Prostate Cancer Screening Needs a Massage!
Nov 20, 2009 | The HWN Team | Cutting Edge
PSA screening creates more problems than the cancer itself and as a result just about every major organization is no longer recommending routine PSA screening
PSA screening for prostate cancer has become a hot potato. In May 2012 after exhaustive review of the benefits and risks of PSA screening the United States Preventive Services Task Force (USPSTF) released its final recommendation for prostate cancer screening; recommending against routine PSA-based screening for all men, regardless of age.1
Their conclusions were based on several studies including two large-scale studies on the risks and benefits of PSA testing which were published in the New England Journal of Medicine in 2009. Instead of settling the PSA question once and for all, the two studies actually produced somewhat contradictory results.
In the American study, 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".2
In the European study, 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.3
According to WHO prostate cancer is the sixth most common cause of cancer death in men worldwide and was estimated to be responsible for almost 258,000 deaths in 2008. Prostate cancer is the second most common cancer in male Americans after skin cancer and is the second death-causing cancer in American men after lung cancer. It accounts for about 10% of cancer-related mortalities in men.4,5
On the other hand, the prognosis for prostate cancer is quite good. This is because prostate cancer is usually a slow-growing disease and many of those diagnosed do not develop symptoms. According to ACS about 1 man in 6 will be diagnosed with prostate cancer during his lifetime, but only 1 man in 35 will die of it. and for all men with prostate cancer, the relative 5-year survival rate is nearly 100% and the relative 10-year survival rate is 93%. The 15-year relative survival rate is 79%.6
So, why is the PSA screening so unreliable?
The ACS states that the PSA test is not 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.7
Prostate-Specific Antigen is a substance naturally occurring in the male semen but can also occur in small amounts in the blood. Furthermore to confound things, several factors and conditions can affect the PSA levels in the blood and create confusion in the diagnosis:
- 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.
Although PSA screening can detect early cancer it 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.
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. However, 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.
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. And according to the ACS "uncertain or false test results 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".
But, what about the other screening tests?
The digital rectal exam or DRE is uncomfortable, invasive and even less sensitive than the PSA.
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.8
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.9
Essentially, PSA screening is still the best we have! Meanwhile, while we wait for better screening methods for prostate cancer, several new treatment trends have emerged.
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.10,11
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.12,13
Cancer vaccines - 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.14
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.15
Recent results from a Phase III clinical trial involving the therapeutic vaccine Provenge, manufactured by Dendreon Corporation showed that men with advanced prostate cancer lived an average of 4 months longer than men who did not receive it. However, while the drug prolonged life span, it does not slow down disease progression. Dendreon received FDA approval for Provenge but it continues to remain controversial.16
Another vaccine in the making is PROSTVAC which is made from a virus that has been genetically modified to contain PSA. The patient's immune system should respond to the virus and begin to recognize and destroy cancer cells containing PSA.
Supplements - 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.17
The Bottom Line
Hats off to the USPSTF for taking a stand against the status quo - the evidence is overwhelming. However, without a doubt there will be teeth gnashing over the latest recommendation - no more routine PSA screening. Yet, there still isn't a screening test that is better than the PSA.
On the bright side the emphasis has shifted from screening all men to those that are at highest risk such as African Americans or those with a positive family history as well as stimulating the quest for better screening tests and management techniques, especially in the non-invasive arena.
In the interim, 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. Meanwhile, prostate cancer screening continues to need a massage!
Published November 20, 2009, updated May 31, 2012
- Task Force Recommends Against PSA-Based Screening for Prostate Cancer, Science Daily, May 21, 2012
- Andriole GL et al, Mortality results from a randomized prostate-cancer screening trial, N Engl J Med. 2009 Mar 26;360(13):1310-9
- Schröder FH et al, Screening and prostate-cancer mortality in a randomized European study, N Engl J Med. 2009 Mar 26;360(13):1320-8
- Prostate cancer mortality statistics, Cancer Research UK
- Prostate Cancer: Weighing Options, Wall Street Journal, April 7 2009
- Prostate Cancer, American Cancer Society
- Can prostate cancer be found early?Prostate Cancer, American Cancer Society
- Transrectal ultrasound (TRUS), BUPA, February 2011
- Sanderson K, Prostate cancer marker found in urine, Nature, February 2009
- Freezing Prostate Cancer Does a Man’s Body Good, Society of Interventional Radiology
- Prostate Cancer Cryotherapy, GalilMedical
- High Intensity Focused Ultrasound, USHIFU
- Nomura T, Focal therapy in the management of prostate cancer: an emerging approach for localized prostate cancer, Adv Urol. 2012;2012:391437. Epub 2012 Apr 24
- Cancer Vaccines, National Cancer Institute
- Powell K, Designer immune cells fight prostate cancer, Nature, 20 April 2009
- Begley S, Insight: New doubts about prostate-cancer vaccine Provenge, Reuters, Fri Mar 30, 2012
- Lippman SM, Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT), JAMA. 2009 Jan 7;301(1):39-51. Epub 2008 Dec 9
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