A prostate biopsy is the only definitive way for your doctor to confirm whether you have prostate cancer. Once you and your doctor have decided that a prostate biopsy should be performed, a post-biopsy follow-up clinic visit will be scheduled to discuss the results. If there is no cancer, your doctor will talk with you about follow-up appointments. These include follow-up PSA blood tests and possibly prostate MRI imaging. If there is prostate cancer on the biopsy, your doctor may recommend treatment. Treatment recommendations may include a radical prostatectomy (surgery to remove the prostate gland), radiation therapy, or active monitoring (also called active surveillance).
Your doctor’s recommendation will depend on many factors including PSA at the time of biopsy, Gleason score, and your overall health. In certain situations, it may be helpful to understand more about your prostate cancer to help guide treatment strategies.
One such strategy is the use of biomarkers in the post-prostate biopsy setting. Biomarkers are special molecules found in blood or tissue that can help your doctor find out if you have cancer or not. They help to further clarify risk. The risks may include:
- Prostate cancer in the prostate gland even after a negative biopsy
- Tumor aggressiveness
- Recurrence after treatment, etc.
In prostate cancer, biomarkers in the post-biopsy setting are tests that are done on the prostate tissue removed during the biopsy, and in some situations on the whole prostate gland after a radical prostatectomy. The following list represents the available biomarkers that may be used to guide further monitoring and/or treatment after a prostate biopsy has been performed:
- ConfirmMDx: For men who have previously had a negative (no cancer) prostate biopsy, this biomarker can test the tissue from the first biopsy to check for changes that may suggest prostate cancer in other areas of the prostate that were not biopsied. This process is called “epigenetic changes,” which assesses for hypermethylation of GSPT1, APC, and RASSF1.
- Prolaris: This test measures tumor biology (providing a cell-cycle progression score) that improves the accuracy of risk stratification for men that have been diagnosed with localized prostate cancer. Specifically, this test combines the RNA (part of your genetic material) expression levels of 31 genes involved in prostate cancer progression + 15 other “housekeeping” genes to generate the Prolaris Score. The Prolaris test has been used to guide doctors and patients as to who may be an appropriate candidate for active surveillance, as well as those that should receive definitive treatment.
- Oncotype Dx: Also known as the OncotypeDx Genomic Prostate Score , OncotypeDx improves risk stratification in men with newly diagnosed prostate cancer. This test utilizes RNA expression levels of 12 prostate cancer genes and 5 reference genes to generate the GPS (scale of 0 to 100). Additionally, when this test is used on the whole prostate gland after a radical prostatectomy, OncotypeDx provides a risk of biochemical recurrence (PSA increasing in the blood) after the prostate is removed among men with low and intermediate-risk prostate cancer.
- ProMark: Among men with Gleason 3 + 3 and Gleason 3 + 4 prostate cancer on a prostate biopsy, this biomarker is a protein-based test that predicts the aggressiveness of a patient’s cancer. ProMark uses a “signature” of 8 proteins to provide a score of 0 to 1. It also predicts the risk of adverse pathology (high-risk disease) at the time of radical prostatectomy.
- Decipher: Arguably the biomarker with the most robust evidence is the Decipher genomic classifier, which measures RNA expression of 22 different genes. Similar to OncotypeDx and ProMark, Decipher is available for testing on prostate biopsy tissue and radical prostatectomy whole prostate specimens. Of note, Decipher is specifically mentioned in the National Cancer Comprehensive Network (NCCN) guidelines as an approved biomarker for risk stratification. In addition to being useful for local therapy planning for newly diagnosed localized prostate cancer patients, Decipher provides several important pieces of information among patients who have had a radical prostatectomy:
- Likelihood/timing of post-radical prostatectomy salvage radiation therapy
- Predicting clinical metastases (disease spreading outside of the prostate bed after surgery) for patients with biochemical recurrence after surgery
- Likelihood of clinical metastases within 5 and 10 years after radical prostatectomy for men with high-risk pathology after surgery
Deciding whether to utilize one or more of these biomarkers after a prostate biopsy (or after a radical prostatectomy) to help determine surveillance intensity and other treatment decisions should be discussed in a shared decision-making approach between you and your doctor. In many cases, biomarkers will not be needed to make the right decisions. However, in some cases, this additional information may be valuable. There may be enough evidence that primary therapy (after a prostate biopsy) or salvage therapy (after primary therapy has failed) is needed even without a biomarker test. It is important to realize that all of these biomarkers may not be available at your doctor’s institution or may not be covered by your insurance, leading to out-of-pocket costs.
What is Genomic Testing for Prostate Cancer?
Men with high-risk localized prostate cancer require intensive treatment of their cancer in order to diminish the risk of dying of prostate cancer. Over the last five to 10 years, genomic testing has evolved to try and “personalize” the treatment of prostate cancer.
Genomic testing takes on two forms:
(1) looking at the genes you were born with, that are found in every cell in your body (i.e., your DNA, or “what makes you who you are”), or
(2) looking at cancer genes in the prostate tumor itself. The first type of testing is called “germline testing” and the second type is called “somatic testing.” Germline testing is typically done from a blood test or a saliva sample, whereas somatic testing is done from biopsy tissue from the prostate or from one of the sites that prostate cancer has spread to (i.e., the bones, liver, lungs, lymph nodes). One of the most common germline genomic tests is the FoundationOne Liquid CDX test, which is an FDA-approved test that analyzes genes from a simple blood test, in addition to being the only approved blood test to analyze over 300 genes.
Genomic testing helps doctors see how DNA and genes work within the cell and can suggest a path to better treat your cancer. Furthermore, genomic testing may be able to answer other questions, such as:
- Will your cancer grow slowly or will it get worse quickly?
- Is your cancer likely to spread?
