The PROFILE Study: Understanding why some men are at higher risk of prostate cancer
The PROFILE study aims to understand why some men, including black men, are at greater risk of prostate cancer.
Understanding the genetics that influence risk of prostate cancer could improve the way we screen men for prostate cancer in future, and help more men get diagnosed and treated early.
This video was created in partnership with the men and the PROFILE team in an involvement project led by Dr Emma Hainsworth. It was funded by a patient and public involvement and engagement grant from the NIHR Biomedical Research Centre at The Royal Marsden and the ICR.
The PROFILE study is currently recruiting men aged 40-69 years who are at greater risk of prostate cancer, including men of African or African-Caribbean ancestry, men with genetic mutations known to increase their risk and men of European ancestry with a positive family history of prostate cancer.
You can read more about who is eligible for the study below.
For more information, please contact the PROFILE Study Team:
Tel: 0208 722 4483
Email: [email protected]
Information for Clinicians
The PROFILE Study: Germline genetic profiling: correlation with targeted prostate cancer screening and treatment
Prostate cancer is now the commonest cancer in men in the Western world, with over 49,000 new cases diagnosed each year and a lifetime risk of 1 in 11 in the United Kingdom. Prostate cancer (PrCa) can run in some families and research studies have identified several genetic changes in populations of European ancestry that are thought to increase the risk of developing prostate cancer. Other studies have shown that men from certain ethnic groups also have a higher risk of prostate cancer, and this includes men of black African or Caribbean descent.
This study aims to look at men with a higher risk of prostate cancer based on their ethnicity or family history to see whether any of these genetic changes are present in their DNA (genetic material) and whether this could be a helpful screening tool in prostate cancer screening programmes. It is thought that many genetic changes are involved in the development of prostate cancer and research is being carried out worldwide to identify these genetic changes.
Some of these changes may cause a very slight increase in prostate cancer risk while others may cause a much larger increase in risk of developing prostate cancer. The investigators will invite: (i) men of European ancestry with a family history of prostate cancer; (ii) men of black African or Afro-Caribbean descent; and (iii) men of any ethnicity who have been found to have inherited a gene mutation that increases risk of prostate cancer, for targeted prostate screening (Prostate Specific Antigen (PSA) testing, MRI and a biopsy of the prostate gland) and genetic profiling.
The outcome of these prostate cancer screening investigations will be compared with the genetic profiles of those taking part in the study in order to look for certain genetic changes in the gene code that are thought to increase prostate cancer risk. This research will help us to determine what the role of such genetic profiling is in a prostate cancer screening programme and if it helps identify men at high prostate cancer risk.
The aim of the PROFILE study is to investigate the role of targeted prostate cancer screening in men at a genetically higher risk to estimate the incidence of prostate cancer and the sensitivity and specificity of PSA screening in these populations and correlate this with genetic profiles and biological endpoints. Additionally, the study aims to identify biomarkers from biological samples (such as blood and urine) as well as imaging technologies (e.g. MRI and new imaging techniques) as predictive markers of the risk of developing prostate cancer and to correlate these with genetic risk. This study has been designed using an observational approach to look at the correlation of cancer incidence (on biopsy) with genetic profile.
Three cohorts will be recruited:
- Men of European ancestry with family history of prostate cancer.
- Men of black African or Afro-Caribbean descent.
- Men of any ethnicity who have been found to have inherited a gene mutation that increases risk of prostate cancer (i.e. high-risk gene mutation).
Men with no prior screening will be offered immediate biopsy and genetic profiling. This will provide data on genetic profiling and correlation with biopsy irrespective of PSA in men who have not had any previous screening.
A PSA screening algorithm was considered as an alternative to biopsy but there is great controversy over the PSA threshold that should be used as a cut-off. Recent data have shown that a considerable percentage of men with a PSA within normal range have cancer at biopsy. Therefore, it was decided by the Steering Committee that all participants should be offered a biopsy within this study. This will tell us the acceptability of this approach.
Some men may opt not to have biopsy at baseline (i.e. initial stage). These men will be followed up with annual PSA, whereby prostate biopsy would be offered if PSA is above or equal to 1.0ng/ml if the man is aged under 50 years, or where PSA is above or equal to 2.0ng/ml if the man is aged fifty years or over.
Eligibility and recruitment
(1) Men of European ancestry with a positive family history of prostate cancer defined as:
- Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven prostate cancer diagnosed at <70 years
- Men with two relatives on the same side of the family with histologically or death certificate proven prostate cancer where at least one is diagnosed at <70 years
- Men with three relatives on the same side of the family with histologically or death certificate proven prostate cancer diagnosed at any age
Or (2) Men of African or Afro-Caribbean ancestry defined as:
- Both parents and all 4 grandparents from that origin
Or (3) Men of any ethnicity who have been found to have inherited a gene mutation that increases risk of prostate cancer (e.g. BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol).
- Age 40- 69 years
- WHO performance status 0-2
- Previous cancer with a life expectancy of less than five years.
- Previous prostate cancer
- Negative biopsy within one year before recruitment
- Comorbidities making prostate biopsy risk unacceptable (anticoagulants or antiplatelet medication including Warfarin, Clopidogrel, Apixaban, Dabigatran or other NOAC (Novel Oral Anti-Coagulant); poorly controlled diabetes, cardiovascular/respiratory disease, immunosuppressive medication or splenectomy).
- Men with body mass index (BMI) 40 and above.
- Men with BMI 35 and above plus other co-morbidities.
- Contraindications to having an MRI (pacemakers, aneurysm clips, metallic cardiac valve/stent, Ventriculo-Peritoneal (VP) shunt, cochlear implant, neurotransmitter, metallic foreign bodies in eye(s), other metalwork, claustrophobia)
- Any significant psychological conditions that may be worsened or exacerbated by participation in the study
A pilot of 100 men were recruited at The Royal Marsden NHS Foundation Trust aiming to inform the feasibility and accessibility of the study approach. The full study is an extension of the PROFILE pilot study, aiming to recruit (i) 350 men of European ancestry with a family history of prostate cancer; (ii) 350 men of black African or Afro-Caribbean descent; and (iii) 350 men of any ethnicity who have been found to have inherited a gene mutation that increases risk of prostate cancer (i.e. high-risk gene mutation).