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Advances in Prostate Cancer Research

Nanoparticles are tested as a means to deliver drugs to prostate cancer cells.

Credit: National Cancer Institute

NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat prostate cancer.  Most men diagnosed with prostate cancer will live a long time, but challenges remain in choosing the best treatments for individuals at all stages of the disease.

This page highlights some of the latest research in prostate cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Studying Early Detection for Men at High Risk

Men with certain inherited genetic traits are at increased risk for developing prostate cancer. Examples of such traits include inherited BRCA gene mutations and Lynch syndrome. No clear guidelines exist for when or how—or if—to screen men at high genetic risk for prostate cancer. 

NCI researchers are using magnetic resonance imaging (MRI) of the prostate in men at high risk to learn more about how often and how early these cancers occur. They’re also testing whether regular scans in such men can detect cancers early, before they spread elsewhere in the body (metastasize).

Diagnosing Prostate Cancer

Improving Biopsies for Prostate Cancer

Traditionally, prostate cancer has been diagnosed using needles inserted into the prostate gland in several places under the guidance of transrectal ultrasound (TRUS) imaging to collect samples of tissue. This approach is called systematic biopsy.

However, ultrasound does not generally show the location of cancer within the prostate. It is mainly used to make sure the biopsy needles go into the gland safely. Therefore, biopsy samples using ultrasound guidance can miss cancer altogether, or identify low-grade cancer while missing areas of high-grade, potentially more aggressive cancers.

Some doctors, concerned that a systematic biopsy showing only low-grade cancer could have missed a high-grade cancer, may suggest surgery or radiation. However these treatments are for a cancer that may have never caused a problem, which is considered overtreatment.

Using MRI and ultrasound. Scientists at NCI have developed a procedure that combines magnetic resonance imaging (MRI) with TRUS for more accurate prostate biopsies. MRI can locate potential areas of cancer within the gland but is not practical for real-time imaging to guide a prostate biopsy. The new procedure, known as MRI-targeted biopsy, uses computers to fuse an MRI image with an ultrasound image. This lets doctors use ultrasound guidance to biopsy areas of possible cancer seen on MRI.

NCI researchers have found that combining MRI-targeted biopsy with systematic biopsy can increase the detection of high-grade prostate cancers while decreasing detection of low-grade cancers that are unlikely to progress. 

Testing machine learning. Researchers are testing the use of machine learning, also called artificial intelligence (AI), to better recognize suspicious areas in a prostate MRI that should be biopsied. AI is also being developed to help pathologists who aren't prostate cancer experts accurately assess prostate cancer grade. Cancer grade is the most important factor in determining the need for treatment versus active surveillance.

Finding Small Amounts of Prostate Cancer Using Imaging and PSMA

NCI-supported researchers are developing new imaging techniques to improve the diagnosis of recurrent prostate cancer. A protein called prostate-specific membrane antigen (PSMA) is found in large amounts—and almost exclusively—on prostate cells. By fusing a molecule that binds to PSMA to a compound used in PET scan imaging, scientists have been able to see tiny deposits of prostate cancer that are too small to be detected by regular imaging. The Food and Drug Administration (FDA) has approved two such compounds for use in PET imaging of men with prostate cancer.

This type of test is still experimental. But the ability to detect very small amounts of metastatic prostate cancer could help doctors and patients make better-informed treatment decisions. For example, if metastatic cancer is found when a man is first diagnosed, he may choose an alternative to surgery because the cancer has already spread. Or doctors may be able to treat cancer recurrence—either in the prostate or metastatic disease—earlier, which may lead to better survival.

As part of the Cancer Moonshot℠, NCI researchers are testing whether PSMA-PET imaging can also identify men who are at high risk of their cancer recurring. Such imaging may eventually be able to help predict who needs more aggressive treatment—such as radiation therapy in addition to surgery—after diagnosis. 

Prostate Cancer Treatment

Treatments for prostate cancer that has not spread elsewhere in the body are surgery or radiation therapy (RT), with or without hormone therapy. Active surveillance is also an option for men who have a low risk of their cancer spreading.

Hormone Therapy for Prostate Cancer

Over the last few years, several new approaches to hormone therapy for advanced or metastatic prostate cancer have been approved for clinical use.

