Diagnosing Prostate Cancer
Traditionally, prostate cancer has been diagnosed using a biopsy: needles are inserted into the prostate gland in several places under the guidance of transrectal ultrasound (TRUS) imaging to collect samples of tissue.
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 TRUS 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 a fusion 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.
In a recent clinical trial, the PRostate Evaluation for Clinically Important Disease (PRECISION) trial, an MRI-targeted biopsy approach was more successful in detecting higher-grade cancers that were likely to require treatment than biopsies guided by ultrasound alone. Fusion biopsy was also better at identifying low-grade cancers that were not likely to require treatment.
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 tested to improve the analysis of biopsy samples to more accurately determine which cancers need to be treated and which could be managed using active surveillance.
Pinpointing Recurrent Prostate Cancer
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 ability to detect very small amounts of metastatic prostate cancer could help doctors and patients make better-informed treatment decisions. For example, if small amounts of metastatic cancer are found when a man is first diagnosed, he may choose hormone therapy instead of surgery, since 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.
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.
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). Two new drugs have been shown to extend survival in men with CRPC:
The survival benefit for these drugs has been seen regardless of whether men have previously received chemotherapy.
Both abiraterone and apalutamide have also been shown to increase 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.
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.
One type of treatment vaccine called sipuleucel-T (Provenge) is approved for men with few or no symptoms from metastatic CRPC.
Another prostate cancer treatment vaccine, rilimogene-galvacirepvec (PROSTVAC), was developed at NCI and is being tested in clinical trials. PROSTVAC has not been shown to improve the survival of men with metastatic disease. However, other trials are evaluating the effects of this vaccine in earlier stages of prostate cancer.
For example, PROSTVAC is being studied in men with localized prostate cancer who have chosen active surveillance. The goal of the trial is to see if the vaccine can cause immune cells to recognize and attack early prostate tumors. If it does, PROSTVAC may be tested for secondary prevention: preventing early cancer from progressing to more aggressive disease.
Studies are also testing PROSTVAC in combination with other immunotherapies or chemotherapy for metastatic cancer.
Immunotherapy: Checkpoint Inhibitors
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. But few prostate cancers have these genetic 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.
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. An ongoing randomized clinical trial is testing a PARP inhibitor in men whose tumors are deficient in DNA repair. Future trials may test PARP inhibitors in combination with hormone therapy or other treatments.
Targeted Radiation Therapy
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. Early clinical trials of this method of targeting PSMA are under way.
Personalized Clinical Trial Enrollment
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.