A “Buffet” of Prostate Cancer News Items; Hormonal and Radiation Therapy, Younger Patients and the Effects of Statin Drugs.bjgabrielsen : May 19, 2014 1:48 am : 2014, General Patient Information, Treatment Information
1) Intermittent Hormonal Therapy: Prostate cancer is often kept “under control” by depriving the cancer cells of their “fuel”, namely androgens such as testosterone or dihydrotestosterone. Androgen deprivation (hormonal) therapy (ADT) is often applied on an intermittent basis the goal of which is to minimize potentially harmful side effects. The May 11th edition of the Johns Hopkins Prostate Disorders Health Alerts contained an excellent overview of intermittent androgen suppression.
2) Why Androgen Deprivation Enhances Radiation Therapy: It has been known since 2011 that adding a short course of androgen deprivation therapy (ADT) to radiation therapy in prostate cancer patients increased their chances for survival. Recent research indicates that the rationale for this combination treatment lies in the fact that ADT retards the ability of cancer cells to repair DNA damage caused by the radiation therapy thus leading to their programmed cell death or apoptosis. One such DNA repair enzyme is called DNAPK which may be a good target for antitumor drug development. Inhibitors of a similar single-strand DNA repair enzyme, PARP1 [(polyADP-ribose) polymerase], are currently being evaluated in Phase III clinical trials involving breast and ovarian cancers. (PARP1 inhibitors seem to have a beneficial effect on women with a specific BRCA breast cancer genetic mutation.) The relationship between the androgen receptor (AR) and DNA repair proteins such as DNAPK is also summarized in the March 31st issue of the Prostate Cancer Foundation (PCF) NewsPulse.
3) A Study Comparing “Watchful Waiting” versus Surgery in Younger Prostate Cancer Patients: A joint Swedish – Harvard life expectancy study of 700 men with early prostate cancer and published in the March 6th New England Journal of Medicine concluded that surgery (radical prostatectomy) may “trump” watchful waiting in younger men diagnosed with prostate cancer. A summary of this study and comments by other researchers was published in the March 31st issue of the Prostate Cancer Foundation (PCF) NewsPulse.
4) The Effects of Statin Drugs On Prostate Cancer: The March 31st PCF NewsPulse also contained a review of various studies related to the effects of cholesterol-lowering statin drugs on prostate cancer. Researchers conclude that statins do not have an effect on the incidence of prostate cancer however prolonged use may lower the risk of advanced disease and death. No protective effects from statins have been observed and there does not seem to be any association between statin use and early incidence of prostate cancer. Current research is focused on where statins may play a role in the overall prostate cancer cycle.
Four Clinical Trials Involving Focal Therapy for Prostate Cancer Patients Who are Low-Risk or Under Active Surveillance.bjgabrielsen : May 9, 2014 5:09 am : 2014, Treatment Information
The Prostate Cancer Research Institute (PCRI) recently published details of four (4) clinical trials which are recruiting low-risk prostate cancer patients or those currently under active surveillance. Low-risk determination is based upon PSA, Gleason score, and clinical stage. The treatments offered are referred to as “focal therapy” wherein a portion of the prostate is being treated instead of the entire gland. The clinical trials include brachytherapy (radioactive seeds), laser (interstitial thermal therapy) and high intensity focused ultrasound (HIFU). Details concerning location, eligibility criteria, and contact information are provided in the PCRI link. Clinical trial locations include Memorial Sloan Kettering in New York, University of Chicago, Mayo Clinic, City of Hope, and Desert Medical Imaging (California). Three of these studies involve MRI-guided therapies.
I started to write a post last night dealing with some very interesting prostate cancer clinical trials. Upon logging on to my website, I discovered to my dismay that all the previous pictures that I had posted were missing and only one remained, that one appearing on every section. I verified that no written content had been altered hence hackers were not involved. My personal knowledge of website maintenance is sorely limited.
My passion, mission and ministry is to communicate spiritual (Christian) and medical content to you, the readers and especially to those who, like me, face prostate cancer. I personally maintain this site financially but I have been blessed with two colleagues who are website experts and who are compensated to maintain this site. The problem with the missing pictures is “under review” as I write this. The website problems put a damper over my morning but as so often happens, God had a specific word for me as I read my morning devotionals. The first was the May 8th devotional in Our Daily Bread.
