The progress of developing new treatments for advanced prostate cancer continues. MDV3100 (now called enzalutamide) is being developed by Medivation Inc. and Astellas Pharma Inc. It is now available in eleven states as part of additional clinical trials in prostate cancer patients who have failed hormonal therapy and who have been previously treated with docetaxel (taxotere). Enzalutamide (MDV3100) had earlier demonstrated positive Phase III clinical trial results in men with hormone-refractory prostate cancer who had or had not undergone chemotherapy with taxotere (docetaxel). On this basis, it had been placed on a fast-track for approval by the Food and Drug Administration. The drug works by disrupting a tumor cells’ ability to use testosterone by blocking the cell’s testosterone receptors thus preventing the production of androgens (testosterone) within the cell itself. It is an oral, androgen receptor antagonist and does not require co-administration of steroids such as prednisone. For further information, see the clinical trial information found in this link. MDV3100 is included on a list of prostate cancer treatments under development and has been posted on this website in the 2012 blog dated January 3, 2012.
Since its October, 2011 initial advisory, and after receiving input from the medical community including many leading urologists and oncologists, the United States Preventative Services Task Force (USPSTF) recently issued its final recommendation against screening asymptomatic men for prostate cancer using the prostate-specific antigen (PSA) test. (An earlier 2008 recommendation had advised against screening men over the age of 75.) The USPSTF conclusions are discussed in the May 29th, 2012 issue of the National Cancer Institute Bulletin among other sites below. The USPSTF panel concluded that routine diagnostic PSA screening could not be clearly demonstrated to save lives and its potentially-significant harms (such as false positive results, biopsy-related infections, potential incontinence and erectile dysfunction) outweigh any small potential benefits. However, PSA testing will still be used to monitor progression of prostate cancer after its diagnosis or treatment. Medicare is expected to continue to pay for such PSA evaluations. It must be noted that the USPSTF did not include any urologists nor medical oncologists on their panel. For a full listing of the Task Force members, their affiliations and their specific fields of expertise see http://www.uspreventiveservicestaskforce.org/members.htm. Strong criticisms of this recommendation have been issued by noted American urologists as well as medical and professional organizations such as the American Urological Association and the National Comprehensive Cancer Network. Additionally, a dissenting opinion was published in the Annals of Internal Medicine by some of the leading clinical scholars in prostate cancer care, including Dr. William Catalona, Medical Director of the Urological Research Foundation and Dr. Patrick C. Walsh, University Distinguished Service Professor of Urology at Johns Hopkins. These experts believe the USPSTF overestimated the harms and underestimated the benefits of PSA screening in the United States. Much of the discussion centered upon two separate clinical trials; the National Cancer Institute (NCI)-funded Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC). A recent study involving 20,000 Swedish men over a 14-year period has been cited as strong evidence that PSA screening does indeed save lives. (See the May 29th issue of the ZeroHour Newsletter). For an overview of affirming and dissenting opinions from various groups, see the Prostate Cancer Research Institute (PCRI) Weekly for May 30th, or the May, 2012 PCRI NewsPulse.
In light of these new recommendations, what should a man do at this point? The most important need is a shared decision-making process between a man and his trusted physician. Individual patient factors such as age, medical condition, symptoms (or lack thereof), family history, ethnicity or concerns about prostate cancer must form the basis of a rational decision between a patient and his physician to undergo PSA testing. As stated in the Prostate Cancer Foundation Newsletter, “the USPSTF’s position provides a teachable and actionable moment for the medical community to improve targeting of PSA screening in patients, reduce over-testing and improve processes of patient education on the risks of overtreatment from PSA screening.” See also the June 2012 edition of Prostate Cancer Advances, “PSA: Better Patient Education.”
Finally, targeted screening using specific biomarkers is urgently needed to identify and differentiate between aggressive cancers requiring treatment and those best followed by “active surveillance”. Examples of such biomarkers include a urine test to identify abnormally high levels of genetic RNA made from the PCA3 gene in prostate cancer cells. This urine test commercialized by Gen-Probe and known as PROGENSA PCA3, was approved by the Food and Drug Administration (FDA) in February of this year. A National Cancer Institute (NCI) study examined the predictive value of using PROGENSA PCA3 to detect prostate cancer. A positive PCA3 test predicted a positive biopsy of 80 percent of the time at initial biopsy; and, for men undergoing repeat biopsies, a negative urine test predicted a negative biopsy 88 percent of the time.
Still another example of a potential biomarker being studied at Cornell, MIT and Harvard Universities is the identification of mutations in a gene called SPOP. Such genetic alterations may be unique to early stage prostate cancer. These are just two examples of potential targeted screens which hopefully will one day replace the PSA test to provide more precise information to guide physicians and their patients in their diagnoses and possible treatments if necessary.