Should You Get a PSA Blood Test?

Photograph courtesy of Joint Base Lewis McChord via Creative Commons

My brother-in-law was seemingly the healthiest person I knew. He never even got a cold, so he rarely saw the doctor. Luckily he got a complete checkup when he turned 50, because it turned out that he had aggressive prostate cancer. Standard screening, to find prostate cancer in people who don’t have symptoms, allowed him to be treated in time.

Standard prostate cancer screening consists of a digital (finger) rectal exam to feel for prostate abnormalities and a simple blood test that measures the amount of prostate-specific antigen (PSA) in the blood. PSA is a protein produced by the prostate gland that is present in small quantities for healthy men, but it’s generally evaluated for men with prostate cancer and other prostate disorders. The goal of PSA screening is to detect prostate cancer early, so it is easier to treat and more likely to be cured.

So why has PSA screening recently become so controversial when it’s just a simple blood test? The main issue is that PSA screening isn’t good at distinguishing between aggressive life-threatening prostate cancer and slow-growing prostate cancer that may never spread. So it may lead to unnecessary side effects from overtreatment of slow-growing prostate cancer, including a risk of incontinence and impotence.

This controversy escalated in May 2012 when a government panel of health experts called the U.S. Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer for men of any age, stating that the benefits of screening don’t outweigh the harms of overtreatment.

The USPSTF based its recommendation primarily on the two largest published randomized clinical trials that evaluated the effectiveness of PSA screening. The first is the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial in which 76,685 men aged 55 to 74 years were randomly assigned to receive either annual PSA screening or “usual care.” The study found that slightly more prostate cancers were found in the PSA screened group, but the number of people that died from prostate cancer were about the same for both groups. Hence, it raised the question of whether men were harmed from overtreatment of cancers that weren’t life threatening.  However, this PLCO study is inherently flawed because 52% of the “usual care” control group also received PSA screening and 40% of the study participants received PSA screening before enrollment in the trial. Since so many men in the “usual care” control group received PSA screening, it’s not surprising that the prostate cancer mortality rates were the same for both groups.

The USPSTF also based its recommendation on the European Randomized Study of Screening for Prostate Cancer (ERSPC) that randomly assigned 162,243 men aged 55 to 69 years to either PSA screening once every 4 years or an unscreened control group. After correcting for patients that did not follow the protocol-prescribed screening procedures, the ERSPC found that PSA screening actually reduced the risk for dying of prostate cancer by 31%. Many argue that this demonstrates that PSA screening has a significant benefit, so it’s unclear how the USPSTF considered these results in their benefit to harm analysis.

An ad hoc group of nationally recognized prostate cancer medical experts have argued against the USPSTF recommendations. They state, “We believe that eliminating reimbursement for PSA testing would take us back to an era when prostate cancer was often discovered at advanced and incurable stages.”

A journal article published in the July 2012 issue of Cancer supports the view of this ad hoc group. Researchers at the University of Rochester Medical Center used data from the Surveillance, Epidemiology and End Results Program to estimate the total number of men in the current U.S. population who would have metastatic prostate cancer at initial diagnosis if PSA screening weren’t used. Such metastatic prostate cancer is usually rapidly fatal with a median survival of less than 1 yr to 2.6 years, depending on age.  The study found that there would have been 25,000 men presenting with metastatic disease in 2008 in the absence of PSA-screening, instead of the 8,000 men that were actually observed using PSA-screening.

So the uncertainty and controversy about PSA screening continues despite extensive research. Since I work in the field of prostate cancer research, friends and family members have asked my opinion. It seems to me that the new screening guidelines against PSA testing assume that ignorance is less stressful than having faith in your doctor; specifically, it’s better to not even perform a simple PSA blood test because patients with low PSA levels are often over-treated. Why not just change how to treat patients with low PSA levels and repeat the blood test in 6 months to a year to see how quickly the PSA level rises — since prostate cancer is more likely to cause a rapid rise in PSA levels? Is this common practice of “watchful waiting” by your doctor really more stressful than not having the blood test at all? For some, that simple blood test could also indicate that you have aggressive prostate cancer that has spread and needs immediate treatment.

