Category: General Patient Information

November News Items: 1) Watchful-Waiting; 2) New drug TAK-700; 3) Use of Cryotherapy After Failure of Radiation or Brachytherapy.

1) The November 16th, 2011 issue of the Newsletter from Zero-The Project to End Prostate Cancer, published an interesting article from the New York Times entitled “A  Watch-and-Wait Prostate Cancer Treatment.”  The article focused on the PSA screening and subsequent actions that a man over the age of 70 can take to keep his prostate cancer from developing further and becoming problematic. Subjects such as cryosurgery, diet and nutrition, screenings and biopsies are discussed along with helpful advice from noted urologists.

2) The drug, TAK-700 (Ortoronel) and Phase 3 clinical trials have been described in a blog published on this website on June 3rd, 2011. TAK-700 is an oral, non-steroidal, androgen (e.g. testosterone) synthesis inhibitor.  It is being developed by the Takeda Oncology Company affiliated with Millennium. They are sponsoring safety and efficacy clinical trials in men with metastatic prostate cancer who have not had previous chemotherapy or who have had chemotherapy more than two years earlier for early-stage prostate cancer (elm pc004) or metastatic cancer who have received chemotherapy (elm pc005). The trials are evaluating the safety and efficacy of TAK-700 when combined with prednisone as compared with prednisone alone.  End points of the study are delay in disease progression and increased survival times.  For details, see their website at http://elmpctrials.com/eligibilityAssessment.html?

3) The November 16th issue of Johns Hopkins Prostate Disorders Health Alerts (link) discusses the attractive option of using cryotherapy as a salvage procedure following failure of external beam radiation and/or brachytherapy to eradicate all the prostate cancer. Cryotherapy could minimize potential damage to the bladder and/or rectum which could occur if surgery or additional radiation therapy were used. See the full article for details.

b) Earliest Known Cases of Prostate Cancer.

North rim of Grand Canyon, Arizona- bj gabrielsen

In an article published in the International Journal of Paleopathology, a research team in Portugal has recently diagnosed the oldest known case of prostate cancer in ancient Egypt and the second oldest documented case in the world. The earliest diagnosis came from a 2,700 year-old skeleton of a Scythian king in Russia. The tumors were detected by performing high-resolution computerized tomography (CT) scans on three Egyptian mummies in which small, 1-2 mm diameter tumors were detected in the pelvis, lumbar spine and upper arm and leg bones. While it has been thought that exposure to carcinogens during the industrial age led to a general increase in cancers, this disease could have been prevalent in ancient peoples as well. This information was adapted from ScienceNOW, an on-line daily news service of the journal Science.

URGENT ACTION NEEDED! Government Proposes Elimination of Prostate Cancer Testing. Does PSA Screening for Prostate Cancer Save Lives?

The United States Preventive Services Task Force (USPSTF), an independent panel appointed by the Federal cabinet-level Department of Health and Human Services (DHHS), is preparing a recommendation which would eliminate prostate cancer testing (PSA) for all men. The rationale cited by the government panel is that there is moderate or high certainty that PSA testing has no net benefit or that its harms outweigh its benefits. (It should be noted that the panel did not include a urologist nor a medical oncologist.) The basic question involved in this recommendation is whether or not routine PSA testing saves men’s lives. Prostate cancer patients, survivors and advocates are being urged to voice their opinion about this recommendation to their Senators and members of Congress. Additionally, the USPSTF is accepting public comments on the new recommendations for the next four weeks. Links to communicate your opinions can be found in the October 7th and October 12th ZeroHour Newsletter from Zero-the Project to End Prostate Cancer.

