Category: Treatment Information
A Longer-Term Study of Treatment Side Effects of Early-Stage 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.
Screening and Treatment News Items from the Prostate Cancer Research Institute (PCRI) Highlights
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.
Phase 2 or 3 Clinical Trials for Men with Hormone-Resistant, Metastatic Prostate Cancer.
The Prostate Cancer Research Institute (PCRI) recently published the particulars for four clinical trials (Phases 2 and 3) for men with metastatic, castrate-resistant (i.e. PSA progressing with reduced testosterone) prostate cancer. The first Phase 2 trial involves treatment with Enzalutamide (Xtandi or MDV 3100) administered with or without Prostvac. For a brief summary of these therapeutic agents and how they work, see the January 3rd, 2012 website blog. The second is a trial involving the co-administration of Indoximod and Provenge (Sipuleucel). Indoximod is an agent that targets mechanisms by which tumors evade the immune system. The third trial (termed PROMOTE) is studying the gene expression patterns of castrate-resistant patients currently receiving treatment with Zytiga (abiraterone acetate). The fourth is a Phase 3 trial of Prostvac with or without GM-CSF (granulocyte macrophage colony stimulating factor), a protein that functions as a white blood cell growth factor. For additional information, see the links in this blog. For overall clinical trials information, see (1) http://www.clinicaltrials.gov and specifically search for prostate cancer trials; (2) http://www.cancer.gov, a site from the National Cancer Institute, National Institutes of Health; or, (3) for trials being conducted solely in the state of Florida, see http://www.Flcancer.com.
Targeted Radiotherapy for Men with Micro-Metastatic, Advanced Prostate Cancer. Phase II Clinical Trial Information.
Scientists at Weill Cornell Medical College in New York have attached a chemical tag (the isotope lutetium-177) that emits small amounts of radiation onto a monoclonal antibody (J591) that targets prostate cancer cells in bone, soft tissues and circulating blood that carry the protein antigen, prostate-specific membrane antigen (PSMA). Treatment with 177Lu-J591 may be optimally suited to patients with micro-metastatic disease. The developers of this therapy postulate that such treatment in men who have small volume disease not seen on bone scans could even result in a cure for some patients. They specifically refer to men who have had surgery and/or radiation at their primary prostate tumor site who are then experiencing rising PSA levels (biochemical failure) but their bone and CT scans remain negative for metastatic cancer. Results of a Phase II clinical trial of 177Lu-J591 in men who had failed hormonal therapy are summarized in a Jan. 31st, 2014 article from the Prostate Cancer Foundation (PCF). A subsequent Phase II clinical trial at Weill Cornell Medical College and twelve other centers is underway to determine if 177Lu-J591 can delay or prevent overt metastatic disease in men with rising PSA levels after primary treatment and early hormonal therapy but in whom bone and CT scans remain negative. The PSMA antigen is also expressed in other tumors such as liver, breast and kidney; hence this targeted radiotherapy could possibly be used in tumors other than prostate cancer. For further details, see the linked PCF article.
Coffee, Caffeine, PSA Velocity and Hormonal Therapy.
As we have come to expect, the Johns Hopkins Medicine Health Alerts always contain useful information for prostate cancer patients. For example, the January 19th, 2014 issue contained a primer describing the basic concepts and rationale of hormonal therapy. The February 9th edition reported three published studies which link coffee drinking and caffeine to a risk reduction for several types of cancer including aggressive prostate cancer, and its recurrence and progression. Thirdly, the February 16th issue described a study that concluded that PSA velocity (the rate of PSA change over time) “accurately predicted which men would develop prostate cancer and was significantly more accurate than a single PSA measurement in predicting which men would develop aggressive disease.”
Radiation Therapy Meeting Highlights; IMRT Review.
PCRI Insights is published monthly by the Prostate Cancer Research Institute (PCRI) and is must-reading for men with prostate cancer. The November 2013 issue featured a summary of several pertinent abstracts of presentations given at a recent annual meeting of radiation therapists. One abstract presented cure rates achieved with intensity modulated radiation therapy (IMRT) combined with a boost from seed implants. IMRT is a refinement over existing radiotherapy modalities providing for a higher dose of radiation to the tumor while exposing surrounding tissue to less radiation. An excellent review of IMRT has been published in Cancer News. Another study compared the preservation of potency in young men treated with radiation as compared to surgery. A third study and commentary addressed the issue of when radiation therapy should be commenced after PSA relapse. Other abstracts addressed the issue of the timing of the use of hormone blockade accompanying radiation therapy. The final study examined the effect of the rate of PSA doubling on survival rates and times in relapsed prostate cancer patients originally treated with IMRT. Finally, it should be noted that the studies presented here focused on radiation therapy. A man considering treatment for prostate cancer is urged to consider additional modalities before deciding on a specific, personal course of treatment.