For more information about PSA screening, check out my KQED Quest blog.

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Stem Cells Cause Clogged Arteries

illustration of how the newly discovered vascular stem cells can become smooth muscle, fat, cartilage or bone cells.
Within the walls of blood vessel are smooth muscle cells and newly discovered vascular stem cells. These stem cells are able to differentiate into smooth muscle, fat, cartilage and bone cells. (Song Li illustration)

Odds are that you know someone who’s had a heart attack. If you’re like me, you know many. One American suffers a coronary event every 25 seconds and about every minute someone dies from one.

Doctors thought they understood artery-hardening diseases that lead to heart attacks, strokes and death. But these theories have been contradicted by new research performed at the University of California, Berkeley. According to a new study published in Nature Communications, a previously unknown type of stem cell is actually the underlying cause for clogged arteries.

Researchers analyzed cells from blood vessels of transgenic mice and humans. They were able to trace the lineage of the cells that rapidly reproduced to cause a build up of fibrous scar tissue in the vessel walls. Current theories predicted these would be smooth muscle cells but instead they were a newly discovered type of stem cell.

Specifically they determined that the culprit behind clogged arteries are multipotent vascular stem cells that can develop into various specialized cells – smooth muscle, nerve, cartilage, bone and fat cells. This explains how arteries can calcify and harden, since the stem cells can form bone and cartilage.

If this research is verified in animals and humans by other research groups, this could lead to new therapies.

For more information about this research, check out my KQED Quest blog.

Hope for an anti-Nicotine Vaccine

Photograph courtesy of Ianier67 via Creative Commons.

A friend once told me that it was 100 times harder for him to quit smoking cigarettes than to quit drinking alcohol. He was successful and hasn’t smoked a cigarette for over 10 years, but he’s a lucky minority. I have several other friends who still struggle with smoking cigarettes – willpower, counseling, exercising, nicotine replacement patches and antidepressants like Zyban haven’t been enough.

Clearly nicotine is highly addictive. About 45 million people in the U.S. smoke cigarettes, even though cigarette smoking leads to 1 of every 5 deaths each year. In a National Health Interview Survey, over half of the smokers reported trying to quit in the past year without success.

In the future, these smokers may get a vaccine to help protect them from nicotine addiction.

Researchers from Weill Cornell Medical College and Scripps Research Institute have developed a new vaccine that may treat nicotine addiction, by blocking the pleasurable sensations that nicotine creates in the brain. Dr. Ronald Crystal and his colleagues have demonstrated that they can prevent nicotine from reaching the brain in mice using a single injection of vaccine. If these findings are confirmed in people, this vaccine could be an effective therapy to help prevent nicotine addiction.

For more information about this research, check out my KQED Quest blog.

Screenings Sunscreens

photograph of someone applying sunscreen
Photograph courtesy of Hacklock via Creative Commons.

I’m one of those grocery shoppers who turns the package around to check the ingredients, before I buy it for the first time. Checking food packages is relatively easy, because I expect only recognizable simple ingredients. As they say, would my Great Grandmother recognize this as food? What about sunscreen? How can you tell if it’s safe?

The Environmental Working Group (EWG) has done extensive research to evaluate the effectiveness and safety of over 1800 sunscreens on the market, so you don’t have to. Their sixth annual 2012 Sunscreen Guide lists the best and worst sunscreens. It’s worth a look to make sure your sunscreen isn’t on their “Hall of Shame.” The EWG also provides detailed information about potentially harmful sunscreen ingredients.

For more information about sunscreen safety, check out my KQED Quest blog.

