The role of PSA-based screening for prostate cancer is still under debate. But many men are advised by their general practitioner to have their PSA levels checked regularly. This is the easiest way to identify those men that have an increased risk of having prostate cancer. It also may help to detect prostate cancer at an early and curable stage. But when your doctor then tells you that you have an elevated PSA, a lot of questions come to mind: Do I really have prostate cancer? What to do next? Do I really need a prostate biopsy to know if I have prostate cancer? Are there other ways to rule out the presence of prostate cancer that are quick, reliable, and avoid the side effects of an invasive biopsy?
What is a PSA test? What do the results mean?
A PSA test is a simple blood test that measures the amount of prostate-specific antigen (PSA). Your blood naturally contains small amounts of this protein that is produced in the prostate.
As you get older and your prostate gets bigger, the amount of PSA in your blood rises. An increased PSA level is a first indication that you have a problem with your prostate. This does not necessarily mean that you have prostate cancer. An inflamed prostate (prostatitis, for instance due to a previous urinary infection) or an enlarged prostate (benign prostate hyperplasia (BPH), adenoma) can also cause PSA levels to rise. So, a PSA test cannot discriminate between ‘benign’ prostate conditions and prostate cancer.
In addition to the low specificity for prostate cancer, the PSA test is not able to discriminate between a more aggressive prostate cancer from one that is less likely to cause harm. This is thought to lead to overtreatment.
If your PSA is elevated, your urologist will perform a digital rectal examination (DRE) to determine the size, shape, and surface of your prostate and look for signs of cancer. This will give your doctor more information whether you need to undergo either additional tests or a prostate biopsy.
What is a prostate biopsy? How does it work?
During a prostate biopsy, the doctor takes small pieces of tissue from different areas of the prostate using a thin needle. There are two types of prostate biopsy:
- TRUS-guided biopsy: guided by transrectal ultrasound, a needle is inserted into the prostate under local anaesthesia through the wall of the rectum. This is the most commonly used method.
- Transperineal (template or targeted) biopsy: guided by either MRI or a CT scan, a needle is inserted through the area of skin between the testicles and the rectum.
The tissue is observed under a microscope to see if any cancer cells are present. If the answer is yes, it is important to determine how aggressive the cancer is. This is indicated by a biopsy score (Gleason score) ranging from 6 to 10. The higher this score, the more aggressive the cancer is.
What is the difference between insignificant and aggressive prostate cancer?
It is important to know the type of cancer as this determines if treatment is necessary and which treatment is most suitable. The Gleason score indicates the type of cancer. Some prostate cancers are insignificant since they grow slowly (low Gleason score), while there are also prostate cancers that will grow aggressively (high Gleason score).
The first type may never cause any problems, even when left untreated and should in fact not be detected. The aggressive ones, as they grow fast, are more likely to spread outside of the prostate, and can become life-threatening. This type of prostate cancer should be diagnosed as soon as possible to ensure proper and timely treatment, which increases the chance of survival.
What information is provided by a prostate biopsy?
Currently, a prostate biopsy is the gold standard to diagnose prostate cancer since it allows to determine how aggressive the cancer might be. However, a prostate biopsy only shows the presence of cancer in the tissue pieces that were taken. There is a possibility of 25% that prostate cancer might be missed when 6 biopsy samples are taken . This means that a negative biopsy not necessarily guarantees that no cancer cells are present in your prostate.
Prostate biopsies not only find aggressive but also mild prostate cancer. This type of cancer may never cause any problems but is often treated (unnecessarily). Nonetheless, the diagnosis of an indolent prostate cancer may cause anxiety and a psychological burden to the patient.
Unfortunately, prostate biopsy is an invasive procedure: a biopsy has some risks. Side effects are different in type and severity for every man and one could:
- experience pain or discomfort during and after the biopsy
- see blood in the urine, sperm or stool
- get an infection (only small risk)
Sometimes these complications will require treatment and hospitalisation. Few cases of sepsis-related mortality following a prostate biopsy have been reported.
