title: The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Castro
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Christos
authors.initials: C
authors.lastname: Mikropoulos
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Bancroft
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Tokhir
authors.initials: T
authors.lastname: Dadaev
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Chee
authors.initials: C
authors.lastname: Goh
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Taylor
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Edward
authors.initials: E
authors.lastname: Saunders
authors.affiliation: Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Borley
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Diana
authors.initials: D
authors.lastname: Keating
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Page
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Sibel
authors.initials: S
authors.lastname: Saya
authors.affiliation: Histopathology Department, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hazell
authors.affiliation: Histopathology Department, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Naomi
authors.initials: N
authors.lastname: Livni
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Nandita
authors.initials: N
authors.lastname: deSouza
authors.affiliation: Department of Oncology, Cancer Research UK Cambridge Institute, Cambridge, United Kingdom Department of Surgery, Cancer Research UK Cambridge Institute, Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Neal
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Pardeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom Academic Urology Unit, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom ros.eeles@icr.ac.uk.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging; D055088:Early Detection of Cancer; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: D017430:Prostate-Specific Antigen
keywords: Family history; Prostate cancer; Prostate-specific antigen; Single nucleotide polymorphisms