New Research to Conquer Food Allergies

peanuts
Photograph courtesy of Euromagic via Creative Commons.

My nephew is one of the 6 million children in the United States with food allergies. He has a severe nut allergy, requiring an EpiPen (adrenaline) injection and immediate trip to the emergency room after contact with someone whose touched or eaten nuts. His rapid onset of life-threatening symptoms includes swelling of the throat, difficulty breathing, and hives. He isn’t alone. The number of children with peanut allergies has tripled in the last decade. Every three minutes a food allergy reaction sends someone to the emergency room and every 6 minutes the reaction is one of life-threatening anaphylaxis.

However, the 15 million people with food allergies now have hope. New clinical trials show promise for three experimental treatments: oral immunotherapy, sublingual immunotherapy and food allergy herbal formula-2. Scientists are also trying to understand how food allergies develop to help prevent them.

For more information on food allergies, check out my KQED Quest blog.

New Prostate Cancer Treatment Reduces Side Effects

Photograph of the University Hospital London
University College Hospital in London. Courtesy of Steve Parkinson via Creative Commons.

Standard prostate cancer treatments, such as prostatectomy surgery or radiotherapy, often lead to substantial side effects. These include erectile dysfunction (affecting 30-70%) and urinary incontinence (affecting 5-20%). However, these unwanted side effects could be reduced, if prostate cancer treatments could target just the cancer tumors while harming less of their surrounding healthy tissue.

A promising “proof of concept” research study has just demonstrated that a new technique to treat localized prostate cancer may significantly reduce side effects compared to standard treatments. This study was carried out by researchers from University College London and the results were just published in the peer-reviewed medical journal The Lancet Oncology.

This new treatment uses high-intensity focused ultrasound (HIFU) to target and destroy prostate tumors, while causing minimal damage to their surrounding nerves and muscles. A small ultrasound probe is placed close to the prostate through the patient’s rectum. This probe emits a narrow beam of intense sound waves that heat the targeted cells to 80 C for one second, killing a targeted area about the size of a grain of rice. The probe is then moved to focus and destroy additional cancerous areas.  The procedure is performed in the hospital under general anesthesia and most patients are back home within 24 hours.

Surgeon Hashim Ahmed from University College Hospital in London demonstrates in a BBC News short video how this probe heats only a small target area.

The “proof of concept” HIFU study was primarily focused on assessing the frequency and extent of side effects, rather than the success of the prostate cancer treatment. Forty-one men participated in the study, ranging in age from 45 to 80 years old. All participants had localized prostate cancer ranging from low to high risk, where 30 men (73%) had intermediate to high-risk disease. They also had a prostate volume of 40 mL or less in order to avoid an excessively long procedure. They had received no previous prostate treatment.

The prostate cancer tumor locations were identified using multiparametric MRI (magnetic resonance imaging) and a template-prostate-mapping biopsy. The identified tumors were then targeted by the HIFU treatment. The men were followed up at one, three, six, nine and twelve months after the HIFU procedure. Each follow-up included: (1) a PSA blood test to measure the levels of prostate specific antigen protein being produced by the prostate, since PSA is generally elevated for men with prostate cancer; and (2) questionnaires that evaluated side effects. In addition, the MRI and biopsy tests were repeated as part of the 6 months follow-up and an additional MRI was performed after a year.

Researchers found that a year after the HIFU treatment, 89% of the men still had erectile function and all were still continent. In addition, there was a significant decrease in PSA levels compared to baseline and 95% of the men showed no evidence of disease on the final MRI scan.

Clearly this HIFU pilot study has demonstrated a promising reduction in treatment side effects. However, it was a small observational study of 41 men and followed them for only a year. The results need to be confirmed by much larger clinical trials that assess both the effectiveness and safety of HIFU compared with standard therapies. As a result, the researchers at University College London have started recruiting patients for a larger phase 2 trial that will follow patients for 3 years.