- What types of treatment should we use to treat your prostate cancer?
In other articles, we discuss how genomics makes up the basis for pre- and post-prostate biopsy biomarkers. In this article, we focus on genomic testing that identifies certain genes that may provide further information for cancer aggressiveness and for guiding treatment. It is important to understand who is most likely to benefit from either germline or somatic genomic testing. The National Comprehensive Cancer Network (NCCN) suggests that all of the following men with prostate cancer should be considered for genomic testing:
- A family history of prostate cancer
- High and very high risk localized prostate cancer
- Locally advanced and metastatic prostate cancer
- Ashkenazi Jewish ancestry
- Intraductal or cribriform (particularly aggressive cells on microscopic examination on prostate biopsy tissue) prostate cancer
Furthermore, it is important to understand how genomic testing may guide treatment plans. For men who have had surgery, it may help with understanding their risk of recurrence in the future. This may be important to guide the early use of subsequent treatments (like radiation or hormone therapy). For men with advanced prostate cancer (specifically metastatic castration-resistant prostate cancer (mCRPC), medications called PARP inhibitors (specifically called olaparib and rucaparib) are FDA-approved for those patients who have certain genetic mutations in genes that repair damaged DNA, including mutations in BRCA1 and BRCA2. These genetic mutations may sound familiar, as they are famously known for their association with aggressive breast and ovarian cancer. They also are associated with aggressive prostate cancer. For men with MSI-high mutations in their prostate tumor (which is quite rare, with only ~3% of prostate cancers having this mutation), the immunotherapy agent pembrolizumab is approved for these patients, which is typically associated with the mCRPC disease state.
In conclusion, men with high risk-localized prostate cancer should discuss with their cancer doctors the utility of genomic testing. Based on real-world studies, unfortunately, genomic testing of a patient’s blood or their tumors has not had the uptake that would be expected, thus it is important for patients to specifically ask their doctor if genomic testing is appropriate for them. As highlighted above, genomic testing may be important for personalizing treatment, particularly for men with advanced prostate cancer.
Magnetic resonance imaging (MRI) is a type of imaging, or way to take pictures of the inside of the body. It creates images with a magnetic field and computer-generated radio waves. The MRI machine is a large tube-shaped structure that you lie inside. For prostate cancer imaging, the machine will take pictures of your pelvis (lower abdomen), including your prostate gland.
Why would I get a prostate MRI?
There are several reasons why your doctor may order an MRI to help them with staging and planning treatment for your prostate cancer.
When Considering Prostate Biopsy After an Elevated PSA
If your PSA blood test (a screening test for prostate cancer) is elevated or high, your urologist may order a prostate MRI before considering a prostate biopsy (to see if you have prostate cancer). There are several large clinical studies that show that men who have an elevated PSA and receive an MRI before getting a biopsy benefit in at least two ways.
First, some men may have such a good result from their MRI that a biopsy is not needed right away. However, a “normal” MRI does not guarantee there is no prostate cancer. So, you should still talk with your urologist about whether or not you need a prostate biopsy.
Second, the MRI provides a “map of the prostate” to guide a urologist to perform targeted biopsies of those areas most likely to have prostate cancer. As a result, these studies have shown that clinically significant prostate cancer (that which requires treatment) is more likely to be found in men who have an MRI before biopsy.
During Active Surveillance for Low-Grade/Low Volume Prostate Cancer
There are many protocols that doctors may follow when patients are on active surveillance. However, nearly all modern protocols use prostate MRI at some point in the active surveillance journey. Patients that are being considered for active surveillance most often have an MRI soon after their first biopsy. This is done to see if there are areas in the prostate that should be targeted at the time of the second, or confirmation, biopsy. For men that have been on active surveillance, most doctors will perform an MRI every one to two years to make sure there are no changes in how the prostate looks on MRI.
Local Staging for High-Risk Prostate Cancer
Prior to local therapy (i.e., surgery or radiotherapy) for high-risk prostate cancer, your doctor may order an MRI to get a better look at the anatomy of the prostate. The MRI will also help your doctor see the areas around the prostate, such as any enlarged lymph nodes (which is a common location for prostate cancer to spread).
Specifically, for patients who will have surgery, a prostate MRI may allow your urologist to see if prostate cancer is close to the prostate capsule (the wall of the prostate gland). This information can help your urologist to plan how much nerve-sparing can or should be done for each side of the prostate gland during the operation. Your urologist can be better prepared to do the cancer operation and provide you with the best chance to return to your normal life as much as possible.
What does a prostate MRI involve?
During an MRI, you will lie on the narrow bed of the MRI machine while it moves in and out of the MRI tube. This process takes about 30 minutes. In most cases, you will receive contrast dye through an I.V. during the scan.
Some men are claustrophobic (afraid of small spaces) and may find being in the MRI “tube” hard to tolerate. If you are claustrophobic, you should mention this to your doctor. They may prescribe a light sedative or a medication (i.e., Valium) to help ease the anxiety of the MRI.
Before the MRI you must remove any clothing with snaps or zippers. You likely will be asked to wear a hospital gown in the MRI scanner. Additionally, you should take off any jewelry or metal, including hearing aids.
There are several absolute contraindications (i.e., reasons why you should NOT have an MRI) to receiving an MRI. These include having a cardiac implantable electronic device (CIED) such as a pacemaker, an implantable cardioverter defibrillator (ICDs), and cardiac resynchronization therapy (CRT) device. Patients who have one of these devices are at risk of device malfunction (not working right), device heating/movement, and possible irregular heartbeat (arrhythmia) during an MRI.
If you have an elevated or high PSA test, an MRI may help your urologist to check to see if and where cancer may be in your prostate. The results of the MRI will help your urologist plan the next steps of your prostate cancer journey, and guide you and your loved ones in shared decision-making.