
Currently worldwide prostate cancer screening is still dependant on the PSA blood test and the Digital rectal exam.
(1) The PSA blood test remains the state-of-the-art screening method for prostate cancer. PSA stands for Prostate-Specific Antigen. It is a substance naturally occurring in the male semen but can also occur in small amounts in the blood. A normal PSA blood level is about 4 nanograms per milliliter (ng/mL). Elevated levels of PSA in the blood can indicate an increase in the number of cancerous cells. However, it may not, hence the reason the PSA test remains controversial.
(2) The Digital rectal exam or DRE is performed by inserting a lubricated gloved finger into the rectum of the patient to feel for bumps and other abnormalities that might be indicative of cancer. This is possible because the prostate gland is just right in front of the rectum. However, some patients may consider a rectal exam uncomfortable and invasive. It is also less sensitive than PSA.
Unfortunately making an initial accurate diagnosis of prostate cancer is not easy due to the nature of the disease and the limitations of current screening methods.
(1) The ACS states that neither the PSA test nor the DRE is 100% accurate. Abnormal results of these tests don't always mean that cancer is present, and normal results don't always mean that there is no cancer. In fact, some experts contend that prostate cancer is overdiagnosed because of the unreliability of the PSA test. According to the ACS "uncertain or false test results could cause confusion and anxiety. Some men might have a prostate biopsy (which carries its own small risks, along with discomfort) when cancer is not present, while others might get a false sense of security from normal test results when cancer is actually present".
(2) Furthermore to confound things, several factors and conditions can affect the PSA levels in the blood and create confusion in the diagnosis. These are, according to ACS:
Benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the prostate that occurs with age can increase PSA levels.
Age: PSA levels will also normally go up slowly as you get older, even if you have no prostate abnormality.
Prostatitis, an infection or inflammation of the prostate gland can elevate PSA levels.
Ejaculation can cause the PSA to go up for a short time, and then go down again. Medications: Certain medicines or herbal mixtures can interfere with PSA measurements.
Obesity: Obese men tend to have lower PSA levels.
(3) In early 2009, two large-scale studies on the risks and benefits of PSA testing were published in the New England Journal of Medicine. Unfortunately, instead of settling the PSA question once and for all, the two studies actually produced somewhat contradictory results.
In the American study on PSA, researchers followed up 76,693 men for 7 to 10 years who either had a PSA test or a DRE and compared mortalities due to prostate cancer. The study results showed that "the rate of death from prostate cancer was very low and did not differ significantly between the two study groups."
In the European study on PSA, researchers followed up about 182,000 men who either had PSA or no PSA testing and compared mortality rates. The study results showed that "PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis.
Although the screening tests can detect early cancer they cannot determine whether the cancer will prove to be fast-growing and aggressive or slow growing and benign. For patients and health care providers alike, this lack of clarity in the tests results creates a dilemma: treat the cancer before it spreads any further or do nothing but practice what is called "watchful waiting" or "expectant management" with serial PSAs and eventual biopsy. As a result of the PSA test's shortcomings there tends to be overdiagnosis which creates overtreatment - too many invasive biopsies and serial blood tests which consumes precious healthcare resources and productivity.
Other screening tests have been developed but due to limitations have not replaced the conventional screening tests.
(1) Transrectal ultrasound (TRUS) uses ultrasound technology to view the prostate gland by inserting a small electronic probe into the rectum. However, TRUS is usually not used as a routine screening test for prostate cancer because its low detection power may not reveal early stage cancer. However, TRUS is a useful method used in conjunction with a prostate biopsy. It helps guide the biopsy needle into the right area of the prostate. It can be useful in other situations including measurement of the size of the prostate gland and as a guide during cryosurgery.
(2) Urine test for prostate cancer. A recent study has identified a molecule in the urine of men that could be used as a disease marker in prostate cancer patients. The molecule has been identified by researchers at the University of Michigan in Ann Arbor as sarcosine "a derivative of the amino acid glycine. Sarcosine was discovered after close inspection of all the metabolites found in 262 samples from prostate cancer patients — all of whom had different stages of the disease — including benign cells to aggressive metastasized cancers able to spread to other organs. Metabolites are the substances involved in or produced by the chemical reactions that take place in the body, and the concentrations of these chemicals can change as cancer progresses." (Source: Nature News). However, the technique is still used primarily for the staging of prostate cancer.
And to add insult to injury if supported by a positive biopsy, chances are that doctors will recommend treatment which usually involved surgical removal of the gland, the so-called prostatectomy. Unfortunately, this conventional and invasive treatment can have the following side effects: interference with sexual function, interference with urinary function, psychological distress and lower quality of life.
