All about PSA (not Pharmaceutical Society of Australia)

What is PSA?

Prostate Specific Antigen (PSA) is a glycoprotein actually not there to help screen for prostate pathology but to act physiologically in the ejaculate to liquefy the semen allowing sperm to break free from their seminal coagulum prison and swim freely; is likely to be instrumental in dissolving the cervical mucous via its proteolytic qualities, allowing the entry of sperm. PSA leaks into serum normally, and is present in the circulation of healthy men. Various prostate pathology will increase PSA eg. Prostatitis, BPH, Prostate CA etc. So PSA serum levels are used as a screening test.

What are some of the factors that can affect PSA levels?

PSA has not diurnal variation. Normal healthy males’ PSA levels don’t change. Ejaculation increases PSA levels, but they return to normal within 24 hours Some say riding pushbikes and motorbikes increases PSA too, but evidence remains inconclusive. Some drugs like cyclophosphamide and others can increase PSA too. DRE gives no significant change in PSA. BUT a vigorous prostate massage can produce a short-term 2-fold increase….Nothing sus. Cystoscopy, urethral catheterization, and TRUS do not tend to elevate the PSA level. Prostate needle biopsy increases PSA by a median of 7.9 ng/mL (6.5 times baseline value) within 5 minutes following the biopsy, this persists for 24 hours. Urinary retention increases PSA levels, but when relieved, they decrease 50% in hours. Acute prostatitis produces large increases in PSA, but the return to baseline depends on resolution of the infection, which may take 6-8 weeks or longer. PSA levels have been used to determine the duration of antimicrobial therapy in men with acute bacterial prostatitis. PSA half-life is days. After a biopsy, 2 to 4 weeks may need to elapse before the PSA returns to its original level.

What investigations would be most helpful and why?

DRE of course - Although PSA testing detects more cancers than DRE, a combination of the 2 methods is better: DRE detects more cancers at the PSA cutoff of 4.0 ng/mL, but this may not occur if the cutoff is lowered to 3.0 ng/mL. In men with prostate cancer whose PSA level was less than 4 ng/mL, normal DRE findings were present in 4-9%, while DRE findings were positive in %. When the PSA level was greater than 4 ng/mL, negative DRE results were found in 12-32% of patients, while positive DRE results were present in 42-72% of patients. TRUS Biopsy Cancer markers in general… Alkaline phosphatase Other Prostate cancer markers… Human glandular kallikrein–2 Prostate-specific membrane antigen Cell cycle inhibitor p27 Serum insulinlike growth factor

Few issues in medicine are as controversial as screening for prostate cancer. Briefly discuss why this is the case.

PSA testing it has a Positive predictive value of about 35% when the cutoff is about 3ng/mL (but we normally have cutoff at 4ng/mL PSA testing with a cutoff of 4 ng/mL has a sensitivity of %  implies that 20-30% of cancers are missed when only the PSA level is obtained. The sensitivity can be improved by lowering the cutoff or by monitoring PSA values so that a rise in PSA level of more than 20-25% per year or an increase of 0.75 ng/mL in a year would trigger performance of a biopsy regardless of the PSA value. The specificity of PSA at levels greater than 4 ng/mL is 60-70%. Specificity can be improved by using age-adjusted values, Men with low readings might still harbor dangerous cancers (gleason stage 5 might not produce PSA anymore), while those with high readings might be completely healthy. PSA, while normally at a steady serum concentration, can be affected by a lot of things (see above) Studies have shown that screening does not reduce the death rate in men 55 and over. NNT = 48 That’s 47 men who, in all likelihood, can no longer function sexually or stay out of the bathroom for long because the PSA test was justification for a urologist to jab it. More suited to monitor remission of prostate cancer etc

If screening is to be carried out which patients might be targeted and why?

Don’t screen for prostate cancer in men aged 75 years or older – they will die WITH CA rather than FROM it Screening when male and: 40yrs + family Hx of prostate CA or proven BRCA1/2 etc 50yrs + No family Hx recent onset of LUTS