What’s new in prostate cancer research and treatment?

Research into the causes, prevention, detection, and treatment of prostate is going on in many medical centers throughout the world.

Genetics

New research on genes linked to prostate cancer is helping scientists better understand how prostate cancer develops. This research will help provide answers about the genetic changes that lead to prostate cancer. This could make it possible to design medicines to target those changes. Tests to find abnormal prostate cancer genes could also help identify men at high risk who would benefit from more intensive screening or from chemoprevention trials, which use drugs to try to keep them from getting cancer.

Most of the genes that have been studied so far are from chromosomes that are inherited from both parents. Some research has found that a certain variant of mitochondrial DNA, which is inherited only from a person's mother, might double or even triple a man's risk of developing prostate cancer.

One of the biggest problems now facing men with prostate cancer and their doctors is figuring out which cancers are likely to stay within the gland and which are more likely to grow and spread (and definitely need treatment). New discoveries may help with this some time in the near future. For example, the product of a gene known as EZH2 seems to appear more often in advanced prostate cancers than in those at an early stage. Researchers are now trying to decide whether the presence of this gene product, or others, indicates that a cancer is more aggressive. This could eventually help tell which men need treatment and which might be better served by active surveillance.

Prevention

Researchers continue to look for foods (or substances in them) that can help lower prostate cancer risk. Scientists have found some substances in tomatoes (lycopenes) and soybeans (isoflavones) that might help prevent prostate cancer. Studies are now looking at the possible effects of these compounds more closely. Scientists are also trying to develop related compounds that are even more potent and might be used as dietary supplements. So far, most research suggests that a balanced diet including these foods as well as other fruits and vegetables is of greater benefit than taking these substances as dietary supplements.

Some studies have suggested that certain vitamin and mineral supplements (such as vitamin E and selenium) might lower prostate cancer risk. But a large study of this issue, called the Selenium and Vitamin E Cancer Prevention Trial (SELECT), found that neither vitamin E nor selenium supplements lowered prostate cancer risk after daily use for about 5 years. In fact, men taking the vitamin E supplements were later found to have a slightly higher risk of prostate cancer.

Another vitamin that may be important is vitamin D. Recent studies have found that men with high levels of vitamin D seem to have a lower risk of developing the more lethal forms of prostate cancer. Overall though, studies have not found that vitamin D protects against prostate cancer.

Many people assume that vitamins and other natural substances cause no harm, but recent research has shown that high doses may be harmful, including those supplements marketed specifically for prostate cancer. For example, one study found that men who take more than 7 multivitamin tablets per week may have an increased risk of developing advanced prostate cancer.

Scientists have also tested certain hormonal medicines called 5-alpha reductase inhibitors as a way of reducing prostate cancer risk. The results of these studies were discussed in the section, "Can prostate cancer be prevented?"

Early detection

Doctors agree that the prostate-specific antigen (PSA) blood test is not a perfect test for finding prostate cancer early. It misses some cancers, and in other cases it is elevated when cancer isn't present. Researchers are working on two strategies to address this problem.

One approach is to try to improve on the test that measures the total PSA level, as described in the section, "Can prostate cancer be found early?" The percent-free PSA is one way to do this, although it requires two separate tests. Another option might be to measure only the "complexed" PSA (the portion of PSA that is not "free") to begin with, instead of the total and free PSA. This one test could give the same amount of information as the other two done separately. Studies are now under way to see if this test provides the same level of accuracy.

The other approach is to develop new tests based on other tumor markers. Several newer blood tests seem to be more accurate than the PSA test, based on early studies. Early results have been promising, but these and other new tests are not yet available outside of research labs and will need more study before they are widely used to test for prostate cancer.

Other new tests being studied are urine tests. One test looks at the level of prostate cancer antigen 3 (PCA3) in the urine. The higher the level, the more likely that prostate cancer is present. In studies, it was used along with the PSA test. Another test looks for an abnormal gene change called TMPRSS2:ERG in prostate cells. The cells to be tested are found in urine collected after a rectal exam. This gene change is found in about half of all localized prostate cancers. It is rarely found in the cells of men without prostate cancer. Studies are under way to develop this into a test for early detection of prostate cancer.

