Why biomarker tests?
Today’s challenges in prostate cancer diagnosis
Currently, the decision to biopsy and diagnosis of prostate cancer relies mainly on PSA and DRE. However, due to the low specificity of PSA for (high-grade) cancer, there is a significant risk of overdiagnosis since many men are diagnosed with clinically insignificant cancer. In turn, this may lead to (over)treatment of insignificant disease. Moreover, many men have a negative biopsy and are unnecessarily exposed to anxiety, pain and potential complications related to biopsy . It should also be noted that although biopsy remains the gold standard for the diagnosis of prostate cancer, a 10-12 core biopsy samples only a small (<1%) part of the prostate and clinically significant cancer may be missed.
One of the major challenges in the urologic field is how to identify men who need a biopsy and, more specifically, those who harbour an increased risk of having clinically significant prostate cancer. Finding these men at high risk of significant cancer is essential as they will mostly benefit from earlier diagnosis and treatment. At the same time, it is important to reduce the number of unnecessary invasive biopsies in men without (clinically significant) cancer.
Biomarker tests: the answer to the challenges in prostate cancer diagnosis
Biomarker tests help to improve the early diagnosis of prostate cancer. This is because they aim to identify men at risk of harbouring clinically significant cancer who need a biopsy, and who may benefit from earlier diagnosis and treatment. Men at low risk of having clinically significant cancer can be spared an unnecessary biopsy and associated risk of anxiety, pain and complications. Ideally, a biomarker test has no or a very low risk of missing clinically significant cancer.
- To identify men at increased risk of harbouring clinically significant cancer who may benefit from earlier diagnosis and treatment
- To avoid the risk of missing the detection of clinically significant cancer
- To avoid the number of unnecessary biopsies with associated complications and costs
Biomarker tests and their use
From the early 1990s, there has been an increasing interest in diagnostic biomarker tests as they may help to find clinically significant cancer. The early tests, such as PCA3 and the Prostate Health Index (PHI), generally only consist of molecular biomarkers. They usually predict overall prostate cancer on biopsy although some studies suggest that PCA3 and PHI correlate with features of prostate cancer significance.
The new generation tests evolved to specifically predicting clinically significant prostate cancer. These tests, including the 4Kscore, ConfirmMDx, MiPS, and SelectMDx, are usually risk scores including both biomarkers and clinical information.
Diagnostic biomarker tests can help to find men at risk of harbouring (clinically significant) cancer in need for a biopsy. They can be used to determine who needs an initial biopsy and who not. Biomarker tests can also help identify men in need for a repeat biopsy. These men had a prior negative biopsy but there is still a persistent suspicion of prostate cancer.
Difference between biomarker tests
When a diagnostic biomarker test is negative, it is important that the risk of missing (clinically significant) cancer is minimal. This is described by the negative predictive value (NPV): the proportion of men with a negative test result that do not have the disease. The NPV value needs to be as high as possible.
New generation biomarker tests have a very high NPV (95-98%). This means that they have a minimal risk of missing clinically significant cancer (2-5%). In comparison, old generation biomarker tests have a much lower NPV (67-92%) leading to a higher risk of missing cancer (8-33%).
There are no data from prospective, randomised trials comparing the accuracy of different biomarker tests in detecting clinically significant prostate cancer. However, an indirect comparison of all tests suggests that SelectMDx has the best outcome: a very high accuracy of finding clinically significant cancer with only a 2% risk of missing significant cancer in case of a negative test result (see table).
What is SelectMDx?
SelectMDx helps you find clinically significant cancer. It is a diagnostic test that helps distinguish men at increased risk for significant prostate cancer from those at very low risk. SelectMDx can guide the decision for performing a biopsy.
SelectMDx is a non-invasive, urine-based test that measures the expression of 2 mRNA cancer-related biomarkers (HOXC6 and DLX1). This is combined with PSA, PSA density, DRE, age, and family history of prostate cancer into a risk score.
SelectMDx is CE-marked and available in most EMEA countries and the USA.