Is Your Dentist Giving You A Brain Tumor?

dental x-ray
Courtesy of TheKarenD via Creative Commons.

In the United States, it is common to have dental X-rays as part of your regular checkup or when you have tooth pain. These X-rays use a small amount of ionizing radiation to take a picture of your teeth, bones and gums in order to show tooth decay, impacted teeth, bone loss, and other mouth problems.  Since ionizing radiation exposure is known to increase the risk of certain kinds of cancer, scientists have recently studied whether dental X-rays increase your risk of brain tumors.

An article was just published in the peer-reviewed medical journal, Cancer. It reported the results of a large study that examined the association between dental X-rays and the risk of the most common type of brain tumor (meningioma). The study was headed by researcher Elizabeth Claus, M.D., Ph.D. at the Yale University School of Medicine, in collaboration with the University of California at San Francisco School of Medicine, Brigham and Women’s Hospital, University of Texas M.D. Anderson Cancer Center, and Duke University of Medicine.

Recent news coverage sensationalized the results of this study, possibly alarming people and dissuading them from having dental X-rays. So here are the basics of the report. This research was a case-control study that compared the histories of 1433 people who had a confirmed meningioma brain tumor (the “cases”) with 1350 people without a brain tumor (the “controls”) who were matched to have the same age, sex and state of residence as the brain tumor cases. All participants were 20 to 79 years old, lived in the United States, and were enrolled in the study between May 2006 and April 2011. Both groups were contacted by telephone and interviewed for about an hour. This phone interview included questions about the onset, frequency and type of dental care they had received over their lifetime.

The researchers were interested in three types of dental X-rays:

  • Bitewingsa small X-ray view that shows the upper and lower back teeth simultaneously, where the patient bites down on a small holder filled with the X-ray film. Bitewings are frequently used during regular checkups to look for cavities.
  • Full-mouth – a series of about 14-21 X-ray films that are used to view the entire mouth for dental problems, usually performed during a person’s first visit to the dentist.
  • Panoramic – a single X-ray that shows a broad view of the entire mouth to provide information about the teeth, jawbones, sinuses, and other tissues of the head and neck. Panoramic X-rays are taken occasionally, often to evaluate wisdom teeth, using a machine that moves around the patient’s head.

This large case-control study showed that people with a brain tumor reported having dental X-rays significantly more frequently over their lifetime than the controls without a brain tumor. However, the differences were only significant for bitewing and panoramic type dental X-rays, and not for full-mouth X-rays which actually expose the mouth to a greater dose of radiation. This inconsistency demonstrates that further research is needed to prove any link between dental X-rays and brain tumors.

The biggest issue with this study is that participants were asked to recall their own history of dental X-rays throughout their lifetime, which makes the results less reliable. In particular, there is a fear of “recall bias” – the people with brain tumors may have been focusing on the potential causes of their cancer and therefore may have been more likely to recall dental X-rays than the control group, potentially biasing the results. Although more work, the researchers should have acquired the participants’ dental histories directly from medical records.

While this study does suggest that regular dental X-rays may be linked to an increased risk of developing a brain tumor, it does not prove an actual link. There could be other factors that contributed to this association. In order to establish a causal link, the researchers should consider performing a different kind of study that follows a group of people over time to see who develops a brain tumor.

More importantly, the recent sensationalized news headlines ignored the important fact that brain tumors are rare. Men and women in the United States have a 0.61% lifetime risk of being diagnosed with any type of primary malignant brain or central nervous system tumor, implying a 0.21% lifetime risk of developing meningioma. For instance, this is much smaller than the 12.2% lifetime risk of a woman developing breast cancer.

So this research study should not scare people away from having dental X-rays when recommended by their dentist. The American Dental Association recommends that dentists now evaluate the benefit of X-ray exposure for each patient, reducing the frequency of routine X-rays for healthy patients. In addition, dental X-rays now expose patients to less radiation than in the past.