Newest Developments in Prostate Cancer Research
Extensive research on causes, prevention, diagnosis and treatment of prostate cancer continues to be carried out in numerous medical centers around the globe.
Recent research on changes in genes related to prostate cancer helps scientists better understand the development of prostate cancer. This can enable designing the medications that target such changes. The tests performed to determine abnormal prostate cancer genes can help identify men who are at high risk and can benefit from screening programs or studies that use medications to prevent cancer.
Many gene mutations studied as factors that can potentially increase the risk of prostate cancer are transmitted with chromosomes from both parents. Some recent research has demonstrated that a certain mitochondrial DNA type inherited only from the mother can increase the risk of prostate cancer in men.
Researchers keep investigating the foods (or substances in foods) that can lower the risk of prostate cancer. Scientists have found out that some substances in tomato (lycopene) and soy (isoflavone) can help prevent prostate cancer. Trials are still being conducted to investigate potential effects of these substances more closely.
Scientists also try to develop relevant compounds that are more effective and can be used as nutritional supplements. Most of the research conducted to date suggests that a balanced diet containing other fruits and vegetables in addition to these foods is more helpful than using those substances as nutritional supplement.
A vitamin that can be critical for prevention is vitamin D. Some research has demonstrated that men with high vitamin D level have lower risk regarding more fatal types of prostate cancer. However, studies could not prove that Vitamin D offers protection against prostate cancer.
Many people assume that vitamins and other natural substances are safe; however, recent studies have shown that high doses can be harmful, especially for the supplements sold in market for prostate cancer. For instance, some studies have demonstrated that risk of advanced stage prostate cancer can increase in men who use more than 7 multivitamin pills in a week.
Another study has shown that risk of prostate cancer is higher in men whose blood level of omega-3 fatty acid is high. Fish oil capsules used by some people to improve their heart health contain high amount of omega-3 fatty acid.
Some research suggests that risk of prostate cancer and death due to prostate cancer is lower in men who take aspirin every day for a long term. Yet, additional studies are warranted to verify this finding and also reveal out that possible benefits outweigh the potential risks.
Scientists also tested certain hormone drugs, called 5 alpha reductase inhibitors, to find out a means to lower the risk of prostate cancer. Results of these studies are discussed in Prevention and Early Diagnosis of Prostate Cancer.
Doctors acknowledge that blood tests for prostate-specific antigen (PSA) are not perfect regarding early diagnosis of prostate cancer. The test misses certain cancer types, while PSA level may be high in some cases even if there is no prostate cancer. Researchers work on strategies to address this problem.
One of the approaches is to develop a test measuring total PSA level.
Another approach is to develop new tests based on other types of PSA or other tumor markers. Several novel tests appear to provide more accurate results than the PSA test:
It is not possible that these tests substitute for PSA test in near future; however, they may be helpful in certain conditions. For example, some of these tests can be useful for men with slightly high PSA level to determine whether prostate biopsy is required.
Some of these tests can be more useful to clarify whether other biopsies are necessary for men who are not diagnosed with cancer in the light of prostate biopsy. Physicians and researchers try to define the best fields of use for each one of these tests.
Physicians often rely on transrectal ultrasound (TRUS) that forms black and white image of the prostate gland using sound waves –for example- to determine the location of sampling. However, standard ultrasound may not detect some cancerous areas.
A more novel approach is to measure blood flow in the gland with a technique called color Doppler ultrasound (tumors usually have more blood vessels than the surrounding intact tissue). This may help obtaining a tissue piece from the correct part of the gland and ensure more reliable results in prostate biopsies.
And a new technique may further improve color Doppler runs. In this approach, a contrast agent, which contains micro-bubbles that help improve the ultrasound images, is injected to the patient before the scan. Although promising results have been reported, more studies are warranted before this technique is commonly used.
Physicians also investigate whether MRI can be combined with TRUS (transrectal ultrasound) or not to direct the prostate biopsies in men with negative TRUS-guided biopsies, although the physician still suspects cancer.
Determining stage (extent) of prostate cancer plays a key role in deciding the treatment options. However, imaging techniques, such as CT and MRI, used in prostate cancer cannot detect all cancer areas, particularly the small cancerous areas in lymph nodes.
A novel method, called multiparametric MRI, can help determine the extent of cancer and how aggressive can the cancer be, as these factors may affect the treatment options. This examination involves a standard MRI followed by at least one different MRI technique (diffusion weighted imaging , dynamic contrast-enhanced MRI or MR spectroscopy). Then, results of different scans are taken into consideration.
Another novel method, called enhanced MRI, may help detect the lymph nodes that contain cancer cells. First, a standard MRI is scanned. Next, small magnetic particles are injected and other scan is run on the next day. Differences between these two scans indicate the potential cancer cells in lymph nodes. The initial results of this technique are promising; however, it should be further studied before it is commonly used.
A new type of positron emission tomography (PET) that uses radioactive carbon acetate instead of labeled glucose may be helpful for determining the prostate cancer in other parts of the body and whether the treatment is working or not. This technique is also studied today.
Novel treatment methods are being developed and many standard prostate cancer treatment modalities are being improved.
Physicians constantly improve the surgical techniques for treatment of prostate cancer. The aim is to reduce the risk of surgery-related complications and side-effects while removing the entire tumor.
Technological advancements ensure delivering the beams to the target more precisely than the past. Current methods, such as conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT) and proton beam radiation therapy, help doctors protect healthy tissues from radiation as far as possible. It is expected that these methods boost the effectiveness of radiation therapy while reducing the side effects.
