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The PROFILE Study: Germline genetic profiling: correlation with targeted prostate cancer screening and treatment

The aim of the PROFILE study is to investigate the role of targeted prostate cancer screening in men with a family history of the disease and with the role of specific genetic profiles and biomarkers. This study has been designed using an observational approach to look at the correlation of cancer incidence (on biopsy) with genetic profile.

The aim is to evaluate targeted screening for prostate cancer in men with a family history of the disease and those of Afro Caribbean descent, to estimate the incidence of prostate cancer, the sensitivity and specificity of Prostate Specific Antigen (PSA) screening in these populations and correlate this with single nucleotide polymorphism (SNP) profiles and biological endpoints.

Two cohorts will be recruited:

  1. Men with family history of prostate cancer.
  2. Men of Afro Caribbean descent.

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 12 core biopsy will be done with a SNP profile and Diffusion Weighted Magnetic Resonance Imaging (DWMRI).  If benign the patient will be followed with 6 monthly PSA readings for 5 years and re-biopsied if PSA rises > 50%.

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 has been 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. These men will be followed up six monthly PSA and biopsy performed 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

Men with either:

1) A positive family history of PrCa defined as:

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

 2) Of African or Caribbean ancestry defined as:

  • Both parents and all 4 grandparents from that origin

3) Age 40-69 years.

4) World Health Organisation (WHO) performance status 2.

5) Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow up schedule.

Exclusion criteria

  • Non-Caucasian ethnicity (including Mixed race or Jewish).
  • Previous cancer with a life expectancy of less than five years.
  • Previous diagnosis of prostate cancer.
  • Negative biopsy within one year before recruitment.
  • Comorbidities making prostate biopsy risk unacceptable (Warfarin or Clopidogrel).
  • Contraindications to having an MRI (pacemakers, aneurysm clips, claustrophobia).

A feasibility pilot recruitment of 100 men from the target population evaluated positively at The Royal Marsden NHS Foundation Trust in London.

This pilot is now being extended with recruitment proposed of 350 Caucasian men with a family history of PrCa and 350 men of Afro-Caribbean descent.