The Bible reference was from 2 Corinthians 4:1-6. Verse one reads as follows. “Therefore, since we have this ministry, as we have received mercy, we do NOT lose heart.” This was just what I needed to hear!!!! As Christians, we are not immune to life’s problems. The Lord just told me in His word, that I am not to lose heart. God has the solutions, and when we submit our lives and all its component parts to Christ’s lordship, His methods always lead to the best results when all is said and done. I humbly ask for your prayers that our “picture” problem be solved and that this website can continue to be of service and remain functional.
It took about 3-4 hours of work to solve the problem with the pictures. So whatever our situation, may we not waver in our faith and trust in the Lord. (If you are not sure of your relationship with God, see the linked website section.) As the most loving Father, God has our best interests at heart and let us remember to trust Him in whatever circumstance and location wherein He has planted us. May people with whom we have contact see God and Jesus through our actions and attitudes. In the words of an old song, “you may be the only Bible some will ever read.” So “let’s bloom where we are planted.”
A recent clinical trial study funded by the National Institutes of Health (NIH) yielded some promising results for men with prostate cancer which had metastasized to liver, lungs, bones or adrenal glands. The study examined the effects of combining hormonal therapy with chemotherapy and so far, this combination had extended the three-year survival rates from 52.5 percent to 69 percent. Men with hormone-sensitive metastatic prostate cancer are typically treated first with androgen (hormone) deprivation therapy to slow the tumor growth. When researchers added the chemotherapy drug docetaxel (taxotere) at the start of the hormone therapy regimen, they noted significant improvement in survival among patients with the most advanced prostate cancer. Both drugs have been approved by the Food and Drug Administration (FDA) hence are available for immediate use in patients with a high extent of metastatic prostate cancer. Studies of the combination therapy are on-going to determine its effectiveness in treating less extensive metastatic prostate cancer.
If you or a loved one is considering treatment for early-stage prostate cancer, you may wonder about long-term side effects. Here are the latest research findings.
Until recently, most studies of side effects experienced by patients treated for localized prostate cancer have only lasted a few years. Fortunately, that has begun to change. The longest follow-up to date comes from a 2013 study reported in The New England Journal of Medicine.
Researchers identified 1,655 men with localized prostate cancer who were treated with surgery or radiation in the mid-1990s and were age 55 to 74 at the time of treatment. Over a 15-year period, the researchers periodically asked the men if they were experiencing erectile dysfunction, urinary incontinence or bowel urgency.
The findings. After five years, men who had surgery were significantly more likely to have erectile dysfunction and urinary incontinence, while men who received radiation therapy had higher rates of bowel urgency. But after 15 years, rates of these concerns were similar in both groups, and most of the men, regardless of treatment, had developed erectile dysfunction. Some men underwent additional treatments, which may have increased their risk of developing side effects, but these problems also become more common in all men with the passage of time.
Because men usually live for many years after therapy for localized prostate cancer, it’s important to keep the short- and the long-term pictures in mind when making treatment decisions. These new findings shed important light on the latter.
The above appeared in the April 20th issue of the Johns Hopkins Health Alerts. I strongly recommend that the readers of this website subscribe electronically to this valuable service from Johns Hopkins Urology. See the attached link. A significant lesson I and many others have learned from our prostate cancer experiences is that no matter what therapeutic route is chosen, a man is anatomically “never quite the same”. The goal is to minimize all potential side effects by availing one-self of the best physicians and resources available.
In the area of prostate cancer diagnoses, the ultimate goal is to find methods which would reveal whether a man has prostate cancer or is cancer-free, and if cancer is detected, is it aggressive requiring treatment or slow-growing requiring only monitoring. Many of these tests utilize biomarkers, substances like prostate-specific antigen (PSA) measured in a body fluid. While much data is available on the use of PSA, published studies on newer tests is very limited. Such tests can also be marketed without proof of benefit and may contain unsubstantiated claims. Given these limitations, here are some tests that are commercially available. Your personal physician should be consulted first and foremost. Costs and insurance coverages vary greatly. Insurance carriers and test manufacturers should be contacted for further information and possible assistance.