Technology also boosts effectiveness of other radiation therapy modalities. Novel computer software help doctors better plan the radiation doses and approaches both in external radiation therapy and in brachytherapy. Today, brachytherapy can be planned even during the procedure (intraoperatively).
Researchers are investigating novel treatments for early stage prostate cancer. These new treatments can be used as first-line treatment or in the form of radiation therapy for cases with no treatment response.
A treatment, called high-intensity focused ultrasound (HIFU), destroys the cancer cells by heating them with high intensity focused ultrasound beams. This treatment has been used for a while in some countries. Safety and effectiveness of the method are still studied.
Potential benefits of certain foods (mostly in the form of supplements) in treatment of prostate cancer have been investigated in many studies; however, most of these studies still continue. The investigated compounds include pomegranate, green tea, broccoli, turmeric, flaxseed and soy extracts.
Some of the baseline studies have demonstrated that pomegranate juice or pomegranate extract can prolong the doubling of PSA level in men whose PSA level increases after surgery or radiation therapy. Today, more comprehensive trials are conducted to investigate potential effects of pomegranate juice and extract on progression of the prostate cancer.
Some promising early outcomes have been reported for flaxseed supplements. A small-scale study conducted on men with early stage prostate cancer has demonstrated that use of flaxseed every day appears to be slowing down the division of prostate cancer cells. More studies are warranted to verify this finding.
A current study has shown that soy supplements do not decrease the risk of recurrence after prostate cancer surgeries (radical prostatectomy).
A study has demonstrated that men, who choose not to start treatment for local prostate cancer, can slow down the growth rate with intensive lifestyle changes. Men who participated in this study followed a vegan diet (without meat, fish, egg and dairy products) and did exercises at frequent intervals. Moreover, they participated to support groups and did yoga. At the end of one year, a mild decrease was noted in mean PSA levels of patients. Since the male patients were followed up only for 1 year in this study, it is not known whether this effect can last longer or not. Following this diet may prove to be difficult for some men.
Recently, several hormone therapies have been developed. Some of them may be useful even when standard hormone therapy is not beneficial anymore.
Some contain Abiraterone (Zytiga) and Enzalutamide (Xtandi) mentioned in Hormone Therapy for Prostate Cancer. Others are in test phase.
5-alpha reductase inhibitors, such as Finasteride (Proscar) and Dutasteride (Avodart), are medications that prevent transformation of testosterone to dihydrotestosterone (DHT). These medications are being tested either to support active surveillance or treat prostate cancer in case of elevated PSA following prostatectomy.
Recent studies show that many chemotherapy drugs have positive effects on prostate cancer. For example, it is demonstrated that Docetaxel (Taxotere) and Cabazitaxel (Jevtana) help prolong survival in men.
Recent comprehensive trials show that the chemotherapy drug (Docetaxel) administered at early stage helps prolong survival in men with metastatic prostate cancer. These outcomes are encouraging, but these studies were conducted before new hormone therapies (Abiraterone and Enzalutamide) were introduced into clinical use. Accordingly, it is not clear whether these results are same today.
Other novel chemotherapy drugs and their combinations are also being tested.
The purpose of immunotherapy is to strengthen the immune system and help it fight or kill cancer cells.
Unlike mumps and measles vaccine, prostate cancer vaccines are designed to treat prostate cancer rather than prevention. One of the advantages is very few side effects. Sipuleucel-T (Provenge) is one of these vaccines approved by FDA (specified in Vaccine Therapy in Prostate Cancer).
Some other vaccines that are intended to treat prostate cancer are being tested in clinical trials.
One is PROSTVAC; this vaccine uses a virus that is genetically modified to carry prostate-specific antigen. The immune system responds to the virus and begins identifying and killing PSA-containing cancer cells. Early outcomes of this vaccine are promising and preparations are being made for a more comprehensive study.
One important feature of the immune system is the capability of not attacking healthy cells in the body. For this purpose, the immune system uses “checkpoint molecules”, which activate (or deactivate) the immune cells, to initiate an immune response. Sometimes, cancer cells use these checkpoints to escape from the immune system. However, novel medications that target these checkpoints have yielded promising outcomes in cancer treatment.
For example, these new medications, such as Pembrolizumab (Keytruda) and Nivolumab (Opdivo), target the immune checkpoint protein (PD-1). It is indicated that such medications shrink a substantial part of tumors in some types of cancer. Studies are still conducted that evaluate effects of these medications on prostate cancer.
Another one is Ipilimumab (Yervoy) that target the CTLA-4, a checkpoint protein found in certain immune cells. This medication is used to treat some other types of cancer and it is still in the test phase for advanced prostate cancer.
Combination of checkpoint inhibitors and prostate cancer vaccines may be a promising approach in the future. This may improve the immune response and ensure that the vaccine provides a better effect.
New medications have been developed that target a certain part or peripheral areas of cancer cells. Each targeted therapy has unique features, but all change the growth, proliferation, division, regeneration of cancer cells and the interaction between cancer cells and other cells.
For example, angiogenesis inhibitors inhibit development of new blood vessels that tumors require for growth. Today, a few angiogenesis inhibitors have been tested in clinical trials.
Doctors use radiofrequency ablation (RFA) for pain management in men with prostate cancer that has spread to bones or multiple body parts. During RFA, the doctor uses CT or Ultrasound to insert a small metallic probe into the tumor area. High-frequency waves pass through the probe and heat up and destroy the tumor. RFA has been applied for a long time to treat tumors in other organs, such as liver, but doctors recently started using this method for bone pain management as well. Nevertheless, the baseline outcomes look promising.
