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.

Variations in Five Genes May Identify Lethal Varieties of Prostate Cancer.

Danger lurks in southwest Florida; bj gabrielsen photo

For years, the general practice used in the initial screening for prostate cancer is a blood test for prostate-specific antigen (PSA) in conjunction with a digital rectal examination. These tests are then used to determine whether or not to subject the patient to a prostate biopsy, inherent with its own side effects and hopefully negative results. If the biopsy reveals cancer, then the questions of whether or not to treat the cancer, what treatment(s) would be most effective while minimizing potential side effects, and the possibility of no treatment or “watchful waiting” must be addressed. It would be extremely useful if a blood or urine test could identify genetic biomarkers (genes and their products such as proteins) whereby physicians could determine not only the presence or absence of prostate cancer but be able to predict whether or not the cancer would require treatment and if so, should aggressive treatment be necessary. For the many cases of prostate cancer which are identified, ‘no one size of treatment fits all.’ Methods are sorely needed to determine the appropriate level of treatment, if any.

More than 25 genetic subtypes of prostate cancer have been already identified. Some of these cancers might never require treatment and a man could die of other causes while other cancers require immediate, aggressive treatment. A team of researchers from Seattle and Sweden have recently identified a set of variations in five (5) genes which may be signatures for lethal prostate cancer thereby requiring aggressive treatment. These genetic variants might serve as the basis for a new blood test that could be given on initial diagnosis in order to determine which patients need aggressive treatment versus “watchful waiting.” To discover the five “disease genes” implicated in lethal prostate cancers, researchers looked for genetic variants that prostate cancer patients share in common. These variants in genes are called single-nucleotide polymorphisms, or SNPs (pronounced “snips”). Genes can be depicted as chains of thousands of beads comprised of four-five basic colors all arranged in a specific sequence. An example of a SNP would be the substitution of one blue bead in a gene by a red bead at a specific location along the chain of thousands of colored beads. These inherited genetic variants are certain genes that may signal the development of fatal varieties of prostate cancer. The five SNPs that were identified were linked to five genes that may affect prostate cancer progression, namely LEPR, RNASEL, IL4, CRY1, and ARVCF.  It was of special interest to note that two of the five genes studied (IL4 and RNASEL) were associated with inflammation of the prostate, thereby suggesting a possible link between chronic inflammation of the prostate and the triggering of prostate cancer. The state of this research requires much more validation and development before it could be used as a diagostic test for aggressive prostate cancer. But it is a significant finding and indicative of the type of biomarker which would eventually relieve the uncertainties associated with PSA tests.

The research findings were published in the September issue of Cancer Epidemiology, Biomarkers and Prevention, and summarized in the September 2011 issue of NewsPulse from the Prostate Cancer Foundation.

Prostate Cancer Stem Cells: A New Target for Treating Hormone-Refractory Cancer.

It has been known for over 60 years that in general, prostate cancer cells respond to androgen deprivation (hormonal) therapy. At some point however, the prostate cells no longer respond (they become hormone-refractory) and levels of prostate-specific antigen (PSA) begin to rise. Treating this hormone-refractory prostate cancer remains a major challenge. There is now evidence that the resulting hormone-refractory solid tumors originate from undifferentiated (less-specialized) stem cell-like cells which are thought to only comprise 0.1 percent of the original prostate tumors. Metastasis also arises from these stem cell-like cells. [Stem cells are found in all multicellular organisms; they can divide and change from being less-specialized into more-specialized cell types as well as producing more stem cells.]  These cancer stem cell-like cells often do not respond to chemotherapy or hormonal therapy, so a different approach that attacks these cells in advanced prostate cancer is needed.

In a recent report on Prostate.net and in the September 20th, 2011 ZeroHour Newsletter, a Swedish research team has found that a protein called STAT3 is active in the stem cell-like cells. In addition, a natural compound called galiellalactone was found to have an effect on STAT3 and inhibits prostate cancer growth. This research represents only the initial stages of the process of developing a drug that will attack the stem cell-like cells. Using the known compound galiellalactone as a model, other better drug-like substances will hopefully be identified that will inhibit STAT3 and become new therapies that attack the stem cell-like cancer cells in men who have prostate cancer and prevent growth and spread of the disease.

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;

Bone Scans for Metastatic Prostate Cancer

Sanibel, FL; photo BJ Gabrielsen

The most troubling thought for prostate cancer patients whose cancer has recurred after an initial radicalprostatectomy is the fact that there are PSA-producing cells located somewhere in our bodies. While subsequent treatments such as androgen deprivation (hormonal) therapy may keep these cells under control, there are undoubtedly micro-metastases somewhere in our bodies. When the controlling therapies are discontinued, the cells begin to multiply and PSA rises. Bone scans are generally prescribed to identify sites of metastases. The scans involve the injection of a small amount of a radioactive element, technetium-99 (as technetium Tc 99m medronate). Greater than 90% of the mild radiation produced is eliminated from the body in 24 hours. It is generally accepted that technetium Tc 99m medronate is deposited on the surface of hydroxyapatite crystals, a mineral form of calcium, which comprises up to 50% of bone. Rapidly dividing tumor cells require enhanced blood flow (a process called angiogenesis) in order to grow.  Enhanced blood flow and / or blood concentration is most important in the delivery of the technetium-99 reagent to sites of uptake. Therefore, actively dividing cancer cells in bone would be specifically targeted. In addition to areas of abnormal osteogenesis (bone formation) such as those that occur with metastatic bone disease, other non-cancerous conditions such as Paget’s disease, arthritic disease, osteomyelitis (bone infection), and fractures can also be identified in a bone scan. Bone scans may not always be recommended as long as a patient’s PSA levels are not increasing. In my own case, even though my PSA had remained at very low or at undetectable levels, my Johns Hopkins urologist recommended a bone scan since I had not had one in seven years. His rationale was that even though the likelihood of seeing bone metastases is small, nonetheless, the disease can progress on hormonal deprivation therapy even if the PSA is low. Small quiet progression, if it is found, is something to be noted and followed. Thank God, my bone scan showed no evidence of metastatic cancer but it “lit up like a Christmas tree” since it revealed areas of formerly-broken bones (ankle, wrist, ribs) and arthritis in my lower spine and right hip which had been replaced in 1991. Physicians may differ in their prescriptions for bone scans. Therefore this website commentary is for information purposes only and should be utilized only after discussion with your personal health care provider.  Since this blog was initially written, an excellent review article entitled “Imaging Studies for Prostate Cancer: What to Expect” was published in the October 20th, 2011 edition of the Johns Hopkins Prostate Disorders Health Alert. The article goes into more detail about when bone scans should be prescribed, ProstaScint scans for metastases to lymph nodes or small organs and the uses of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) scans.