Men Who Have this Popular PSA Prostate Cancer Screening Have a Staggering 4-Fold Increase in Serious Blood Infections


Men Who Have this Popular PSA Prostate Cancer Screening Have a Staggering 4-Fold Increase in Serious Blood Infections

Story at-a-glance

  • The benefits of PSA prostate cancer screening has been repeatedly shown to be minimal at best and detrimental at worst. Overall, PSA screening barely has any impact on mortality rates from prostate cancer. As a result, the U.S. Preventive Services Task Force will soon recommend that men not get screened for prostate cancer.
  • According to Stanford University researchers, the PSA test indicates nothing more than the size of your prostate gland. . The false positive rate is high, and the bulk of the harm is a result of subsequent unnecessary treatments.
  • Canadian researchers have raised the alarm over prostate biopsies, citing a four-fold increase in serious blood infections over the past decade from the procedure. Researchers are also questioning the conventional treatments of prostate cancer, which include surgical removal of the prostate gland and radiotherapy, as they may not be necessary for most men.
  • Your diet can greatly impact your prostate health and help prevent enlarged prostate and prostate cancer. Ideally, you’ll want to eat as much organic (preferably raw) food as possible, and limit sugar/fructose and grains from your diet. Highly processed or charcoaled meats, pasteurized dairy products, and trans fats correlate with an increased risk for prostate cancer and should also be avoided. Other specific nutritional therapies are discussed.

Prostate cancer is one of the most common cancers in men, but it is not  as deadly as breast cancer.

According to the latest statistics from the American Cancer Society, an estimated 240,890 men will be diagnosed with prostate cancer this year, and just over 33,700 men may die from it, so only one in seven diagnosed with it will die from it.

Overall, American men have a one in six chance of being diagnosed with prostate cancer at some point in their lives, or one in 42 chance of dying from it..

Most cases of prostate cancer do not occur until after men turn 50, but in recent years there has been a steady rise in the percentage of men in their 30s and 40s with both prostate problems and prostate cancer, primarily as a result of poor diet and increasing environmental pollution.

Unfortunately, investigations over the years have discovered serious flaws with the PSA test used to diagnose prostate cancer.

And the U.S. Preventive Services Task Force—which has also declared women in their 40s don’t need mammograms—may soon recommend that men not get screened for prostate cancer using the PSA test.

Researchers are also questioning the conventional treatments of prostate cancer, which include surgical removal of the prostate gland and radiotherapy, as they may not be necessary for most men.

All in all, I think this really highlights the necessity to employ preventive strategies, which I will discuss at the end of this article.

Moderate to High Certainty PSA Test Does More Harm than Good, Task Force Says

The prostate-specific antigen test (PSA test), analyzes your blood for prostate-specific antigen (PSA), a substance produced by your prostate gland.  When higher-than-normal levels of PSA are detected, it is believed that cancer is present.

However, the PSA test has been criticized as useless for a number of years now. For example, back in 2004, Stanford University News reported:

“The most commonly used screening tool for detecting prostate cancer – the PSA test – is virtually worthless for predicting men’s risk of contracting the disease, medical school researchers have determined. Stanford scientists studied prostate tissues collected in the 20 years since a high PSA test result became the standard for prostate removal. They concluded that as a screen, the test indicates nothing more than the size of the prostate gland.”

The U.S. Preventive Services Task Force is now planning on recommending a “D” rating for PSA testing, meaning that “there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”  A review of studies has shown that the PSA blood test yields “small or no reduction” in prostate cancer deaths.

As reported by CNN:

“The report adds that PSA testing is ‘associated with harms related to subsequent evaluation and treatments.’ … The problem is that many of the cancers that get detected are so small and slow-growing, they’ll never be harmful, and doctors have a difficult time discerning the quick, harmful cancers from the slow, harmless ones.”

The PSA Test for Prostate Cancer is Deceptive

Today, many experts agree that PSA testing is unreliable at best and useless at worst for accurately diagnosing prostate cancer. Many also agree that routine PSA blood tests often lead to over-diagnosis of prostate cancer, resulting in unnecessary treatments. Similar to mammograms, the PSA screen has become little more than an up-sell technique. The false positive rate is high, and the bulk of the harm is a result of subsequent unnecessary treatments.

