmacz E, Colucci G, Bazan V, Russo A: Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007, 6: vi93-8-
Metadata
Title
Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study
Authors
David Margel
Ofer Benjaminov
Rachel Ozalvo
Liat Shavit Grievink
Inbal Kedar
Rinat Yerushalmi
Irit Ben-Aharon
Victoria Neiman
Ofer Yossepowitch
Daniel Kedar
Zohar Levy
Mordechai Shohat
Baruch Brenner
Jack Baniel
Eli Rosenbaum
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-528

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