In addition to PSA, two tests that could help to decide whether a biopsy is necessary include the Prostate Health Index (phi test) and the 4Kscore. The phi test measures blood levels of PSA, free PSA and a precursor of PSA called pro-PSA or p2PSA. The phi test combines all three measurements mathematically to better determine whether prostate cancer is present. The phi test results (scaled from zero to 55 and above) reflect the probability that a biopsy will detect cancer. Research suggests that pro-PSA levels are a better indicator of prostate cancer than total or free PSA levels. Men with elevated pro-PSA levels are at risk for a more aggressive form of cancer. The test is indicated for men 50 years and older who have negative digital rectal exams and PSA levels of 4-10 ng/mL. For additional information on the phi test and its availability, see the following link to Beckman Coulter Diagnostics. The 4Kscore is a blood test which measures levels of three variants of PSA (total, free and intact PSA) plus an enzyme called human kallikrein 2 (hK2) which is elevated in men with prostate cancer and may promote its growth and spread. The 4Kscore is slated to be released in the United States in 2014.
Other tests are available to help determine whether a repeat biopsy is necessary as some initial prostate biopsies are inconclusive or negative in high-risk men. Progensa is a urine test that detects the presence of a gene called prostate cancer antigen 3 (PCA3). This gene is over-expressed (more active) in 95% of men with prostate cancer but not in men with healthy or enlarged prostates. Progensa can be used in men over 50 who have had one or more negative biopsies but who may be deemed candidates for prostate cancer nonetheless. This test has been discussed on this website in blogs dated 3/26/2012, 7/16/2013, 10/8/2013 and 12/31/2013. ConfirmMDx is a test that analyzes the DNA methylation status of a man’s biopsied prostate tissue. DNA methylation is a biochemical process that “tags” specific parts of DNA (the building blocks of genes). The result of this process is that the activity of tumor suppressor genes is decreased or turned “off'”, thus facilitating cancer development. The Prostate Core Mitomic Test analyzes a man’s biopsied tissue looking for damage to mitochondrial DNA caused by cellular changes associated with prostate cancer. A negative test indicates a low risk for undiagnosed prostate cancer and repeat biopsies can be deferred.
If prostate cancer is detected, the big question is whether treatment is immediately required or could active surveillance be invoked. Is the tumor low-risk or aggressive? Gleason score and other information are currently used to provide these answers however several tests may also help. Prolaris is a test that uses a sample of biopsied tumor tissue to measure how rapidly cells are dividing. Prolaris scores range from -1.3 to + 4.7, with higher scores indicating a greater risk of dying from prostate cancer. Prolaris may also help to determine the risk of recurrence after a prostatectomy and to determine whether a man would benefit from additional therapies such radiation or hormone therapy. The Prolaris test has been described on this website in the April 12th, 2014 blog. The test called ProstaVysion analyzes biopsied tissue for the presence of two biomarkers. One is TMPRSS2:ERG, a fusion of two genes associated with the presence of prostate cancer. The other is PTEN, a gene that normally help suppress certain forms of cancer and is missing in 60% of men with metastatic prostate cancer. These two markers help provide a molecular analysis of prostate cancer aggressiveness and the patient’s long term prognosis. These genetic markers were also discussed in previous website blogs dated July 16, 2013, October 8th, 2013, December 31st, 2013 and January 4th, 2014. Thirdly, Oncotype DX examines the interactions between 17 genes in a biopsy sample to predict whether a tumor is likely to be aggressive. The resulting Genomic Prostate Score ranges from 0 to 100; a lower score suggests that the tumor is less likely to grow and spread while a higher score suggests a poorer prognosis and the need for immediate treatment. This test was also described previously in posts dated June 21, 2013 and January 10th, 2014. Finally, the NADiA ProsVue blood test measures the rate of tiny changes in PSA levels over time which can suggest the level of risk for recurrence for several years following a prostatectomy.
More specific information can be found in an article written by Dr. H. Ballentine Carter, Director of Adult Urology at Johns Hopkins in the May, 2014 issue of the Johns Hopkins Medicine Health After 50. One can subscribe to receive this periodical from Johns Hopkins for a fee.
The Prostate Cancer Research Institute publishes a monthly periodical called “Insights”. At the end of 2013, they also updated their user-friendly and searchable website, http://www.pcri.org. The February 2014 issue of Insights contained considerable information which I will briefly summarize. I encourage you to see the articles in their entirety.