Diagnosis

Doctors doing prostate biopsies often rely on transrectal ultrasound (TRUS), which creates black and white images of the prostate using sound waves, to know where to take samples from. But standard ultrasound may not detect some areas containing cancer.

A newer approach is to measure blood flow within the gland using a technique called color Doppler ultrasound. (Tumors often have more blood vessels around them than normal tissue.) It may make prostate biopsies more accurate by helping to ensure the right part of the gland is sampled.

An even newer technique may enhance color Doppler further. It involves first injecting the patient with a contrast agent containing microbubbles. Promising results have been reported, but more studies will be needed before its use becomes common. This test is currently only available as a part of a clinical trial.

Doctors are also studying whether MRI can be used to help guide prostate biopsies in men who previously had negative TRUS-guided biopsies but when the doctor still suspects cancer.

Staging

Staging plays a key role in deciding which treatment options a man may be eligible for. But imaging tests for prostate cancer such as CT and MRI scans can't detect all cancers, especially small areas of cancer in lymph nodes.

A newer method, called enhanced MRI, may help find lymph nodes that contain cancer. Patients first have a standard MRI. They are then injected with tiny magnetic particles and have another scan done the next day. Differences between the 2 scans point to possible cancer cells in the lymph nodes. Early results of this technique are promising, but it needs more research before it becomes widely used.

A newer type of positron-emission tomography PET scan that uses radioactive carbon acetate instead of FDG may also be helpful in detecting prostate cancer in different parts of the body, as well as helping to determine if treatment has been effective. Studies of this technique are now in progress.

Treatment

This is a very active area of research. Newer treatments are being developed, and improvements are being made among many standard prostate cancer treatment methods.

Surgery

If the nerves that control erections (which run along either side of the prostate) must be removed during the operation, a man will become impotent. Some doctors are now exploring the use of nerve grafts to replace cut nerves and restore potency. These grafts could be nerves removed from other parts of the body or something artificial. This is still considered an experimental technique, and not all doctors agree as to its usefulness. Further study is under way.

Radiation therapy

As described in the section, "Radiation therapy for prostate cancer," advances in technology are making it possible to aim radiation more precisely than in the past. Currently used methods such as conformal radiation therapy (CRT), intensity modulated radiation therapy (IMRT), and proton beam radiation allow doctors to treat only the prostate gland and avoid radiation to normal tissues as much as possible. These methods are expected to increase the effectiveness of radiation therapy while reducing the side effects. Studies are being done to find out which radiation techniques are best suited for specific groups of patients with prostate cancer.

Another approach is to place tiny implants into the prostate that send out radio waves to tell the radiation therapy machines where to aim. This lets the machine compensate for movement (like during breathing) and may allow less radiation to go to normal tissues. In theory, this could lower side effects. So far, though, no study has shown side effects to be lower with this approach.

Technology is making other forms of radiation therapy more effective as well. New computer programs allow doctors to better plan the radiation doses and approaches for both external radiation therapy and brachytherapy. Planning for brachytherapy can now even be done during the procedure (intraoperatively).

Newer treatments for early stage cancers

Researchers are looking at newer forms of treatment for early stage prostate cancer. These new treatments could be used either as the first type of treatment or after radiation therapy in cases where it was not successful.

One treatment, known as high-intensity focused ultrasound (HIFU), destroys cancer cells by heating them with highly focused ultrasonic beams. This treatment has been used more in Europe, but it is not available outside of clinical trials in the United States at this time. Studies are now under way to determine its safety and effectiveness.

Nutrition and lifestyle changes

One early study has found that in men with a rising PSA level after surgery or radiation therapy, drinking pomegranate juice seemed to slow the time it took the PSA level to double. Larger studies are now trying to confirm these results.

Some encouraging early results have also been reported with flaxseed supplements. One small study in men with early prostate cancer found that daily flaxseed seemed to slow the rate at which prostate cancer cells multiplied. More research is needed to confirm this finding.

Another study found that men who chose not to have treatment for their localized prostate cancer may be able to slow its growth with intensive lifestyle changes. The men ate a vegan diet (no meat, fish, eggs, or dairy products) and exercised frequently. They also took part in support groups and yoga. After one year the men saw, on average, a slight drop in their PSA level. It isn't known if this effect will last since the report only followed the men for 1 year. The regimen may also be hard to follow for some men.

