prostate specific antigen (PSA)

see also:

• prostate cancer
• benign prostatic hyperplasia (BPH)
• NNT.com - PSA screening does NOT decrease deaths from prostate cancer but increases risk of biopsies and prostatectomy with their potentially relatively high morbidities

• PSA is a serine protease produced by prostatic epithelium and secreted into semen
• its normal function is to cleave and liquefy the seminal coagulum formed after ejaculation.
• in normal men, only minute amounts of PSA circulate in the serum.
• free PSA is inactive as the molecules were either immature (pro-PSA) or inactivated (nicked PSA) and has a half-life of only 2-3hrs
• bound PSA is active PSA which has escaped the prostate gland and rapidly bound to anti-protease proteins, bound PSA has a half-life of 2-3 days.
• levels of free PSA and bound PSA rise in conditions causing intermittent showers of PSA to enter the blood
• chronic prostate conditions such as cancer generally are associated with raised bound PSA rather than free PSA
  • 80% of patients with a free PSA level < 8% will have prostate cancer as the cause of their raised bound PSA.
  • BEWARE though, delays in measuring the assay of > 24hrs of collection will result in a false low level of free PSA due to short half life in vitro.
• note that sensitivity for cancer using the upper limit for age is still only 60%.
• use of 5ARI medications such as finasteride decrease PSA results by ~50% which thus affects interpretation of results
• elevated levels of PSA occur in:
  • benign prostatic hyperplasia (BPH)
    • PSA levels rise with prostate size hence the use of age-specific upper level ranges for PSA:
      • 40-49yrs = 2.5 ng/ml
      • 50-59yrs = 3.5 ng/ml
      • 60-69yrs = 4.5 ng/ml
      • 70-79yrs = 6.5 ng/ml
    • free PSA / total PSA > 25% is suggestive of BPH rather than cancer
    • PSA may double every 5 years in the early stages of BPH, but if rate of rise is faster than this then cancer is suggestive
  • prostate cancer
    • PSA > 10 ng/ml is strongly indicative of cancer in men without prostatism under the age of 75yrs
    • rate of rise of PSA over 3 measurements > 0.75ng/ml/year is suggestive of cancer
    • BUT 20-40% of men with organ-confined prostate cancer will have PSA < 4.0 ng/ml (ie. “normal” for older men)
    • free PSA / total PSA < 10% is suggestive of cancer
  • prostatitis
    • sub-clinical prostatis may be common in BPH and cause episodes of raised PSA
    • clinical prostatitis is usually associated with PSA > 20 ng/ml so PSA for cancer risk should be measured at least 1 month after its full resolution
  • instrumentation of the prostate
  • following ejaculation
• serial measurements of PSA is very useful in monitoring response to Rx of prostate cancer

• PSA testing was introduced in the 1980's and its introduction has been associated with a 25% reduction in mortality from prostate cancer, and much earlier diagnosis with 80% of diagnoses now being made with localised disease, with most men being diagnosed 9 years prior to metastatic disease, and the previously relatively common presentation of acute paraplegia due to prostate cancer metastatic lumbar spine cord compression now quite rare.
• nevertheless screening with PSA has also been problematic with high rates of false positive for prostate cancer and the associated anxieties and potentially unnecessary medical interventions which this entails.
• after the onset of benign prostatic hyperplasia (BPH) in the late 40yrs, rising psa levels with BPH reduces the sensitivity of PSA testing for prostate cancer, although levels of PSA > 10ng/ml is still very indicative of the presence of prostate cancer.
• PRIOR to onset of BPH (eg. around 45 years of age), a PSA level of between 2-3 ng/ml gives a 19-fold risk for development of prostate cancer in later life, while a level of about 0.6 ng/ml had a very low risk of developing prostate cancer.¹⁾

• this assumes no recent clinical prostatitis or instrumentation within past month

• lower than normal risk for cancer
• repeat in 3-5 years as cancer risk is < 1%
• if age > 70yrs, unlikely to benefit from further testing

• above average risk for cancer but not sufficient risk to justify the risks of biopsy.
• these patients should have annual PSA and digital rectal examination.
• this testing should be more frequent (3-6 months) in those who have a higher pre-test probability for cancer such as FH in a close relative, especially a brother. In these patients a free-bound ratio should also be done.

• repeat PSA in 2 weeks as it may have been due to subclinical prostatitis in BPH.
• If the level falls, it is unlikely to be cancer.
• If it doesn't fall, then a free-bound PSA ratio should be done.
  • 80% of patients with a free PSA level < 8% will have prostate cancer as the cause of their raised bound PSA.

• refer to a urologist as risk of cancer being present is ~80% if no clinical prostatism and age < 75yrs

• sensitivity appears to be ~70% which is twice as good as PSA
• more importantly, false positive rate of only 4% which is about 10x better than the PSA
• see http://www.dailymail.co.uk/health/article-1361832/prostate-cancers-reliable-test-Urine-screening-detects-50-cases.html