Feature Articles » Prostate Cancer (Improving PSA as a screening Test)

by Dr Tay Miah Hiang

Prostate cancer is a disease that is climbing up the charts in Singapore. A decade ago, prostate cancer was ranked as 5th most prevalent cancer amongst men but the most recent epidemiological study suggests it is now 3rd most prevalent, behind colon and lung cancer.

The reasons for this phenomenon are the aging population and dietary indiscretion as we veer to more animal protein than soy and vegetable based as well as increase in incidental prostate cancer that are picked up during health screens.

The use of PSA as a screening test may be able to pick up prostate cancer at the earliest stage but there are several considerations before jumping to conclusion.

While a highly elevated PSA level is pathognomonic of prostate cancer, the differential of a mildly or moderately elevated PSA may be caused by benign prostate hyperplasia, prostatis, recent urethral irritation or even ejaculation within the last 24-48 hours.

Conversely, a normal level may not necessary indicate that cancer does not exist. In fact, drugs such as finasteride or dutersteride and even ketoconazole may falsely lower the measured PSA level and the real level may in fact be higher and therefore warrant further investigation.

By convention, we will take the real PSA level as 2 times the measured level if the patient is taking such medication. Therefore, it is important to take a very detailed medical history.

Sensitivity and specificity of PSA are also dependent on age. The older the person, the less likely a particular level of PSA is related to prostate cancer than a younger person. Therefore, although we do not recommend their use, age-specific reference ranges have been developed from normal populations to improve the discriminating power of PSA.

See Table 1.

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

Raising the PSA biopsy threshold in older men improves specificity, reducing the number of unnecessary biopsies. Conversely, lowering the threshold in younger men improves sensitivity and increases detection of early-stage tumors. The other laboratory test that may help to increase predicitivity of PSA test is the ratio of free PSA to complex PSA.

It is known that PSA in prostate cancer usually complexes to macromolecules in the serum rather than in the free form. Therefore, the ratio of free-to-total PSA is reduced in men with prostate cancer. Hence, biopsies should be performed only in men with lower ratios.

For example, men 50 to 75 years of age with PSA levels between 4.0 and 10.0 ng/mL, including the cancer detection rate for this PSA range in screening populations is about 25 %. However, the detection rate increased to 56 % for men with a free-to-total PSA ratio less than 10 percent.

Hence, while we can subject all patients with moderately high PSA and normal prostate gland examination on digital rectal examination to a prostate biopsy to ascertain the diagnosis, we can also potentially reduce unnecessary prostate biopsy in men with a much lower risk of prostate cancer such as one with a PSA level between 4 and 10 ng/ml, normal prostate gland on DRE and a high free PSA to total PSA.

A decade ago, prostate cancer was ranked as the fifth most prevalent cancer amongst men but the most recent epidemiological study suggests it is now the third most prevalent, behind colon and lung cancer.

There are also other ways to improve the PSA predicitibility such as (1) PSA velocity over time which require a much longer time to assess or the use of more sophisticated test respectively. Study has shown that a PSA rate of change greater than 0.75 ng/mL/year is at increased risk of being diagnosed with prostate cancer and that PSA velocity was more specific than a 4.0 ng/mL PSA cutoff (90 versus 60 percent specificity).

This is, however, based on a study with small sampling size and there are significant short-term physiologic variations in the PSA level Accurately measuring PSA velocity requires three serial readings, ideally with the same assay, obtained over at least a 12- to 24-month period; (2) PSA density measurement is based upon the observation that prostate cancers can produce approximately 10 times more PSA per volume of prostate tissue than benign conditions PSA density measurements, which adjust PSA values for prostate volume, have reported to better discriminate between cancer and noncancer groups than PSA levels alone.

However, the impracticality of needing transrectal ultrasound or MRI to measure the prostate volume and the lack of consensus over the cut-off level makes this option less viable.

In summary, there is a trend of increased diagnosis of prostate cancer and may allude to many reasons. Measuring PSA may have more impact than one perceives. We have to interpret the value specifically for that person and make decision to continue surveillance if the risk of prostate cancer is low or immediately subject him to prostate biopsy which, although has a low risk of complication, is nevertheless invasive and has its risk.