What is Prostate Specific Antigen (PSA)?
It is a glycoprotein expressed by prostate cancer cells, both normal and neoplastic. Though the normal prostate produces more PSA but levels are elevated more in prostate cancer because there is more release of the same in body circulation due to disruption of basement membrane. It is a tumor marker used for screening of prostate cancer and to assess the extent of prostate cancer and volume of the disease. It is also used to assess the response to treatment.
How much elevation of PSA is considered to be significant?
The value for normal range of PSA is highly controversial. Previously, levels above 4 ng/ml were considered to be abnormal but fixing this as the upper limit doesn’t seem to be correct as the levels of PSA increase with age in an individual, due to the increasing size of prostate gland.
Different normal reference ranges have been identified based on several studies-
- 40 to 49 years – 0 to 2.5 ng/mL
- 50 to 59 years – 0 to 3.5 ng/mL
- 60 to 69 years – 0 to 4.5 ng/mL
- 70 to 79 years – 0 to 6.5 ng/mL
What conditions may cause the PSA elevation other than prostate cancer?
Other than prostate cancer, there are some benign conditions that may cause PSA elevation.
- Lower tract endoscope manipulation
- Transrectal & transperineal prostate Bx
- Acute urinary retention
- Digital rectal examination
- Prostate massage
- Acute prostatitis
So if you get your PSA checked and find the level higher than normal, it is not always a thing to be worried as one of the above causes can be the cause for the same.
But the question is how much levels can be considered safe?
Level of more than 4 ng/ml is seen in around 70% of the cases of prostate cancer. Levels of PSA between 4 to 10 ng/ml could be overlapping for benign and malignant causes. In such cases, PSA velocity and Percent-Free PSA may be helpful to differentiate between the two.
It is the change in PSA values over time. PSA levels that continue to rise over time are more in favour of prostate cancer as compared to ones that are stable. It increases the specificity of a single PSA measurement for early cancer detection. Normal levels are around 0.75ng/ml/year. Current recommendation include collection of PSA velocity over not less than 18 months and the use of three values to calculate PSA velocity.
Percent Free PSA
It is free PSA, expressed as a ratio with total PSA. It has been approved for early detection in patients with PSA between 4 & 10 ng/ml. In he PSA range of 4 to 10 ng/ml, the lower value of percentage free PSA goes in favor of prostate cancer compared to benign causes.
What if the PSA levels are in favor of prostate cancer?
In case the level of PSA is significantly high, or in favour of malignancy if not very high (as discussed above), further testing has to be done to confirm or rule out the diagnosis of prostate cancer. Digital rectal examination, MRI pelvis and/or prostate biopsy needs to be done to confirm the diagnosis.
Is PSA elevated in all the cases of prostate cancer?
Usually basement membrane breach causes PSA elevation in most of the cases of prostate cancer. But some very early disease may no cause it to be significantly elevated. Also, most cases of prostate cancer are adenocarcinoma, but in a less common variant called small cell carcinoma, the PSA elevation may be too less as compared to the disease bulk and stage. So the PSA elevation may not always correlate with the disease volume and spread in such cases.
What are the clinical applications of PSA?
Along with other investigations, it is a part of screening workup for prostate cancer in high risk individuals. Different studies have suggested different cutoffs for the PSA levels that are considered to be above the normal range to be considered for further diagnostic tests.
Monitoring treatment response
It helps in monitoring the response to treatment in prostate cancer. If it is well controlled on a particular therapy, it is an indicator of response to treatment. And if it increases while on treatment, it may indicate loss of response to the same, which then has to be correlated with imaging to see the disease extent and compare with the previous imaging findings.
Detection of early recurrence
If a patient has been treated previously, and is on follow up with regular monitoring of PSA, if the levels start rising thereafter, it may be an indicator of disease relapse or recurrence, and he needs to undergo further testing to confirm the same.