Are there other means for prostate cancer diagnosis?
In patients with increased PSA levels or a suspicious digital rectal examination (DRE), risk calculators based on clinical characteristics, imaging, and biomarkers might play a role in the diagnosis of prostate cancer. These can be used to determine your risk of having prostate cancer. If the result of either means is abnormal, you will still need a prostate biopsy to determine if you have prostate cancer.
Currently, multiparametric magnetic resonance imaging (mpMRI) is an increasingly used imaging technique for determining the risk of prostate cancer because of its non-invasive nature and the absence of ionising radiation. A mpMRI scan will give a detailed image of your prostate and makes it possible to see the difference between normal and suspicious tissue. The images also allow differentiation between aggressive and insignificant lesions. However, interpretation of these images is not straightforward and requires highly trained specialists in specialised centres. Waiting lists and travel time can be long for undergoing this procedure.
A risk calculator uses information such as age, family history, PSA value, the outcome of a digital rectal examination (DRE), and prostate volume to estimate the probability of finding (potentially aggressive) prostate cancer during a biopsy. These risk calculators give a result very fast but are less reliable because they only take into account clinical variables.
However, the genetic biomarker tests based on a sample of urine or blood from the patient gives a highly accurate individualised risk assessment for having aggressive disease and will lead to improved biopsy decision making.
Read here if you should discuss referral for MRI or conduct a biomarker test.
What are prostate biomarkers?
Biomarkers are biological molecules that are found in blood or urine. They are a patient specific and an objective measurement of a normal biological process (when present at normal levels) or a disease (when present at abnormal levels). They can help doctors in determining the risk of aggressive prostate cancer in men with an elevated PSA. As such, a biomarker test can help to decide to perform a biopsy and in turn avoid unnecessary biopsies.
Many biomarker tests are non-invasive as biomarkers are measured in a blood or urine sample. Biomarker tests can be repeated multiple times and can be done in both men with or without a prior prostate biopsy.
What are the advantages of new prostate cancer biomarkers?
In contrast to a PSA test, biomarker tests allow for the discrimination between prostate cancer and ‘benign’ prostate conditions such as prostatitis and BPH (adenoma). And because they also include genetic information from a patient, they are more reliable than traditional risk calculators.
The tests give an indication of the likelihood of finding cancer cells upon prostate biopsy and differentiate between insignificant and aggressive prostate cancer.
As with all tests, these biomarker tests also do not give you a 100% guarantee. However, one of newest tests, the SelectMDx urine test, for prostate cancer performs very well. When properly performed, this test has a negative predictive value of 95-98%, which means that, if the test is negative, you are 95-98% sure of not having aggressive prostate cancer [2,3].
What is SelectMDx?
SelectMDx is a new non-invasive urine test for determining the risk of (aggressive) prostate cancer. It measures the amount of two genes that are associated with aggressive prostate cancer. This is then combined with clinical information (age, PSA density, and the outcome of a digital rectal examination (DRE)) to calculate the risk of having aggressive cancer cells in your prostate.
So, SelectMDx gives an indication of the likelihood of having aggressive prostate cancer. If this likelihood is low, you can be 95-98% sure that you do not have aggressive prostate cancer and can consider to avoid an unnecessary biopsy
Read more about SelectMDx in the FAQ.
3. Haese A, Troostens G, Steyaert S, et al. Multicenter optimization and validation of a 2-gene mRNA urine test for detection of clinically significant prostate cancer before initial prostate biopsy. J Urol 2019;202:256-63
5. Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017;389:815-22
7. Poyet C, Nieboer D, Bhindi B, et al. Prostate cancer risk prediction using the novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) risk calculators: independent validation and comparison in a contemporary European cohort. BJU Int 2016;117:401-8
9. Hendriks RJ, van Oort IM, Schalken JA. Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions. Prostate Cancer Prostatic Dis 2017;20:12-9