Two major conflicting medical studies, one American and the other a European study, are being cited as evidence for/against this recommendation. These studies and their conclusions have been summarized by Dr. Patrick Walsh from the James Buchanan Brady Urological Institute – Johns Hopkins University on its website.  (It should be noted that this institute at Johns Hopkins has been named the #1 choice for urology for the last 21 years consecutively by the annual survey in U.S. News and World Report. Dr. Walsh pioneered the development of the surgical nerve-sparing techniques whereby nerves controlling erections and urination are spared from damage during radical prostatectomies.) The European study was carried out in seven European countries involving 162,000 men who were randomized to PSA screening every four years versus no screening. After fourteen years of follow-up, “there was a 20% decrease in deaths from prostate cancer in the group of men assigned to screening.” Further examination of the data leads to a conclusion that the decrease in prostate cancer deaths could be as high as 27%.  According to Dr. Walsh, “this reduction in death from prostate cancer is similar to the 30% reduction in mortality from breast cancer in women who undergo mammography and the 33% reduction in prostate cancer mortality that occurred in the United States between 1994 and 2003 following the introduction of PSA screening. Thus, the results from the European study support other findings and unequivocally demonstrate that PSA testing can save lives.” The second trial was carried out in the United States and was half the size of the European trial. “It compared screening with PSA every year for six years with no screening thereafter versus no planned screening. It showed no improvement in prostate cancer mortality at 7 years.” The reader is encouraged to review Dr. Walsh’s comments on these trials at the Brady Urological Institute website.  He concludes that “if you are a healthy man age 55-69 who does not want to die from prostate cancer, the European trial provides conclusive evidence that PSA testing can save your life.”

What could occur if PSA screening was less accessible? What would be the options for a middle-aged man? A physician and close friend commented as follows. There are no specific symptoms whatsoever of the early stages of prostate cancer. The signs of early prostate cancer are indistinguishable from the signs of benign prostatic enlargement that commonly occurs as we age–namely, a weak or intermittent urinary stream, hesitancy (difficulty starting the flow of urine), straining, dribbling, having to get up at night to urinate, and the need to strain during urination.  More serious signs–that increase the odds of a cancer being present–include blood in the urine and bone pain especially in the pelvis, ribs, or back.  Any of the symptoms mentioned above in a man over 40 years old should prompt a visit to a physician. If cancer were present, blood in the urine and bone pain would seem to indicate the disease had advanced considerably by this point if more routine PSA screening had not been available.

As with any treatment, there are both benefits and risks. In the pre-PSA era, approximately 80% of patients who were diagnosed with prostate cancer, were already in advanced stages of the disease with metastatic cancer. Today, the number of patients who are diagnosed with metastatic disease at the time of initial diagnosis is around 20%. In the past 15 years, the prostate cancer death rate has been reduced from 42,000 annually to 33,000. On the other hand, according to the Prostate Cancer Foundation’s NewsPulse, PSA screening leads to biopsies wherein less than half of the patients who are biopsied each year are subsequently diagnosed with cancer.  In addition, recent studies show that approximately 7% of men over 65 who have prostate biopsies are hospitalized within 30 days of the procedure, primarily due to infections according to the October 4th issue of the National Cancer Institute Bulletin.

Treating men over 70 aggressively for prostate cancer when instead their cancers might never become life-threatening is a practice that needs to be reduced. Instead, concentrating treatment on younger prostate cancer patients should be encouraged.

Personally, at the age of 54, my own cancer was discovered by a biopsy which was dictated by a moderately-consistent PSA of 4-5 ng/ml. I underwent a radical prostatectomy in 1995 at Johns Hopkins which resulted in virtually none of the side effects such as incontinence and impotence. This is indicative of the Johns Hopkins surgical nerve-sparing skills. (This website tells my entire story and lessons learned.)

There are more positive recommendations that could be made in the case of prostate cancer screening. PSA screening in patients should be more selectively targeted thus reducing over-testing and risks from over-treatment. Annual PSA screening may be better utilized as a baseline test and a series of tests over time to determine the rate of change of the PSA values with time (PSA velocity). Another useful test is prostate density, which refers to the PSA divided by the estimated weight of the prostate. A PSA of 5 ng/ml in a small prostate is more likely to indicate a cancer than a PSA of 8 ng/ml in a very large prostate. Also, through joint public-private research partnerships, government scientists such as those at the National Cancer Institute (NCI) of the National Institutes of Health (NIH) could focus stronger efforts on better early detection tests of lethal prostate cancers.  Above all, validated biomarkers that are prevalent in most prostate cancers and could be detectible in urine or blood tests are sorely needed in order to detect and determine the aggressiveness of prostate cancers.  For example, the DNA markers TMPRSS2:ERG gene fusion and PCA3 (prostate cancer antigen DNA) are expressed at high levels in 95 percent of prostate cancers.  The gene fusion TMPRSS2:ERG occurs in 50 percent of prostate cancer patients. This two-gene DNA urine test is ultra-specific to prostate cancer and prostate cancer only.