However, on the bright side, while we wait for better screening methods for prostate cancer, several new treatment trends have emerged in the fields of cryoablation and immunotherapy.
(1) Interventional cryoablation. At the 34th Annual Scientific Meeting of the Society of Interventional Radiology, researchers presented results of a revolutionary and minimally invasive way of treating prostate cancer. Focal cryoablation is the male equivalent of a lumpectomy (e.g. as in breast cancer) which entails localizing the tumor and destroying it by freezing or cryosurgery. With cryoablation, interventional radiologists insert a probe through the skin, using imaging to guide the needle to the tumor; the probe then circulates extremely cold gas to freeze and destroy the cancerous tissue. This minimally invasive treatment targets only the cancer itself, sparing healthy tissue in and around the prostate gland rather than destroying it, as traditional approaches do.
(2) High Intensity Focused Ultrasound (HIFU) looks promising. This minimally invasive prostate cancer therapy as described by the International HIFU " is a therapy that destroys tissue with rapid heat elevation, which essentially "cooks" the tissue. Ultrasound energy, or sound waves, is focused at a specific location and at that "focal point" the temperature raises to 90 degrees Celsius in a matter of seconds. Over 7000 men, in nearly 100 HIFU centers worldwide, have already chosen HIFU with the Sonablate® 500, because it is the most advanced HIFU therapy available." The procedure is not approved in the United States but is undergoing clinical trails.
(3) Cancer vaccines. According to the US National Cancer Institute cancer vaccines are medicines that belong to a class of substances known as biological response modifiers. Biological response modifiers work by stimulating or restoring the immune system’s ability to fight infections and disease.
There are two broad types of cancer vaccines: Preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people; and Treatment (or therapeutic) vaccines, which are intended to treat already existing cancers by strengthening the body's natural defenses against cancer. Currently, no cancer vaccine has been approved for the indication of prostate cancer but there are several drugs in development.
Researchers at the Roger Williams Medical Center in Providence, Rhode Island are developing "designer immune cells" to treat prostate cancer. They removed T-cells from patients and genetically engineered them to recognize prostate-specific membrane antigen, or PSMA which are found on the outer membrane of prostate cells. The biological drug is currently being tested in Phase I trials.
The therapeutic vaccine Provenge, manufactured by Dendreon Corporation, is showing a lot of promise. The recent results from a Phase III clinical trial showed that men with advanced prostate cancer who received Provenge lived an average of 4 months longer than men who did not receive it. The drug uses the immune system of the patient to fight cancer. However, while the drug prolonged life span of the patients, it does not slow down disease progression. Dendreon is planning to apply for US FDA approval for Provenge later this year.
Another vaccine in the making is PROSTVAC-VF which is made from a virus that has been genetically modified to contain prostate-specific antigen (PSA). The patient's immune system should respond to the virus and begin to recognize and destroy cancer cells containing PSA.
Of interest one of the largest studies on the effect of vitamin supplements on prostate cancer produced rather disappointing results and had to be stopped prematurely. The National Cancer Institute SELECT trial investigated whether supplementation with vitamin E, selenium, or a combination of the two can lower the risk of prostate cancer. Unfortunately, the results after five years revealed otherwise. In fact, study participants who took only vitamin E actually had a slightly increased risk of developing prostate cancer while those taking only selenium seemed to have a slightly increased risk of developing diabetes.
Currently, no major scientific or medical organization, including the American Cancer Society (ACS), American Urological Association (AUA), US Preventive Services Task Force (USPSTF), American College of Physicians (ACP), National Cancer Institute (NCI), American Academy of Family Physicians (AAFP), and American College of Preventive Medicine (ACPM) support routine testing for prostate cancer at this time.
However, the PSA test still remains the so called gold standard for screening for prostate cancer. And on the bright side, PSA test unreliability has and is stimulating the quest for better management techniques, especially in the non-invasive arena, and better screening tests. Healthcare providers should openly talk with their patients about the benefits, risks, and uncertainties of prostate cancer screening so that men can "weigh their options" and make "informed decisions" about this issue.
In the meantime prostate cancer screening continues to need a massage!
References
American Cancer Society. Can Prostate Cancer Be Found Early?
American Cancer Society. What Are the Key Statistics About Prostate Cancer?
Boyles S. Prostate Cancer Provenge Strong in Trial. WebMD
National Cancer Institute. Cancer Vaccines.
Powell K. Designer immune cells fight prostate cancer NatureNews 20 April 2009.
Prostate Cancer: Weighing Options. Wall Street Journal.
Sanderson K. Prostate cancer marker found in urine. NatureNews February 2009
Society of Interventional Radiology. Freezing Prostate Cancer Does a Man’s Body Good.
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