The profile feasibility study

Targeted screening of men with a family history of prostate cancer

Elena Castro, Christos Mikropoulos, Elizabeth K. Bancroft, Tokhir Dadaev, Chee Goh, Natalie Z Taylor, Edward J. Saunders, Nigel Borley, Diana Keating, Elizabeth C. Page, Sibel Saya, Stephen Hazell, Naomi Livni, Nandita Desouza, David Neal, Freddie C Hamdy, Pardeep Kumar, Antonis C Antoniou, Zsofia Kote-Jarai, Rosalind A Eeles & 13 others A. Ardern-Jones, P. Ardern-Jones, Nicholas Van As, David P Dearnaley, Caroline Foster, V. Khoo, S. Lewis, Hans Lilja, Thomas J Melia, C. Moynihan, Paul D P Pharoah, A. Sohaib, The Profile Study Steering Committee

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Background. 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. Patients and Methods. 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. Results. 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 5 .00004, respectively). Conclusion. 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.

Original languageEnglish
Pages (from-to)716-722
Number of pages7
JournalOncologist
Volume21
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016
Externally publishedYes

Keywords

  • Family history
  • Prostate cancer
  • Prostate-specific antigen
  • Single nucleotide polymorphisms

Cite this

Castro, E., Mikropoulos, C., Bancroft, E. K., Dadaev, T., Goh, C., Taylor, N. Z., ... The Profile Study Steering Committee (2016). The profile feasibility study: Targeted screening of men with a family history of prostate cancer. Oncologist, 21(6), 716-722. https://doi.org/10.1634/theoncologist.2015-0336
Castro, Elena ; Mikropoulos, Christos ; Bancroft, Elizabeth K. ; Dadaev, Tokhir ; Goh, Chee ; Taylor, Natalie Z ; Saunders, Edward J. ; Borley, Nigel ; Keating, Diana ; Page, Elizabeth C. ; Saya, Sibel ; Hazell, Stephen ; Livni, Naomi ; Desouza, Nandita ; Neal, David ; Hamdy, Freddie C ; Kumar, Pardeep ; Antoniou, Antonis C ; Kote-Jarai, Zsofia ; Eeles, Rosalind A ; Ardern-Jones, A. ; Ardern-Jones, P. ; Van As, Nicholas ; Dearnaley, David P ; Foster, Caroline ; Khoo, V. ; Lewis, S. ; Lilja, Hans ; Melia, Thomas J ; Moynihan, C. ; Pharoah, Paul D P ; Sohaib, A. ; The Profile Study Steering Committee. / The profile feasibility study : Targeted screening of men with a family history of prostate cancer. In: Oncologist. 2016 ; Vol. 21, No. 6. pp. 716-722.
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abstract = "Background. 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. Patients and Methods. 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. Results. 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 5 .00004, respectively). Conclusion. 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.",
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author = "Elena Castro and Christos Mikropoulos and Bancroft, {Elizabeth K.} and Tokhir Dadaev and Chee Goh and Taylor, {Natalie Z} and Saunders, {Edward J.} and Nigel Borley and Diana Keating and Page, {Elizabeth C.} and Sibel Saya and Stephen Hazell and Naomi Livni and Nandita Desouza and David Neal and Hamdy, {Freddie C} and Pardeep Kumar and Antoniou, {Antonis C} and Zsofia Kote-Jarai and Eeles, {Rosalind A} and A. Ardern-Jones and P. Ardern-Jones and {Van As}, Nicholas and Dearnaley, {David P} and Caroline Foster and V. Khoo and S. Lewis and Hans Lilja and Melia, {Thomas J} and C. Moynihan and Pharoah, {Paul D P} and A. Sohaib and {The Profile Study Steering Committee}",
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Castro, E, Mikropoulos, C, Bancroft, EK, Dadaev, T, Goh, C, Taylor, NZ, Saunders, EJ, 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, Eeles, RA, Ardern-Jones, A, Ardern-Jones, P, Van As, N, Dearnaley, DP, Foster, C, Khoo, V, Lewis, S, Lilja, H, Melia, TJ, Moynihan, C, Pharoah, PDP, Sohaib, A & The Profile Study Steering Committee 2016, 'The profile feasibility study: Targeted screening of men with a family history of prostate cancer', Oncologist, vol. 21, no. 6, pp. 716-722. https://doi.org/10.1634/theoncologist.2015-0336

The profile feasibility study : Targeted screening of men with a family history of prostate cancer. / Castro, Elena; Mikropoulos, Christos; Bancroft, Elizabeth K.; Dadaev, Tokhir; Goh, Chee; Taylor, Natalie Z; Saunders, Edward J.; Borley, Nigel; Keating, Diana; Page, Elizabeth C.; Saya, Sibel; Hazell, Stephen; Livni, Naomi; Desouza, Nandita; Neal, David; Hamdy, Freddie C; Kumar, Pardeep; Antoniou, Antonis C; Kote-Jarai, Zsofia; Eeles, Rosalind A; Ardern-Jones, A.; Ardern-Jones, P.; Van As, Nicholas; Dearnaley, David P; Foster, Caroline; Khoo, V.; Lewis, S.; Lilja, Hans; Melia, Thomas J; Moynihan, C.; Pharoah, Paul D P; Sohaib, A.; The Profile Study Steering Committee.

In: Oncologist, Vol. 21, No. 6, 01.06.2016, p. 716-722.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The profile feasibility study

T2 - Targeted screening of men with a family history of prostate cancer

AU - Castro, Elena

AU - Mikropoulos, Christos

AU - Bancroft, Elizabeth K.

AU - Dadaev, Tokhir

AU - Goh, Chee

AU - Taylor, Natalie Z

AU - Saunders, Edward J.

AU - Borley, Nigel

AU - Keating, Diana

AU - Page, Elizabeth C.

AU - Saya, Sibel

AU - Hazell, Stephen

AU - Livni, Naomi

AU - Desouza, Nandita

AU - Neal, David

AU - Hamdy, Freddie C

AU - Kumar, Pardeep

AU - Antoniou, Antonis C

AU - Kote-Jarai, Zsofia

AU - Eeles, Rosalind A

AU - Ardern-Jones, A.

AU - Ardern-Jones, P.

AU - Van As, Nicholas

AU - Dearnaley, David P

AU - Foster, Caroline

AU - Khoo, V.

AU - Lewis, S.

AU - Lilja, Hans

AU - Melia, Thomas J

AU - Moynihan, C.

AU - Pharoah, Paul D P

AU - Sohaib, A.

AU - The Profile Study Steering Committee

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Background. 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. Patients and Methods. 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. Results. 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 5 .00004, respectively). Conclusion. 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.

AB - Background. 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. Patients and Methods. 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. Results. 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 5 .00004, respectively). Conclusion. 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.

KW - Family history

KW - Prostate cancer

KW - Prostate-specific antigen

KW - Single nucleotide polymorphisms

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U2 - 10.1634/theoncologist.2015-0336

DO - 10.1634/theoncologist.2015-0336

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JF - Oncologist

SN - 1083-7159

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