Thank you for reading this most urgent blog. Please express your opinions on PSA screening to your senators and congressional representatives as well as to the USPSTF government panel.

For Those Contemplating Radiation Therapy

Very few, if any, treatments are without side effects. Whatever route a person takes to treat prostate cancer, one is usually “never quite the same again.” Radiation therapy is no exception. Urinary tract and bowel effects can be encountered. You do not want to have to constantly focus on the nearest bathroom facility. Therefore, before undergoing radiation therapy, one would be wise to investigate the types of radiation technologies offered by various facilities. Carefully consider all potential side effects, success rates as well as comments from former patients as well as the levels of expertise of their personnel. Driving along highways in Florida, one can see numerous billboard advertisements all promoting “cutting edge” radiation facilities. Be a “wise consumer”; it’s your body and the side effects can last a long time. A good source to begin the learning process is from Johns Hopkins Hospital in Baltimore, MD, the “number one” urology department in the nation (as consistently rated in U.S. News and World Report). A recent issue of their October 5th, 2011 Health Alerts  (see link) provides a good summary of external beam radiation therapy.

Hormonal Therapy and Osteoporosis – New Options.

Near Bryce Canyon Utah; bj gabrielsen

Osteoporosis (bone loss) is one of several side effects which accompany androgen deprivation (hormonal) therapy (ADT). Fifty (50) percent of men will be affected by their fourth year of treatment, and more than 80 percent will be affected after10 years. The risk of fractures including those of the spine also increases with hormonal therapy treatment for a year or more. This enhanced risk is illustrated by a recent study in The New England Journal of Medicine where it was reported that “among men with prostate cancer who lived for at least five years after their diagnosis, the risk of a fracture was nearly 20 percent among androgen deprivation (hormonal) therapy users, compared with 13 percent for nonusers.” Men treated with hormonal therapy are generally advised to have annual bone density testing.

Medications are also often prescribed to halt bone loss. The well-known bisphosphonates (such as Fosamax) are the first treatments prescribed followed by selective estrogen receptor modulators (SERMs) such as tamoxifem, used in the treatment of breast cancer. For prostate cancer patients, a new alternative, a monoclonal antibody called denosumab (brand names Xgeva or Prolia), is now generating much attention. Denosumab is an injectable monoclonal antibody. Monoclonal antibodies are made to target and destroy only certain cells in the body thereby helping to protect healthy cells from damage. Xgeva is used to prevent bone fractures and other skeletal conditions in people with tumors that have spread to the bone.  Prolia is another brand of denosumab used to treat osteoporosis in postmenopausal women who have high risk of bone fracture. In November 2010, the Food and Drug Administration (FDA) approved Prolia (Xgeva) to help prevent skeletal-related events in prostate cancer patients treated with hormonal therapy whose cancer had already metastasized to bone. The use of this therapy has recently been expanded. On Friday, September 16, 2011, the FDA approved denosumab (Prolia) in prostate cancer patients undergoing androgen deprivation (hormonal) therapy whose cancer had not yet metastasized to bone. Denosumab is also approved by the FDA for additional indications. The brand Prolia was approved by the FDA on June 1, 2010 for the treatment of postmenopausal women with osteoporosis who are considered to be at high-risk for fractures.

For more details, see the Johns Hopkins Health Alerts, “Prostate Cancer: Why You May be at High Risk for Osteoporosis,” Sept. 29th, 2011; and, “FDA Expands Approval for Denosumab”, NewsPulse from the Prostate Cancer Foundation, Sept. 30th, 2011;

NewsPulse, a Medical Resource from the Prostate Cancer Foundation. Biomarkers in Urine for the Detection of Prostate Cancer.

Sources of current medical information concerning prostate cancer are listed on this website under the section Medical Resources.  Recently, a new August 2011 electronic newsletter entitled NewsPulse was received from the Prostate Cancer Foundation. The issue contained very current information on specific diagnostic methods, biomarkers for cancer detection, targeted therapies and drugs under development, nutrition and genetics. One example follows below. Their e mail address is info@pcf.org. I would strongly recommend a subscription.