According to the American Cancer Society: “There can be different reasons for an elevated PSA level, including prostate cancer, benign prostate enlargement, inflammation, infection, age, and race,” all factors that make PSA test results confusing, leading to potential for unnecessary treatment and suffering when tests are elevated.  Getting a PSA test reduces your lifetime risk of dying from prostate cancer from three percent to just 2.4 percent, so the difference is negligible.

Drs. Boyle and Brawley of the International Prevention Research Institute, Lyon, France have said,

“The real impact and tragedy of prostate cancer screening is the doubling of the lifetime risk of a diagnosis of prostate cancer with little if any decrease in the risk of dying from this disease.”

Complications of ill advised prostate cancer treatments include urinary incontinence and erectile dysfunction. Both of these conditions are difficult to reverse and can significantly decrease your quality of life.

Prostate Biopsies Can Result in Dangerous Infections

A positive PSA test will typically lead to a biopsy—which has also come under increasing scrutiny and criticism in recent years. On the one hand, the procedure itself may cause acute or long-term harm, and on the other, the rate of false negatives is high.

There are over one million prostate cancer tissue biopsy procedures performed annually in the U.S. Approximately 25 percent of these tissue biopsies are reported “positive,” indicating the presence of prostate cancer. The remaining 75 percent are reported “negative.” One-third of the men with initial “negative” results for prostate cancer actually do have prostate cancer that was missed by the biopsy.

A prostate biopsy involves inserting fine needles into the prostate gland. But specialists have begun to worry about a recent, significant increase in the risk of complications from the procedure. In particular, they are concerned about hard-to-treat bloodstream infections that can require weeks of treatment. Over the past decade, the rate of hospital admissions in Ontario, Canada, for serious infections caused by prostate biopsy increased four-fold.

Earlier this summer, the NPR reported:

“Doctors all over the world are increasingly concerned about post-biopsy infections. At last week’s annual meeting of the American Urological Association, there were 10 reports on the phenomenon … The underlying problem, many say, is the spread of antibiotic-resistant microbes.”

Prostate biopsies inherently pose a risk for infection because:

  • The needles that collect a tiny piece of prostate tissue can transport bacteria through your rectal wall into the prostate and bloodstream, and/or
  • The needles can spread harmful bacteria present in your gut into your bloodstream

Many Cancer Screenings Don’t Save Lives and May Cause Cancer

A recent article featured on PreventDisease.com brings up yet another problem with the PSA test:

“Perhaps most concerning, the PSA test frequently identifies something that qualifies as cancer under a microscope but acts nothing like cancer in real life. That is to say, the large majority of PSA-discovered “cancers” would never cause any problem whatsoever if they went undetected. Finding something through screening invariably leads to treating it through conventional means which cause cancer themselves.”

An underlying issue that needs to be addressed is that both breast- and prostate cancer screenings (mammography and PSA testing respectively) fail to address prevention. Although they are commonly viewed as “preventive” measures, they’re nothing of the sort.  Furthermore, they both appear to result in increased risk of mortality.

The article on PreventDisease.com also includes the following shocking statistics about breast- and prostate cancer screening:

“In a Swedish study of 60,000 women, 70 percent of the mammographically detected tumors weren’t tumors at all. These “false positives” aren’t just financial and emotional strains, they may also lead to many unnecessary and invasive biopsies. In fact, 70 to 80 percent of all positive mammograms do not, upon biopsy, show any presence of cancer.

When it comes to prostate cancer, a 20-year study from Sweden suggests that screening for prostate cancer does not reduce the risk of death from the disease. In fact, many men receive false-positive results and overtreatment, adding an element of risk to widescale screening, researchers report in the March 31 online issue of the BMJ.

“In the light of our findings, I would say that the benefit from screening is not sufficient to support mass screening,” said study author Dr. Gabriel Sandblom, an associate professor at the Karolinska Institute in Stockholm.”

http://www.afcomponents.com/flv/swf/flv_demo.swf

Screens and Treatments Involving Radiation Promote Cancer

Cancer screens like mammography and radiation treatment of either breast- or prostate cancer are not benign tests and treatments. It’s important to understand that radiation exposure causes genetic mutations in cells, and is also known to switch off a tumor suppressing gene. According to PreventDisease.com:

“[N]ew research from the Lawrence Berkeley National Laboratory in America (a US Government facility) has shown that radiation both changes the environment around breast cells, and increases the risks of mutation within them; a mutation that can be passed on in cell division. Four to six weeks after exposure to radiation at a level below that of a screening mammogram, breast cells started to prematurely age.