Many prostate cancers that originally respond to treatment with standard hormone therapy become resistant over time, resulting in castrate-resistant prostate cancer (CRPC). Three new drugs have been shown to extend survival in men with CRPC. All three block the action of hormones that drive CRPC:

The survival benefit for these drugs has been seen regardless of whether men have previously received chemotherapy.

In addition, both enzalutamide and the drug apalutamide (Erleada) have all been shown to decrease the risk of metastases in men with CRPC that has not yet spread to other parts of the body. Darolutamide has been shown to increase the amount of time men live without their cancer metastasizing.

Abiraterone, apalutamide, and enzalutamide have been shown to improve the survival of men with metastatic castrate-sensitive prostate cancer when added to standard hormone therapy.

Scientists are continuing to study novel treatments and drugs, along with new combinations of existing treatments, in men with metastatic CRPC.

Immunotherapy: Vaccines for Prostate Cancer

Immunotherapies are treatments that harness the power of the immune system to fight cancer. These treatments can either help the immune system attack the cancer directly or stimulate the immune system in a more general way.

Vaccines and checkpoint inhibitors are two types of immunotherapy being tested in prostate cancer. Treatment vaccines are injections that stimulate the immune system to recognize and attack a tumor.

One type of treatment vaccine called sipuleucel-T (Provenge) is approved for men with few or no symptoms from metastatic CRPC.

Immunotherapy: Checkpoint Inhibitors for Prostate Cancer

An immune checkpoint inhibitor is a type of drug that blocks proteins on the immune cells, making the immune system more effective at killing cancer cells.

A checkpoint inhibitor called pembrolizumab (Keytruda) has been approved for the treatment of tumors, including prostate cancers, that have specific genetic features. Pembrolizumab has also been approved for any tumor that has metastasized and has a high number of genetic mutations.

But relatively few prostate cancers have these features, and prostate cancer in general has largely been resistant to treatment with checkpoint inhibitors and other immunotherapies, such as CAR T-cell therapy.

Research is ongoing to find ways to help the immune system recognize prostate tumors and help immune cells penetrate prostate tumor tissue. Studies are looking at whether combinations of immunotherapy drugs, or immunotherapy drugs given with other types of treatment, may be more effective in treating prostate cancer than single immunotherapies alone.

PARP Inhibitors for Prostate Cancer

Some prostate tumors have genetic defects that limit their ability to repair DNA damage. Such tumors may be sensitive to a class of drugs called PARP inhibitors, which also block DNA repair. 

Two PARP inhibitors, olaparib (Lynparza) and rucaparib (Rubraca), have been approved for some men whose prostate cancer has metastasized, and whose disease has stopped responding to standard hormone treatments.

Targeted Radiation Therapy and PSMA

Scientists are also developing targeted therapies based on PSMA, the same protein that is being tested for imaging prostate cancer. For treatment, the molecule that targets PSMA is chemically linked to a radioactive compound. This new compound can potentially find, bind to, and kill prostate cancer cells throughout the body.

In a recent clinical trial, men with a type of advanced prostate cancer who received a PSMA-targeting drug lived longer than those who received standard therapies. Ongoing and planned clinical trials are testing PSMA-targeting drugs in patients with earlier stages of prostate cancer, and in combination with other treatments, including targeted therapies like PARP inhibitors and immunotherapy.

Personalized Clinical Trials for Prostate Cancer

Research is uncovering more information about the genetic changes that happen as prostate cancers develop and progress. Although early-stage prostate cancer has relatively few genetic changes compared with other types of cancer, researchers have learned that metastatic prostate cancers usually accumulate more mutations as they spread through the body.

These mutations may make men with metastatic prostate cancers candidates for what are called “basket” clinical trials of new drugs. Such trials enroll participants based on the mutations found in their cancer, not where in the body the cancer arose. In the NCI-MATCH trial, a high percentage of enrolled men with advanced prostate cancer had mutations that could potentially be targeted with investigational drugs.

NCI-Supported Research Programs

See a full list of prostate cancer research projects that NCI funded in FY 2018.

Many NCI-funded researchers working at the National Institutes of Health campus, as well as across the United States and world, are seeking ways to address prostate cancer more effectively. Some of this research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in prostate cancer.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for prostate cancer prevention, screening, and treatment.

Prostate Cancer Research Results

The following are some of our latest news articles on prostate cancer research:

View the full list of Prostate Cancer Research Results and Study Updates.

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