Biomarkers in Urine for the Detection of Prostate Cancer.

Biomarkers are usually genes, gene products or proteins and are found in various body fluids (blood, urine, cerebrospinal fluid). Their presence, absence and quantities are measured and used to diagnose various diseases and their stages. An example is prostate-specific antigen or PSA used to detect prostate conditions. The availability of an easy-to-use urine test that is specific in identifying the presence of cancer has the potential to eliminate thousands of unnecessary prostate biopsies in the U.S. each year. Thus the benefits of such biomarker tests below include identifying which patients actually require biopsies.

The June 1st, 2011 issue of the Johns Hopkins Health Alerts and the August issue of NewsPulse both describe two new biomarkers found in urine which may potentially be useful in detecting prostate cancer as opposed to other non-cancerous prostate conditions such as BPH (benign prostatic hyperplasia or enlarged prostate). The two specific biomarkers are: a) prostate cancer antigen or PCA3, which is expressed at high levels in 95 percent of prostate cancer patients; and, b) the DNA marker TMPRSS2:ERG gene fusion, a hybrid gene made from two previously separate genes, specifically the ERG and TMPRSS2 genes. This DNA marker is present in 50 percent of prostate cancer patients. The presence of this gene fusion is “thought to promote the development of prostate cancer and possibly a more aggressive form of the disease.”

PCA3 is made by a specific gene that produces the protein in 60-100 times more abundance in prostate cancer cells as compared to non-cancerous ones. According to Johns Hopkins, in order to be most predictive, the test for PCA3 should be done in conjunction with a digital rectal examination. PCA3 testing would not replace the usual PSA blood test but would help to either confirm or rule out the prospect of cancer in men with elevated PSA levels.

Patients with high levels of these biomarkers have been shown to have a 70 percent chance of having cancer with a 40 percent of it being a high grade cancer. There is also an association between test results and the size of the tumor in patients who do have cancer. It will take some time before the combined urine-based assay is widely introduced into practice. However, NewsPulse reports that the “University of Michigan has been offering the PCA3 test alone since earlier this year. They expect to be offering it in combination with TMPRSS2:ERG by the end of this year under a license agreement with GenProbe. Another trial using the combined assay will soon be conducted in cooperation with the Early Detection Research Network (EDRN). EDRN, an initiative of the National Cancer Institute (NCI), brings together dozens of institutions to help accelerate the translation of biomarker information into clinical applications and to evaluate new ways of testing cancer in its earliest stages and for cancer risk.”

“Once the University of Michigan begins offering the combined TMPRSS2:ERG/PCA3 test, physicians can send urine samples for analysis until the combined test is more widely available. For more information on this, men with questions about prostate cancer screening should speak to their doctors or call the U-M Cancer AnswerLine at 800-865-1125.”

As previously stated, the contents of this website are intended solely for information and encouragement. All medical decisions and actions should be made in consultation with a physician or appropriate medical personnel.

Information from Johns Hopkins: a) Use of Immunotherapies (Provenge, Prostvac) Against Prostate Cancer; and, b) Gleason Scores.

Broad Run-Middletown, MD; bj gabrielsen photo

Provenge (sipuleucel-T) was the first approved prostate cancer therapy which uses a person’s immune system to fight the disease.  Its approval was limited to men with advanced prostate cancer who have not responded to other treatments like hormonal (androgen deprivation) therapy and are experiencing few or no symptoms. Cost and supply remain significant issues hindering its widespread use. A recent article in the Johns Hopkins Health Alerts (September 8th, 2011) describes on-going studies involving the administration of Provenge under differing conditions. These include: a) combining Provenge with hormonal therapy in patients with earlier stage disease; b) combining Provenge with radiation therapy in hopes that the combination will have a greater effect than either of the two therapies alone (synergism); and, c) Phase 3 studies in men with early-stage, non-metastatic prostate cancer. Other immunotherapies in clinical trials include Prostvac (from the National Cancer Institute, National Institutes of Health) which may be less costly.

