Age-Adjusted PSA Levels, PSA Density and PSA Velocity

Age-adjusted PSA levels set a different upper limit of normal for each decade: below 2.5 ng/mL for men aged 40 to 49, 3.5 for 50 to 59, 4.5 for 60 to 69 and 6.5 for 70 to 79. Dr. Nitin Shrivastava treats a PSA as abnormal only when at least two readings exceed the limit for the man's age, and uses PSA density and velocity to resolve borderline results.

PSA, or prostate-specific antigen, is a protein made by the prostate gland and measured in a routine blood test. It is the most widely used test in the early detection of prostate cancer, and also one of the most frequently misread. Dr. Nitin Shrivastava, a urologist and uro-oncologist, describes it as a very important and basic blood test that has been in use for many years, but one that rises in several conditions besides cancer. This article sets out how he interprets it: the age-adjusted thresholds, the two-reading rule, the supporting measures of density and velocity, the testing schedule for high-risk men and the situations in which a raised PSA means little. The wider diagnostic pathway is described in the complete guide to prostate cancer early detection.

Why a raised PSA is not a diagnosis

A high PSA tells the clinician that something is happening in the prostate, not that the cause is cancer. Dr. Shrivastava lists three common reasons for a high reading:

• retention of urine, when the bladder cannot empty;
• infection of the urinary tract or prostate;
• cancer.

In all three situations PSA readings are high. That is why he insists that the clinician be clear the patient needs the test, and discuss it with him, before ordering it. Asked which other hormones or markers should be monitored in prostate cancer, his answer was short: none. PSA is the marker.

Normal PSA levels by age: age-adjusted reference levels

PSA rises naturally with age, largely because the prostate enlarges, so a single cut-off for all men is misleading. A value that is unremarkable in a man in his seventies can be a warning sign in a man in his forties. Dr. Shrivastava uses the following age-adjusted reference levels, below which PSA is considered within range:

These values match the age-specific reference ranges widely used in urology. When doctors asked him during the discussion what PSA cut-off should prompt a prostate biopsy, and which PSA values should be regarded as dangerous, he returned to this table each time.

The two-reading rule

A single PSA result should never decide the next step. Dr. Shrivastava does not proceed on one reading: he requires at least two PSA results above the age-adjusted level before he regards the PSA as abnormal. In his summary, a single PSA does not mean anything.

If a PSA comes back abnormal, he repeats it after four to six weeks. A rise confirmed on two occasions, particularly in a man with a family history of prostate cancer, is an indication for biopsy.

PSA density and PSA velocity

When the PSA is borderline, PSA density and PSA velocity add the clues that the raw number cannot. Dr. Shrivastava uses both to decide whether a borderline result is suspicious enough to justify a biopsy.

PSA density

PSA density is the PSA value divided by the volume of the prostate, usually measured in millilitres on ultrasound or MRI. It corrects for the fact that a large benign gland produces more PSA than a small one. The same PSA value carries less weight in a very large prostate than in a small one.

Dr. Shrivastava's threshold is clear: a PSA density above 0.15 is suspicious for cancer. He also includes a PSA density above 0.15 among the features that place a man in the high-risk group.

PSA velocity

PSA velocity is the rate at which PSA rises over time, calculated from serial measurements. A cancer tends to push PSA up faster than benign enlargement does. Dr. Shrivastava's threshold: a PSA rising by more than 0.75 ng/mL per year is suspicious.

Velocity is particularly useful in younger men. Asked what factors, other than urinary infection, should be considered when interpreting age-adjusted PSA levels, he answered that very few things other than infection produce a very high PSA. In a young patient especially, the factors to weigh are the rise across subsequent PSA tests, the PSA velocity and the PSA density.

Who should have PSA testing, and how often

PSA testing should be targeted at men with symptoms and men at higher risk, not offered to every man as a mass screening test. Dr. Shrivastava does not recommend routine mass screening (the reasoning is set out in the complete guide). For high-risk men, by contrast, he advises investigation from an earlier age than usual.

Who is in the high-risk group

He asks clinicians to focus on a handful of practical criteria rather than on genetic testing:

• men of African descent;
• men with a family history of prostate cancer or of multiple cancers;
• men with a PSA density above 0.15.

Men with these features should be investigated from the age of 45. Men of African descent are recognised internationally as having a higher incidence of prostate cancer and a higher risk of dying from it, which is why many guidelines advise starting the conversation about testing earlier for them.

PSA testing schedule for African patients

For African patients, Dr. Shrivastava's schedule is:

1. A baseline PSA for every man above 40. This sets the reference point against which later readings are judged.
2. Yearly PSA testing from the age of 45. For a high-risk man with a normal PSA, a yearly check is the right interval.
3. Repeat any abnormal result after four to six weeks. A single high value is not acted on.
4. Refer for biopsy if the PSA rises on two occasions. A rise in subsequent PSA levels is itself suspicious, especially in a man with a family history.

Even a man with no urinary symptoms, if he is high risk because of a family history of prostate cancer, can be offered this discussion and PSA testing.

When a high PSA is misleading

Two situations account for many falsely alarming PSA results: urinary infection and urinary catheters.

Urinary infection

Infection is the main cause of a high PSA that must be excluded before any further step. If a patient with a high PSA is running a fever, has burning on passing urine and his urine examination shows infection, Dr. Shrivastava advises treating the infection with antibiotics, waiting a few weeks and then repeating the PSA. Acting on the first reading in this setting risks an unnecessary biopsy.

PSA in men with a urinary catheter

PSA rises after catheterisation, and there is no cut-off value for a catheterised patient. Asked what PSA level should be considered raised in a catheterised man over 60, Dr. Shrivastava explained that a slight increase is expected in any patient on a catheter, and that readings of around 8 to 10, or sometimes close to 20, can be seen.

In these men he relies on clinical judgement and the rectal examination rather than on a number. If the PSA keeps rising, he advises an MRI of the prostate to establish what is happening inside the gland. He described this as a very difficult clinical situation, which is why the decision rests on the trend and the examination together. The full exchange is recorded in the Live Discussion from this masterclass.

Putting PSA interpretation into practice

The value of Dr. Shrivastava's approach lies in its discipline. Each step removes a common source of error:

• Ordering with intent prevents testing that the patient has not agreed to and does not need.
• Age-adjusted levels stop older men with benign enlargement being labelled abnormal.
• The two-reading rule and the four-to-six-week repeat filter out transient rises.
• Excluding infection removes the most common false alarm.
• Density and velocity sharpen the decision in the borderline zone.

Only after these filters does a raised PSA justify a biopsy. How Dr. Shrivastava makes that decision, and how the biopsy is done, is covered in the article on when to do a prostate biopsy. For a complementary perspective on PSA, including the free-to-total PSA ratio and PSMA PET CT, see the PSA test guide by Dr. Shafiq Ahmad.