This results in their inability to send certain chemical messages into their immediate environment, which then filled with pre-cancerous mutated cells also from the radiation.

Paul Yaswen, a cell biologist and breast cancer research specialist with Berkeley Lab’s Life Sciences Division says “our work shows that radiation can change the microenvironment of breast cells, and this in turn can allow the growth of abnormal cells with a long-lived phenotype that have a much greater potential to be cancerous.”

Yawsen stated that radiation specialists have been slow in understanding these concepts. “Many in the cancer research community, especially radiobiologists, have been slow to acknowledge and incorporate in their work the idea that cells in human tissues are not independent entities, but are highly communicative with each other and with their microenvironment.”

Despite the Evidence, Many Cling to the PSA Test

Shannon Brownlee, author of Overtreated, recently wrote an insightful article for Time Magazine on this topic as well.  Many men are responding with outrage at the news that the PSA test will no longer be recommended. Many prostate cancer survivors credit the PSA test with saving their lives.

“The trouble is most men who get treated didn’t have a cancer that needed treating,” Brownlee writes. “So while a given man may believe fervently that early treatment saved his life, there’s a better than even chance that he would have been fine even if his cancer had been left well enough alone.

We never hear from the men who died from their prostate cancer treatment or biopsy. And there have been plenty of them. The mortality rate during or shortly after prostate surgery is estimated to be 1 in 200, according to a study published in the Journal of the National Cancer Institute. We also don’t hear much from the men who are suffering from incontinence, impotence, or both, the devastatingly common side effects of treatment.”

This is probably to be expected. If it was you, how willing would you be to tell the world that you’re now incontinent and impotent as a result of opting to get tested for prostate cancer? These are personal details that few men are willing to share.

How to Maintain Optimal Prostate Function and Help Prevent Prostate Cancer

Men over 70 have a 50/50 chance of developing an enlarged prostate, known as benign prostate hyperplasia (BPH). This is not the equivalent of prostate cancer. However, you do need to address this issue, and unfortunately, the conventional route includes drugs. It’s important to know that some of these drugs actually carry a warning label that if you have benign prostate hyperplasia, the drug may increase your cancer risk, and/or may promote a much more aggressive form of cancer.

For more information about this, please review this previous article on prostate health, which includes an informative interview with Dr. Rudi Moerck. Diet is a factor that can greatly impact your prostate health and help prevent enlarged prostate and prostate cancer.

You’ll want to eat as much organic (preferably raw) food as possible, and liberally include fresh herbs and spices, such as ginger. Make sure to limit carbohydrates like sugar/fructose and grains as much as possible to maintain optimal insulin levels, which will help reduce your cancer risk in general. Highly processed or charcoaled meats, pasteurized dairy products, and trans fats correlate with an increased risk for prostate cancer and should also be avoided.

There are also a number of more specific nutritional therapies that are particularly beneficial for avoiding and/or treating prostate cancer.

  • Include prostate-healthy foods in your daily diet: Foods that support prostate health include vegetables and fruits rich in antioxidants, vitamins, cartenoids like astaxanthin, and lycopene. One 2009 study identified tomatoes, cauliflower, broccoli and green tea as being particularly beneficial against prostate cancer
  • Try saw palmetto: The medical literature contains about 100 clinical studies on saw palmetto for prostate health and reduced incidence of prostate cancer. Trying saw palmetto before you resort to a drug is well worth it, considering the stern warnings that accompany some of these drugs. According to Dr. Moerck, saw palmetto in combination with pumpkin seed or lycopene may be an even more potent combination.

    Beware that quality is very important when selecting a saw palmetto supplement. Most brands on the market are ineffectual because they use the inactive form of the plant.

    The highest quality products are the organic supercritical-extracted saw palmetto oils, which are very dark green in color. Only one or two out of every 20 brands will be of this high quality. Dr. Moerck recommends a daily dose of 320 mg of saw palmetto oil (supercritical CO2 extract). Keep in mind that saw palmetto is a fat soluble supplement, so it will not absorb well unless you take it in conjunction with a little bit of fat. I recommend taking it with eggs, which contain phospholipids that enhance absorption of fat soluble nutrients.