In another earlier issue of the Johns Hopkins Health Alerts (August 24th, 2011), the concept of the Gleason score is described. It is defined as a grade assigned to biopsied tumor cells to indicate a tumor’s potential aggressiveness. This tumor grade “reflects how far the cancer cells deviate from normal, healthy cells.” Gleason scores of 5 and 6 are generally classified as low-grade tumors, a Gleason score of 7 as intermediate and Gleason scores of 8, 9 and 10 as high grade, with the least favorable outlook.

 These Johns Hopkins Health Alerts and additional Bulletins written by Dr. Jacek Mostwin and colleagues are invaluable sources of current information for prostate cancer patients.

Countering Weight Gain as a Result of Hormonal Therapy.

Benefits and risks accompany virtually every method of treatment. Hormonal therapy for prostate cancer is no exception. Potential risks include osteoporosis and bone fractures, cardiac effects, diabetes, depression, hot flashes and metabolic changes resulting in weight gain. (These issues are discussed on this website under “My Story”, 2009 entries of July 5th-27th, September 29th, October 20th, November 25th, and December 6th, as well as March 12th, 2010.) I have been on continuous or intermittent hormonal therapy since August, 2006. Fortunately, my side effects have been minimal although I had gained approximately fifteen pounds. I was told by a urologist that it was difficult to lose weight while on hormonal therapy. Eventually however, I was determined to lose these unwanted pounds. It has not been easy but I have lost most of the weight while continuing my therapy. I found that once I made up my mind to lose the weight, it was indeed possible with diet and exercise. Here are some practical tips I learned along the way.

Personally, it helped to make an initial investment and enroll in one of the popular advertised weight loss programs. It did not take long to begin to understand their general principles and one could discontinue enrolling after a month or so thus saving money. The diets in general consisted of very low-fat, low-carbohydrate meals with moderate protein content. I found the following strategies to be helpful.

1) Eat a fairly substantial breakfast of whole-grain cereals, fruits and light soy or low-fat milk; eggs (omelets) can be substituted.

2) Eat about 5 small meals a day and eat less as the day progresses. Mid-morning and mid-afternoon 100-calorie snacks (cheese, yogurt, fruit) were useful in curbing hunger.

3) If possible, eat dinner at mid-day and your usual lunch as the evening meal. Low fat meats such as chicken, turkey, lean beef (ground sirloin, lean roast beef) as well as fish become staples. Bread was limited to 1-2 slices of 40-calorie whole grain bread daily. Fresh vegetables and salads with low-fat dressing are of course encouraged. Low-fat mayonnaise is recommended but I personally found that one could never fully replace the flavor of real mayonnaise, so I used it in moderation.

4) Sip on water during the day; drinking an 8 oz. glass before meals helped me eat less while feeling satisfied. Diet drinks can be used but I found that water alone was best in satisfying my hunger.

5) Exercise is a must. Aerobic and weight-bearing exercises are also good for healthy bones. My wife and I exercise for 60 minutes in a gym three-times a week.

6) Minimize the use of alcohol, although a small glass of wine on occasions can be incorporated.

7) To satisfy my salt craving, pretzels seemed to be lowest in calorie content.

8) Don’t eat within three hours of bedtime except for a small piece of fruit or similar low calorie snacks. Midnight snacks are forbidden.

9) The eventual goal is portion control. I found that after a few weeks, my hunger was fully satisfied with 33% less food than I had previously consumed. Maintaining this level remains my goal.

Pomegranate Extract Slows PSA Doubling Time.

Cancer researchers led by Dr. Michael Carducci at the Johns Hopkins Hospital in Baltimore, MD recently reported the results from studies funded by POM Wonderful to investigate the potential benefits of their POM-X pomegranate extract. The results were reported at the February 2011 American Society of Clinical Oncology (ASCO) Genitourinary Symposium. PSA doubling time in 104 men taking 1,000 mg or 3,000 mg (milligrams) of the extract increased from a median of 11.9 months before taking POM-X to 18.5 months after taking the extract. “There was no significant treatment difference between the different dosages on PSA doubling.” According to a recent article in the March 2011 issue of the Prostate Cancer Research Institute (PCRI) Insights (Vol. 14, No.1, http://www.prostate-cancer.org/pcricms/node/59), “This implies that cancer growth is slowed. It is hoped (but not yet proven) that doubling times induced by POM-X will result in longer time to progression and improved lives for men with prostate cancer.”

