Screening and Diagnostics Research
In recent years, the scope of prostate cancer research has expanded well beyond previous decades. Research in this field extends beyond clinical trials for new drugs or treatment options, and dives into discovering new biomarkers, screening tests, and much more. Several examples of investigational screening tests and prostate cancer-related research endeavors are described below.
A biomarker, as related to cancer research, is typically considered any sign of an unusual or abnormal process occurring in the body, and can be discovered in the blood, bodily fluids, or specific tissues. The PSA (prostate-specific antigen) test that is commonly used in the prostate cancer detection process is an example of a biomarker-dependent screening. Higher PSA levels have been associated with prostate cancer and other prostate-related conditions, and if present, can indicate a potential problem. Biomarkers include products secreted by tumors, as well as proteins and specific genes that indicate a cancer-related process may be occurring, such as unregulated cell growth and division.
Biomarkers are sought after for many reasons, including their ability to help diagnose a condition, as well as their potential ability to indicate the aggressiveness of a condition or predict an individual’s response to treatment options. Sometimes, biomarkers are used to determine if an individual is at a higher risk for developing a particular cancer, such as screening for inherited gene mutations in the BRCA1 and BRCA2 genes that could predispose an individual from developing early-onset prostate cancer. With all of this potential comes an increased desire to identify additional biomarkers and develop ways to investigate them non-invasively.
The PSA test is currently the main early screening tool used for prostate cancer, however, it has its shortcomings. For example, the PSA test is not able to specify aggressive versus relatively non-aggressive cancers, and can lead to over-diagnosis and over-treatment of prostate cancer. Additionally, the top of the normal range for PSA level is considered to be at 4 ng/ml, however, it has been estimated that roughly 20% of men with prostate cancer have PSA levels lower than this, while conversely, there are men with PSA levels higher than 4 ng/ml that do not have prostate cancer. Overall, the PSA test has its shortcomings, which has prompted researchers to look for a more reliable biomarker, especially for diagnostic purposes. Current research surrounds some of the following biomarkers:
- PHI (prostate health index): A test thought to distinguish between malignant prostate cancers and benign conditions of the prostate in men over 50 without any other significant prostate-cancer related findings (including a normal digital rectal exam and elevated PSA levels)
- PCA3 (prostate cancer antigen 3): Assesses the presence and level of a specific antigen related to prostate cancer, that is highly expressed in prostate cancer, and is thought to have a higher predictive value than the PSA test, but is less sensitive.
- Circulating tumor cells (CTC’s): Cells that can be detected in the blood that are indicative of a cancerous process occurring in the body. These cells carry genetic information and may predict cancers with worse survival potential.
- MicroRNA biomarkers: Small pieces of genetic information that may be present when cancer cells are present and growing. Could potentially predict the potential for recurrence, progression, and metastasis of a cancer, as well as its aggressiveness.
Other biomarker tests currently under investigation include the CCP signature, TMPRSS2-ERG gene fusion test, Mi-Prostate Score test, Oncotype DX test, ProMark test, ConfirmMDx test, Prolaris test, and the 4K score test, among others, with the potential to help diagnose prostate cancer, as well as predict its aggressiveness, potential response to treatment, recurrence risk, and more. However, until more solid evidence is found, the PSA test is still considered an early diagnostic standard.1-4
In addition to biomarkers, another area of research related to prostate cancer is the rising interest in better imaging methods. Current imaging methods, such as CT scans, MRIs, and bone scans, do not always meet the needs of providers and patients, especially when it comes to diagnosing prostate cancer or monitoring for its recurrence. One area of exciting research investigates the potential for 68Ga-PSMA-PET CT and MRIs. PSMA (prostate-specific membrane antigen) is a protein that gets overexpressed on prostate cancer cells. This means that PSMA is often found in high amounts around prostate cancer cells. PSMA is radioactively labeled, causing cells with lots of PSMA to light up on specific screens. One example of this screen can be performed with radioactive Gallium (68Ga).
Current investigations are pairing 68Ga-PSMA-PET with multiparametric MRI images to better localize cancer within the prostate as well as improve the detection of metastasis. It has even been theorized that these scans could detect metastasis even at low PSA levels, potentially finding aggressive or recurrent cancer well before other tests. The scan is so comprehensive that it may even be able to eliminate the need for multiple scans consecutively and reduce the amount of radiation or expensive tests a person may need to undergo.
Additionally, it has been theorized that the 68Ga-PSMA-PET scan can be used when biopsy or histological findings are normal, but prostate cancer is still suspected. By using prostate cancer-specific tracers, it’s possible to identify lesions with a high probability of containing prostate cancer cells, so that further biopsies can be better directed. Overall, many aspects of the diagnostic procedure may be able to be combined when using this scan, saving valuable time and money, as well as getting an improved view and idea of any cancer that is present, to better inform treatment options.5
As with many conditions, there are many clinical trials with both human and animal subjects dedicated to prostate cancer research. Some of these are investigating screening methods like the 68Ga-PSMA-PET CT and MRI scans, while other are comparing treatment options across different populations to determine the most efficient standards of care. Of course, there are also clinical trials dedicated to developing new medications to treat prostate cancer. Currently, over 140 phase III trials and over 650 phase I/II trials associated with treatment of prostate cancer are underway in the United States. There have been numerous new treatment options approved for prostate cancer in recent years as a result of clinical trials.
Several phase III trials are underway to assess treatment options like robot-assisted laparoscopic prostatectomies, as well as treatment options as they relate to an individual’s overall quality of life. Additionally, there are many new drugs currently being assessed in clinical trials.6,7