First, Dr. John Davis from MD Anderson Cancer Center describes the “Prolaris Test for Prostate Cancer” which serves as an introduction to this novel genomic test and its role in improving clinical decisions about treating prostate cancer. Prolaris is a test performed on biopsy tissue that looks at the average expression of 31 Cell Cycle Progression (CCP) Genes, which are involved in telling a cell to divide in two. Such a test result can be grouped with other factors to help determine the potential prostate cancer aggressiveness or lack thereof. The test can be helpful in men who are interested in active surveillance but may not have low-grade, low-volume disease. It can help define the risk of cancer-related mortality if left untreated. The test is expensive (around $3400) and insurance coverage can vary.
Secondly, an article by Dr. Mark Scholz summarizes presentation highlights from a recent Prostate Cancer Foundation retreat. One presentation described the discovery of a new gene product called SCHLAP-1 that can help predict the likelihood of future metastases. SCHLAP-1 may have the same predictive power as a Gleason score in distinguishing low-grade from high-grade disease. Another presentation discussed the role of PSA decline as a measure of treatment effectiveness. PSA can be notably inaccurate as demonstrated with Provenge and Xofigo as neither causes a consistent decline in PSA though both have been shown to improve survival. Dr. Howard Scher of Sloan-Kettering described studies that rely on measuring a decline in circulating tumor cells (CTC) in response to therapy as an accurate method for early prediction of long-term survival. Dr. Scher combines CTC levels with measurement of an enzyme called lactate dehydrogenase (LDH) to differentiate patients into low, intermediate or high risk categories. The system has been tested and validated to predict survival and could be used by the FDA for evaluating new drugs according to Dr. Scher. Dr. Victor Velculescu from Johns Hopkins presented his work which suggests that the presence or absence of microscopic residual disease (micro-metastases) could be detected with new genetic tests called genomic analysis. If a test could confirm that a patient was free of metastases, then long-term hormonal treatment might be unnecessary.
An effect called the Abscopal Effect states that radiation may actually stimulate one’s immune system according to Dr. Mark Scholz. Presently, little is known about how anti-cancer therapies such as radiation interact with immunotherapy in a clinical setting. Phoenix, AZ – based 21st Century Oncology is beginning a clinical trial designed to determine if radiation-induced tumor death augments the anti-tumor responses from Provenge. Patients treated with a combination of spot radiation and Provenge will have their tumor responses tracked with C11-acetate PET scans. See the article for details.
In an article named “A New Approach to Prostate Cancer Screening”, the authors suggest that “rather than doing an immediate biopsy, doctors should consider prostate imaging with multi-parametric MRI or Color Doppler Ultrasound. In experienced hands with state-of-the-art equipment, high grade cancer can be ruled out with 95 to 98% accuracy. And when imaging detects a high-grade lesion, a targeted biopsy directed specifically at the area of abnormality can be performed. If the scans show that no high-grade disease is present, the patient can forgo biopsy and simply monitor the situation with further PSA testing and, if necessary, consider additional imaging in six to twelve months.” The same issue contains an article called “What’s New in Prostate Cancer” by Dr. Stanley Brosman. He discusses the use of multi-parametric-MRI (mp-MRI) to see abnormalities suspicious for prostate cancer. mp-MRI does tend to miss cancers that are low-grade which may be a good thing. In experienced hands, the ability to detect Gleason score 7 or 8 tumors was 98% accurate and the ability to predict the absence of aggressive tumors was 91%. This technique also allows for a more targeted approach to doing a needle biopsy. The mp-MRI is also very useful for following prostate cancer patients who are on Active Surveillance. A drawback is that a specific type of MRI, namely a 3-Tesla MRI, is needed in the hands of a highly trained radiologist. The test is also currently expensive and may not be covered by all types of insurance.
Finally, medications to treat osteoporosis in men receiving hormone therapy have been widely used for years. It has now been learned that men who have bone metastases can have stabilization and regression of the tumor with the use of these agents. Denosumab (Prolia) and XGEVA are being used with good results. It was reported that the use of Denosumab (Prolia) may be a preventive agent and delay the onset of bone metastases in high-risk patients.