This study reinforces a smaller 2005-6 study at UCLA wherein men drinking 8 oz. daily of POM Wonderful pomegranate juice experienced longer PSA doubling times. A research group led by Dr. Manuela Martins-Green had determined that pomegranate juice concentrate increased cell death in prostate tumor cell lines that were resistant to testosterone (which are associated with metastasis), increased cell adhesion and decreased migration in prostate cancer cells that survived. More recently, it was reported at the American Society for Cell Biology’s December 12th, 2010 meeting that specific families of chemical compounds isolated and identified from the pomegranate extract inhibited the migration of cancer cells and their attraction to a signal that promotes metastasis to the bone.

Neither of these above studies had a placebo arm so it is not unequivocally proven that the pomegranate actually caused the improvement. One can read about this study and others in the PCRI Insights Newsletter (see below). One such example is “Pomegranates and Prostate Health: A Research Report” available at http://www.prostate-cancer.org/pcricms/node/112.  The useful PCRI Insights are also available by mail. Their contact information is 5777 West Century Blvd. Suite 800, Los Angeles, CA 90045; phone: (310) 743-2116; helpline: (310) 743-2110; e mail: pcri@pcri.org; web address: www.prostate-cancer.org and www.pcri.org.

As always, material on this website is presented for information purposes only. Significant interactions between natural food products and various medications are possible. The reader is urged to consult their health professional before using any new substances or products.

Avodart (dutasteride) used to treat benign prostatic hyperplasia (BPH) may slow the growth of early-stage prostate cancer

A recent study presented on Feb. 17-19th  at the 2011 Genitourinary Cancers Symposium in Orlando, FL by researchers from the University Health Network in Toronto, Canada concluded that for men who are undergoing “watchful-waiting” for prostate cancer, Avodart could help control the disease and prevent the need for more aggressive treatments. “Watchful waiting,” or active-surveillance refers to the practice of foregoing immediate treatment after a prostate cancer diagnosis in favor of regularly-scheduled testing and clinical exams to closely monitor the disease.

Avodart (dutasteride) is already approved by the Food and Drug Administration (FDA) for the treatment of an enlarged prostate gland, or benign prostatic hyperplasia (BPH). The drug inhibits an enzyme called 5-alpha reductase, which converts testosterone into its more potent form, dihydrotestosterone. In addition to BPH, 5-alpha reductase drugs are also used to treat prostate cancer and baldness. Further details from the study can be found in the Feb. 22, 2011 issue of the National Cancer Institute (NCI) Cancer Bulletin. ”In the dutasteride group, 38 percent of the 302 men enrolled in the study experienced some progression of their cancer, compared with 49 percent of the men in the placebo (control) group. This difference translated into a reduction of relative risk for cancer progression of 38.9 percent in the dutasteride group. In addition, taking dutasteride increased the chances that no cancer would be found during a participant’s final biopsy. Thirty-six percent of the men in the dutasteride group and 23 percent of the men in the placebo group had no cancer detected in their final biopsy specimens.” The researchers suggested that it could be “very reasonable” to give a 5-alpha reductase inhibitor such as dutasteride to patients with “ultra low-risk” prostate cancer who elect for “watchful waiting”. It was also noted that the FDA’s Oncologic Drugs Advisory Committee had previously rejected GlaxoSmithKline’s application for dutasteride for use in preventing prostate cancer.

A word of caution regarding the Avodart study described above was recently published on March 9th in the Johns Hopkins Health Alerts: Prostate Disorders. The Hopkins physicians stated that it was unclear whether Avodart actually prevents prostate tumors or simply reduces the chance of a diagnosis. They noted that in the above study, “more people in the placebo group than in the Avodart group received a diagnosis of prostate cancer during the four-year study: 25% versus 20%.  While these findings may sound like good news, it’s possible that Avodart simply suppressed PSA levels, rather than preventing the development of new cancers. Another concern: More men in the Avodart group than in the placebo group were diagnosed with a tumor with a high Gleason score — the tumors most likely to be lethal. ” The Johns Hopkins physicians advised that “if you take Avodart for any reason, be sure that the doctor who performs your PSA screening test is aware of this information. Because Avodart may simply be suppressing your PSA level, he or she will need to perform a mathematical calculation to determine your “true” level. “