Highlights of 2013-continued. Inflammation,Diet and Prostate Cancer; FDA Approvalof Xofigo; and, a Guide to Genes and Prostate Cancer.
Chronic inflammation is suspected to play a role in numerous diseases such as heart disease, Alzheimer’s, arthritis and cancer. If this is the case, then could reducing chronic inflammation by dietary means reduce the incidence of prostate cancer for example? This question is being studied extensively and is the focus of an article in the December 20th issue of the Prostate Cancer Foundation NewsPulse. Researchers at Johns Hopkins are studying prostate cells as they transition from normal to pre-cancerous and finally to cancerous. They speculate that inflammation may be an early factor inducing healthy prostate epithelial cells into the cancerous cycle. Since obesity is already linked to an increase risk of death from prostate cancer, could an anti-inflammatory diet have an effect on the incidence and severity of prostate cancer? A diet similar to the Mediterranean diet may be of help and is described in the NewsPulse article. Helpful foods include whole grains, healthy fats (as opposed to animal or trans fats), fruits and vegetables, spices such as ginger, garlic, cinnamon, and curcumin, green or oolong tea, nuts such as walnuts, oil-based salad dressing, omega-3 fatty acids derived from vegetable oils or flaxseed (as opposed to fish such as salmon), and others in the PCF article. While the anti-inflammatory diet includes many foods that may have health benefits for men with prostate cancer, further research is needed into specific components and the dietary patterns as a whole in order to assess how this diet may affect men with prostate cancer. As always, be advised to consult with your medical professional.
A second major story in this year-end issue of the PCF NewsPulse cites the FDA approval in spring, 2013 of Xofigo, radium-223-chloride, also known as alpharadin for the treatment of men with advanced metastatic prostate cancer. Xofigo extends survival, improves quality of life, requires less opioid medication for bone pain and its resulting side effects, and reduces complications such as spinal cord compression and bone fractures which result from bone tumors. Additional information is available in the accompanying article. This website has also posted information on this agent in previous blogs dated November 5th, 2011, January 3rd, 2012, April 28th, 2012 and June 3rd, 2013.
The third article from NewsPulse provides an excellent summary of a number genes and their proposed involvement in prostate cancer. Specific genes include HOXB13 (associated with hereditary prostate cancer), the female breast cancer susceptibility genes BRCA1 and BRCA2, the fused genes TMPRSS2-ERG and others. This review would be useful for physicians as well as laymen.
Targeted Delivery of Cancer Drugs Such as Docetaxel (Taxotere).
An August 11th, 2013 blog (below) on this website described how a chemotherapeutic drug such as docetaxel (taxotere) used in the treatment of advanced prostate cancer could be administered more effectively and with less side effects. Taxotere is a variant of an anti-cancer drug (taxol) originally isolated from yew plants.
Nanoparticles are chemical species which can serve as a targeted delivery system for drugs, proteins and other therapeutics. The drug to be delivered is contained within the nanoparticle whose surface is then coated with targeting moieties such as antibodies. The overall result is the delivery of a specific drug directly to the cancer cells thereby allowing for higher localized doses and minimized systemic side effects. This type of delivery system for docetaxel (taxotere) is given as an example in a video and accompanying article from the July 31st, 2013 issue of the Prostate Cancer Foundation NewsPulse. Docetaxel is a chemotherapy used in metastatic, hormone-refractory prostate cancer patients. While it is efficacious, it also can produce serious side effects. It is also limited in the amount of drug which can be administered intravenously. Therefore, nanoparticle delivery can be much more efficacious.
Now in the October 31st, 2013 issue of the Prostate Cancer Foundation (PCF) NewsPulse, the nanoparticle delivery system for docetaxel (taxotere) which specifically targets cancer cells is described and illustrated in more detail. This technology allows higher doses to be administered and reach the tumor with fewer side effects for the patient. This targeted taxotere delivery system (called BIND-014) is being developed by BIND Therapeutics and is currently in Phase II clinical trials in men with treatment-resistant, metastatic prostate cancer and non-small cell lung cancer. BIND-014 specifically targets an antigen called prostate-specific membrane antigen (PSMA) found on the membranes of prostate cancer cells as well as on blood vessels within tumors that feed cancer cells. Details of the current Phase II clinical trial of BIND-014 are discussed in the NewsPulse article.
Neuroendocrine Prostate Cancer; a Lethal Result of Resistance to Hormone Therapy.
