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The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer.

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Publication Date
2016-06
ICR Author
Eeles, Rosalind
Kote-Jarai, Zsofia
deSouza, Nandita
Saunders, Edward
Kumar, Pardeep
Dearnaley, David
Author
Castro, E
Mikropoulos, C
Bancroft, EK
Dadaev, T
Goh, C
Taylor, N
Saunders, E
Borley, N
Keating, D
Page, EC
Saya, S
Hazell, S
Livni, N
deSouza, N
Neal, D
Hamdy, FC
Kumar, P
Antoniou, AC
Kote-Jarai, Z
PROFILE Study Steering Committee
Eeles, RA
Type
Journal Article
Metadata
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Abstract
<h4>Background</h4>A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population.<h4>Patients and methods</h4>A total of 100 men aged 40-69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression.<h4>Results</h4>Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively).<h4>Conclusion</h4>The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress.<h4>Implications for practice</h4>Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.
URL
https://repository.icr.ac.uk/handle/internal/231
Collections
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
  • Closed Research Teams
Version of record
10.1634/theoncologist.2015-0336
Subject
PROFILE Study Steering Committee
Prostate
Humans
Prostatic Neoplasms
Prostate-Specific Antigen
Diffusion Magnetic Resonance Imaging
Biopsy
Cross-Sectional Studies
Feasibility Studies
Pilot Projects
Polymorphism, Single Nucleotide
Adult
Aged
Middle Aged
Male
Early Detection of Cancer
Research team
Clinical Academic Radiotherapy (Dearnaley)
Magnetic Resonance
Oncogenetics
Language
eng
Date accepted
2016-02-09
License start date
2016-06
Citation
The oncologist, 2016, 21 (6), pp. 716 - 722

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