Development and validation of SelectMDx
SelectMDx was developed and validated in a prospective, multicenter study using 2 independent cohorts of men scheduled for prostate biopsy :
- Before biopsy, post-DRE urine was collected and mRNA levels of several biomarkers were measured. The combination of HOXC6 and DLX1 had the highest predictive accuracy (AUC 0.76) for high-grade prostate cancer (Gleason score ≥7). From a previous study, it was also shown that these biomarkers have a higher predictive accuracy for high-grade prostate cancer than PCA3 .
- Subsequently, logistic regression models were developed and validated combining the biomarkers with clinical variables (PSA, PSA density, DRE, age, family history and prior biopsy).
- SelectMDx had a very high predictive accuracy (AUC 0.87) for high-grade prostate cancer, which was significantly better than the Prostate Cancer Prevention Trial (PCPT) risk calculator version 2 (AUC 0.77; P=0.015) [2,3].
Benefits of SelectMDx
- SelectMDx identifies men at high risk of having clinically significant cancer. These men may benefit from earlier diagnosis and treatment
- SelectMDx has a very high NPV of 98%. This means that if the test is negative, the patient can be 98% sure that he doesn’t have clinically significant (Gleason score ≥7) prostate cancer. The risk of missing high-grade (Gleason score ≥7) prostate cancer is only 2% . This provides reassurance for your patients. Of note, SelectMDx had a NPV of 99.6% for Gleason score ≥8 cancer
- SelectMDx has a very high predictive accuracy for high-grade prostate cancer (AUC 0.87), which was significantly better than the PCPT risk calculator version 2 (AUC 0.77; P=0.015) [2,3]
- SelectMDx is a non-invasive, urine-based test
Clinical utility of SelectMDx
SelectMDx helps distinguish men with a high likelihood for high-grade prostate cancer upon biopsy from men at very low risk (with a 98% NPV).
- Men at high risk may benefit from biopsy, early detection and treatment.
- Men at very low risk may avoid unnecessary invasive biopsy procedures and the associated risk of anxiety, pain and complications.
Would you like to know more about the use of biomarkers in clinical practice? Click here
How to use SelectMDx?
Instructions for use
To apply the SelectMDx test you have to follow 12 simple steps:
- Perform a DRE (3 strokes per lobe) to mobilise the prostate cancer cells and exosomes towards the urethra. Apply enough pressure to slightly depress the prostate surface (it is not intended to be a prostate massage)
Collect first voided urine immediately following the DRE. Use the UrNCollect device provided in your SelectMDx Urine Collection kit
Remove the UrNCollect Funnel and Tube from the box
Place the Tube upright on a flat surface and unscrew the cap (do not throw away the cap as it will be used later)
Hold the Funnel upright and screw on the Tube
Instruct the patient to point the spout of the device towards the toilet and urinate into the Funnel; the patient should continue urinating until the bladder is completely empty
Unscrew the Tube from the Funnel. Gently tab floater against the inside of the Tube
Firmly screw the cap onto the Tube and invert the tube 5 times to mix the content
Place the barcode label on the Tube and Test Requisition Form
Place the Tube into the Safety bag
Place the sealed Safety bag with the Test Requisition Form in the SelectMDx Urine Collection kit
Ship the box at ambient temperature as soon as possible after collection (it must reach the laboratory of MDxHealth BV within 5 days of collection)
Discover the physician's brochure
SelectMDx should be performed only when serum PSA has been determined less than 6 months ago.
SelectMDx should be performed only after 3 months in men who had:
- a prostate biopsy
- a transurethral resection of the prostate (TURP)
SelectMDx should be interpreted with caution in men:
- taking 5α-reductase inhibitors (e.g. Proscar®, Avodart®)
- having a urinary tract infection
SelectMDx is not influenced by prostatitis and Benign Prostatic Hyperplasia (BPH).
SelectMDx patient report
The patient report indicates the likelihood of detecting prostate cancer in the biopsy, including the probability of high-grade (Gleason score ≥7) prostate cancer.
3. Based on data published by Van Neste et al. Eur Urol 2016;70:740-8.
4. 4Kscore Test Characteristics, available at http://4kscore.com/wp-content/uploads/2016/09/Interpreting-your-Results.pdf (last accessed May 2017)
5. Parekh DJ, Punnen S, Sjoberg DD, et al. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol 2015;68:464-70.
8. Gittelman M, Hertzman B, Bailen J, et al. PROGENSA®PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. J Urol 2013;190:64-9.