Hormone therapy

Several newer forms of hormone therapy have been developed in recent years. Some of these may be helpful even if standard forms of hormone therapy are no longer working.

Some examples include abiraterone (Zytiga) and enzalutamide (Xtandi), which were recently approved to help treat advanced prostate cancer. They are described in the section, "Hormone therapy for prostate cancer."

Another new drug being studied, known as orteronel, works in a similar way to abiraterone. This drug may target CYP17 more precisely, which may do away with the need for taking a steroid drug such as prednisone along with treatment. Orteronel is only available in clinical trials at this time.

Chemotherapy

Studies in recent years have shown that many chemotherapy drugs can affect prostate cancer. Some, such as docetaxel (Taxotere) and cabazitaxel (Jevtana) have been shown to help men live longer. Other new chemo drugs and combinations of drugs are now being studied.

Prostate cancer vaccines

Several types of vaccines for boosting the body's immune response to prostate cancer cells are being tested in clinical trials. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, prostate cancer. One possible advantage of these types of treatments is that they seem to have very limited side effects. An example of this type of vaccine is sipuleucel-T (Provenge), which has received FDA approval.

Another prostate cancer vaccine (PROSTVAC-VF) uses a virus that has been genetically modified to contain prostate-specific antigen (PSA). The patient's immune system should respond to the virus and begin to recognize and destroy cancer cells containing PSA. Early results with this vaccine have been promising.

Several other prostate cancer vaccines are also in development.

Angiogenesis inhibitors

Growth of prostate cancer tumors depends on growth of new blood vessels (angiogenesis) to nourish the cancer cells. Looking at angiogenesis in prostate cancer specimens may help predict treatment outcomes. Cancers that stimulate many new vessels to grow are harder to treat and have a poorer outlook.

New drugs are being studied that may be useful in stopping prostate cancer growth by keeping new blood vessels from forming. Several anti-angiogenic drugs are being tested in clinical trials. One of these is thalidomide (Thalomid^®), which has been approved by the FDA to treat patients with multiple myeloma. It is being combined with chemotherapy in clinical trials to treat men with advanced prostate cancer. While promising, this drug can cause major side effects, including constipation, drowsiness, and nerve damage.

Another drug, bevacizumab (Avastin^®), is FDA-approved to treat patients with other cancers. It is now being tested in combination with hormone therapy and chemotherapy in men with advanced prostate cancer.

Preventing or treating spread of cancer to the bones

Several newer medicines may help prevent or treat prostate cancer spread to the bones.

Radium- Ra 223 dichloride (Xofigo^®, formerly called Alpharadin) is a radioactive medicine that was recently approved to treat castrate-resistant prostate cancer that has spread to the bones (but not to other organs). It is given as an injection into a vein. After traveling through the bloodstream, it settles in areas of the bones with active turnover (like those containing cancer spread). This brings small doses of radiation to prostate cancer cells in the bones. In a large study of men with prostate cancer that had spread to bone but was no longer helped by hormones, this drug helped with pain and bone problems. It also helped men live an average of a few months longer.

Radium- Ra 223 dichloride is given as a series of 6 IV injections given 4 weeks apart. Side effects are usually mild but can include nausea, vomiting, diarrhea, swelling in hands or feet, and low blood cell counts.

Cabozantinib (XL184) is a new drug that targets the MET protein, as well as having an effect on angiogenesis by targeting the VEGFR protein. In an early study, this drug was found to make bone tumors get smaller or even go away on imaging scans in many men with prostate cancer that was no longer responding to hormones. This was a very promising and unusual early finding, although it's not clear how long this might last or if the drug can help men live longer. Larger studies are now under way to try to answer these questions.

Doctors are also studying the use of radiofrequency ablation (RFA) to help control pain in men whose prostate cancer has spread to one or more areas in the bones. During RFA, the doctor uses a CT scan or ultrasound to guide a small metal probe into the area of the tumor. A high frequency current passed through the probe heats and destroys the tumor. RFA has been used for many years to treat tumors in other organs such as the liver, but its use in treating bone pain is still fairly new. Still, early results are promising.