A biological marker, or biomarker, is a measurable substance or characteristic within the body that indicates a particular condition. For prostate cancer, these markers are proteins, genes, or other substances offering clues about the presence of cancer. They are not a diagnosis, but tools used to assess risk and guide medical decisions.
Information from these markers helps doctors understand the likelihood of cancer, its potential aggressiveness, or how it might respond to treatment. Testing is often done through “liquid biopsies,” which are analyses of fluids like blood or urine. This approach provides information in a less invasive way than tissue sampling.
The Role of Prostate-Specific Antigen
Prostate-Specific Antigen (PSA) is a protein produced by cells in the prostate gland, which creates fluid for semen. While most PSA is in semen, small amounts circulate in the bloodstream and can be measured with a blood test. This test is a primary method for prostate cancer screening.
The PSA test detects elevated levels of this protein, which can indicate a problem with the prostate, including cancer. While 4.0 nanograms per milliliter (ng/mL) was once a common cutoff, this is not a strict line. A typical level is influenced by factors like age, as PSA levels naturally rise as men get older.
A high PSA reading does not automatically mean cancer is present, as several non-cancerous conditions can increase PSA levels. These include benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the prostate, and prostatitis, an inflammation or infection of the gland. Recent ejaculation or vigorous exercise like cycling can also affect the results.
Interpreting PSA Test Results
Because a single PSA number provides limited information, physicians consider it in a broader context. One method is PSA density, which compares the PSA level to the prostate’s volume. A higher PSA density (above 0.15 ng/mL/cm³) can be more suggestive of cancer, as it indicates a smaller gland is producing a disproportionately high amount of PSA.
PSA velocity tracks how quickly the PSA level changes over time. A rapid increase, such as a rise of more than 0.35 ng/mL in a year, is more concerning than a stable but elevated value. Establishing a reliable trend requires at least three measurements over about 18 months.
Clinicians also analyze the ratio of “free PSA” to “total PSA.” In the blood, PSA is either bound to proteins or circulates freely. Prostate cancer tends to produce more of the bound form, lowering the percentage of free PSA. A free PSA level below 10% suggests a higher cancer risk, while a level above 25% points toward a benign condition.
These detailed interpretations are necessary due to the PSA test’s limitations. The test has a high rate of false positives, where elevated levels lead to further procedures even when no cancer is present. It can also produce false negatives, missing about 15% of prostate cancers, and lead to the overdiagnosis of slow-growing cancers that may not have caused harm.
Advanced and Secondary Markers
When PSA results are unclear, doctors may use advanced markers to clarify risk and determine if a biopsy is needed. These tests provide a more detailed assessment than a standard PSA test alone.
Blood and Urine Markers
Blood-based panels combine several markers into a single risk score. The Prostate Health Index (phi) measures total PSA, free PSA, and a precursor form called proPSA. The 4Kscore test assesses four different kallikrein proteins in the blood along with clinical factors. Other tests analyze urine for specific genetic material after a digital rectal exam. The PCA3 test measures an mRNA molecule over-expressed in prostate cancer cells, while the SelectMDx test looks for two mRNA biomarkers to predict the likelihood of detecting aggressive cancer.
Genetic and Genomic Markers
Genetic tests can identify inherited gene mutations, like those in the BRCA1 and BRCA2 genes, which indicate a higher lifetime risk of developing the disease. After a biopsy confirms a cancer diagnosis, tissue-based genomic markers like Prolaris and Decipher can be used. These tests analyze gene activity within the cancerous tissue to help predict the cancer’s aggressiveness and guide treatment decisions.
From Marker to Diagnosis
If marker tests indicate a high probability of cancer, the next step is obtaining a diagnosis. This process begins with advanced imaging, most commonly a multi-parametric MRI (mpMRI). This scan provides detailed images of the prostate, allowing doctors to identify suspicious areas. Findings are reported using a scoring system, like PI-RADS, where a higher score indicates a greater likelihood of cancer.
A prostate biopsy is the standard for diagnosis. In this procedure, a physician obtains small tissue samples from the prostate with a thin needle. Modern techniques often use an MRI-fusion biopsy, where mpMRI images are fused with live ultrasound to guide the needle to suspicious areas. This targeted approach is more accurate at detecting high-risk cancers than a standard biopsy.
A pathologist examines the tissue samples to determine if cancer cells are present. If cancer is found, it is graded using the Gleason scoring system. This system assesses the cancer’s aggressiveness based on how much the cells differ from normal tissue, with scores from 6 (low-grade) to 10 (high-grade). This score informs treatment planning.