PSA Screening

Prostate cancer screening in the general population is based mainly on the measurement of prostate specific antigen (PSA) levels in the blood, but there is considerable uncertainty surrounding the PSA threshold at which men should be referred for prostate biopsy.

Blood PSA levels can vary depending on age and race, and also with non-cancerous conditions such as prostatic inflammation and benign prostate hyperplasia (BPH). Some studies also suggest that PSA levels can be proportionately higher in first-degree relatives of men with prostate cancer, although this is inconclusive. As a result, there is debate whether PSA thresholds for biopsy should vary with age, both in general, and high-risk populations.

At present, one commonly accepted threshold for biopsy is 4.0ng/ml, but recent evidence suggests that a proportion of prostate cancers will be missed when the threshold is set at this level. Please refer to the IMPACT Study Protocol for a review of the evidence surrounding PSA threshold.

One of the main aims of the IMPACT study is to determine the sensitivity and specificity of PSA screening for prostate cancer in male BRCA1 and BRCA2 carriers, and controls. In other words, within this population IMPACT aims to assess what proportion of men who have an elevated PSA level do actually harbour prostate cancer, and what proportion of men do not. It also aims to determine age-specific PSA levels in BRCA1 and BRCA2 mutation carriers.

Two large general population-based screening studies, the ERSPC (European Randomized study of Screening for Prostate Cancer) study and the British ProtecT (Prostate testing for cancer and Treatment) study, are currently being conducted in Europe and the UK. These studies are using 3.0ng/ml as the PSA threshold for biopsy. IMPACT will use the same threshold for biopsy. Participants will undergo annual PSA testing over a minimum of five years.

A second aim of the IMPACT study is to evaluate the sensitivity and specificity of new serum and urine markers of prostate cancer in BRCA1 and BRCA2 mutation carriers. Efforts to improve the specificity of serum PSA using different diagnostic parameters have been discussed widely in the academic literature and potential new prostate cancer markers include age-adjusted PSA, free to total PSA fraction, PSA density and PSA velocity. It is hoped that markers will be identified which can distinguish between latent and aggressive forms of the disease.

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