Andrew Siegel MD 2/28/15
The Dilemma
The downside of screening is over-detection of low-risk prostate cancer that may never prove to be problematic, but may result in unnecessary treatment with adverse consequences. The downside of not screening is the under-detection of aggressive prostate cancer, with adverse consequences from necessary treatment not being given.
The Buck Stops Here
Prostate biopsy (ultrasound guided) is the definitive and conclusive test for prostate cancer. An elevated PSA (Prostate Specific Antigen) blood test or an abnormal DRE (digital rectal exam) are the findings that typically lead to the recommendation for prostate biopsy.
What’s New In Prostate Cancer Screening?
The following are refinements in the screening process that can help make the decision about whether or not to proceed with a prostate biopsy, potentially sparing some from the need to undergo the biopsy and clearly indicating the need for biopsy in others.
- Free PSA
- PSA Velocity
- PSA Density
- PCA-3
- Prostate MRI
- 4K Score
Free PSA
PSA circulates in the blood in a “free” form, which it is unbound and a “complex” form, in which it is bound to a protein. The free/total PSA can enhance the specificity of PSA testing. The greater the free/total PSA, the greater the chances that benign enlargement of the prostate is the cause of the PSA elevation. In men with a PSA between 4-10, the probability of cancer is less than 10% if the ratio is greater than 25% whereas the probability of cancer is almost 60% if the ratio is less than 10%.
PSA Velocity
It is extremely useful to compare the PSA values from year to year. Under normal circumstances, PSA increases by only a small increment, reflecting age-related benign prostate growth. PSA acceleration at a rate greater than anticipated is a red flag that may be indicative of prostate cancer and is one of the most common prompts for undergoing biopsy.
PSA Density
There is a direct relationship between prostate size and PSA, with larger prostates producing higher PSA levels. PSA density (PSA/prostate volume) is the relationship of the PSA level to the size of the prostate. PSA density > 0.15 is a red flag that may be indicative of prostate cancer.
PCA-3 (Prostate Cancer Antigen-3)
PCA-3 is a specific type of RNA (Ribonucleic Acid) that is released in high levels by prostate cancer cells. Its expression is 60-100x greater in prostate cancer cells than benign prostate cells, which makes this test much more specific for prostate cancer than PSA. PCA-3 is a urine test. The prostate is gently “massaged” via DRE to “milk” prostate fluid into the urethra. The first ounce of urine voided immediately after massage is rich in prostatic fluid and cells and is collected and tested for the quantity of PCA-3 genetic material present. Urinary levels of PCA-3 are not affected by prostate enlargement or inflammation, as opposed to PSA levels. PCA-3 > 25 is suspicious for prostate cancer.
Prostate MRI (Magnetic Resonance Imaging)
MRI is a high-resolution imaging test that does not require the use of radiation and is capable of showing the prostate and surrounding tissues in multiple planes of view, identifying suspicious areas. MRI uses a powerful Tesla magnet and sophisticated software that performs image-analysis, assisting radiologists in interpreting and scoring MRI results. A validated scoring system known as PI-RADS (Prostate Imaging Reporting and Data System) is used. This scoring system helps urologists make decisions about whether to biopsy the prostate and if so, how to optimize the biopsy.
| PI-RADS classification | Definition |
| I | Most probably benign |
| II | Probably benign |
| III | Indeterminate |
| IV | Probable cancer |
| V | Most probably cancer |
4Kscore Test
The 4Kscore Test measures the blood content of four different prostate-derived proteins: Total PSA, Free PSA, Intact PSA and Human Kallikrein 2. Levels of these biomarkers are combined with a patient’s age, DRE status (abnormal DRE vs. normal DRE), and history of prior biopsy status (prior prostate biopsy vs. no prior prostate biopsy). These factors are processed using an algorithm to calculate the risk of finding a Gleason score 7 or higher (aggressive) prostate cancer if a prostate biopsy were to be performed. The test can increase the accuracy of prostate cancer diagnosis, particularly in its most aggressive forms.
(It cannot be used if a patient has received a DRE in the previous 4 days, nor can it be used if one has been on Avodart or Proscar within the previous six months. Additionally, it cannot be used in patients that have within the previous six months undergone any procedure to treat symptomatic prostate enlargement or any invasive urologic procedure that may be associated with a PSA elevation.)
As of now, the test is not covered by insurance and costs $395 from the lab that performs it.
Bottom Line: Excluding skin cancer, prostate cancer is the most common cancer in men (accounting for 26% of newly diagnosed cancers with men having a 1 in 7 lifetime risk). The median age of prostate cancer at diagnosis is the mid 60’s and there are 221,000 new cases per year, 27,500 deaths (the second most common form of cancer death, after lung cancer) and there are currently about 2.5 million prostate cancer survivors in the USA. It is important to diagnose prostate cancer as early as possible in order to decide on the most appropriate form of management–surgery, radiation, or observation/monitoring (the most common treatment pathways, although there are other options as well). These refinements in the screening process can help urologists make the decision about whether or not to proceed with a prostate biopsy.
Wishing you the best in health,
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