The PROFILE Study: Understanding why some people are at higher risk of prostate cancer

The PROFILE study aims to understand why some individuals with prostates, including those of Black African/Black-Caribbean ancestry, are at greater risk of prostate cancer. Understanding the genetics that influence risk of prostate cancer could improve the way we screen for prostate cancer in the future, and help more people get diagnosed and treated early.

Winston, Richard, Frederick and Olivier talk about why it is important to understand prostate cancer risk and what it is like to take part in the PROFILE study. This video was created in partnership with the patients/members of the public and the PROFILE team in an involvement project led by Dr Emma Hainsworth, Nurse Researcher at The Royal Marsden. It was funded by a patient and public involvement and engagement grant from the NIHR Biomedical Research Centre at The Royal Marsden Hospital and The Institute of Cancer Research.

Taking part

The PROFILE study is currently recruiting people aged 40-69 years who are at greater risk of prostate cancer, including men of Black African or Black African-Caribbean ancestry, men with genetic mutations known to increase their risk, men with a positive family history of prostate cancer and transgender women with any of these factors. 
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

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 52,000 new cases diagnosed each year and a lifetime risk of 1 in 8 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 people from certain ethnic groups also have a higher risk of prostate cancer, and this includes men of Black African or Black African-Caribbean ancestry. This study aims to look at people 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 any ethnicity with a family history of prostate cancer (defined as having at least one first degree (or second degree if through the female line) relative with prostate cancer diagnosed at <70 years); (ii) men of Black African or Black African-Caribbean ancestry (defined as having both parents and all four grandparents of either Black African or Black African-Caribbean ancestry and (iii) men of any ethnicity with a known genetic predisposition to having prostate cancer e.g., being known to carry a mutation in a high-risk gene; and/or being known to be in the top tenth percentile of the polygenic risk score (high PRS score) prior to enrolment, (iv) transgender women with any of these factors, 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 people 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 those with high prostate cancer risk.

The aim of the PROFILE study is to investigate the role of targeted prostate cancer screening in people 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:

1. Men of any ethnicity with a family history of prostate cancer.
2. Men of Black African or Black African-Caribbean ancestry.
3. Men of any ethnicity with a genetic predisposition to having prostate cancer e.g., having a pathogenic mutation in a gene thought to cause a higher-risk of prostate cancer: (including BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations) and/or known to have a high PRS score (defined as being in the top 10^th centile prior to enrolment).
4. Transgender women with any of these factors.

Those 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 people 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 and the PSA test may be an unreliable indicator for cancer in transgender women receiving gender affirming hormonal therapy. 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 participants may opt not to have biopsy at baseline (i.e., initial stage). These people 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 individual 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

Either:

(1) People registered male at birth of any ethnicity (with the exception of Black African/Black African-Caribbean who fit into cohort 2) with a positive family history of prostate cancer defined as:

• a first degree relative (or second degree if through female line) with histologically or death certificate proven prostate cancer diagnosed at <70 years.
• 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.
• three relatives on the same side of the family with histologically or death certificate proven prostate cancer diagnosed at any age.

Or (2) People registered male at birth of Black African or Black African-Caribbean ancestry defined as:

• Both parents and all 4 grandparents being of either Black African or Black African-Caribbean.

Or (3) People registered male at birth of any ethnicity with a genetic predisposition to having prostate cancer e.g., having 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) and/or known to have a high PRS score (defined as being in the top 10^th centile prior to enrolment).

• Age 40- 69 years.
• WHO performance status 0-2.

Exclusion criteria

• 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).
• People with body mass index (BMI) 40 and above.
• People with BMI 35 and above plus other co-morbidities.
• Contraindications to having an MRI (non-MRI compliant 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 participants of any ancestry with a family history of prostate cancer; (ii) 350 participants of Black African or Black African-Caribbean ancestry; and (iii) 350 participants of any ethnicity with a high genetic risk to having prostate cancer (e.g., having inherited a gene mutation that increases risk of prostate cancer (i.e. high-risk gene mutation) and/or known to have a high PRS score).