  • Optimize your vitamin D levels, ideally by exposing your bare skin to natural sun light on a regular basis. (Your skin also synthesizes vitamin D sulfate, which may account for many of vitamin D’s potent health benefits, so sun exposure is really the ideal way to optimize your levels and get the greatest overall health benefits.) Evidence suggests that vitamin D may be one of the most potent variables associated with a lower risk of prostate cancer.

    There are well over 800 scientific studies confirming the link between vitamin D deficiency and multiple types of cancers, including prostate cancer. For example, according to a 2005 study, men with higher levels of vitamin D in their blood were half as likely to develop aggressive forms of prostate cancer as those with lower amounts. Another study published two years ago found that men with higher levels of vitamin D in their blood were seven times less likely to die from prostate cancer than those with lower amounts.

    Testing your vitamin D levels is done by a simple blood test. Anything below 20 ng/ml is considered a serious deficiency state, which will increase your risk of breast- and prostate cancers.

    The optimal value that you’re looking for is between 50-70 ng/ml. However, research has suggested that maintaining a slightly higher level of 70-100 ng/ml may be optimal for cancer prevention. If you can’t get regular sun exposure, you may want to consider using a safe tanning bed (one that uses electronic rather than magnetic ballasts and has less, not more, UVA than the sun produces). If these are unavaialble you can opt for an oral vitamin D3 supplement. Keep in mind that when using a supplement, regular testing becomes even more important to make sure you’re staying within therapeutic range.

  • Consider a vitamin K2 supplement: Another nutrient that has been found to offer significant protection against prostate cancer is vitamin K2. For more information about that, please refer to this previous article. Although I don’t typically recommend taking a lot of supplements, vitamin K is one you may want to seriously consider because many people don’t get nearly enough of it on a daily basis through the foods they eat.
  • Exercise your body, and your prostate: Having a well-rounded exercise regimen is essential for overall health, and is now becoming more widely accepted as a critical piece of cancer prevention and treatment. Having sex on a regular basis, which exercises your prostate specifically, is also important.
  • Check your testosterone levels: Contrary to popular belief, restoring testosterone levels in aging men does not appear to promote prostate cancer—on the contrary! According to meticulous research by Dr. Abraham Morgentaler, MD, author of Testosterone for Life, men with low testosterone are the ones at greater risk. For an interesting article that contains a lot more information about this, read Dr. Morgentaler’s report Destroying the Myth About Testosterone Replacement and Prostate Cancer.

    It explains how unfortunate assumptions have led to a dogmatic belief that testosterone replacement increases your risk of prostate cancer—a belief that might now be preventing many men from being optimally healthy. If you are low you can consider trans rectal DHEA cream. I personally use about 50 mg twice a day, and it has done wonders to optimize my testosterone levels as DHEA is converted to testosterone in your body.

Ideally, you’ll want to pay close attention to your prostate health early on—avoid waiting until you’re in your 60’s. Incorporating the lifestyle recommendations discussed above can help you prevent prostate problems from developing in the first place.

Source:mercola.com

PSA for the Prediction of Clinical Progression After Radical Prostatectomy


TAKE-HOME MESSAGE

New catalyst yields more accurate PSA test: Peroxidase mimic improves sensitivity of PSA test 100-fold .


Chemists have developed a catalyst that improves the sensitivity of the standard PSA test over 100-fold. The catalyst is made of palladium nanocubes coated with iridium.

A new catalyst that improves the sensitivity of the standard PSA test more than 100-fold, pictured above, is made of palladium nanocubes coated with iridium.

Say you’ve been diagnosed with prostate cancer, the second-leading cause of cancer death in men. You opt for surgery to remove your prostate. Three months later, a prostate surface antigen (PSA) test shows no prostate cells in your body. Everyone rejoices.

Until 18 months later, when another PSA test reveals that now prostate cells have reappeared. What happened?

The first PSA test yielded what’s known as a false negative result. It did not detect the handful of cells that remained after surgery and later multiplied. Now a chemist at Michigan Technological University has made a discovery that could, among other things, slash the numbers of false negatives in PSA tests.

Xiaohu Xia and his team, including researchers from Louisiana State University and the University of Texas at Dallas, have developed a new catalyst that could make lab tests like the PSA much more sensitive. And it may even speed up reactions that neutralize toxic industrial chemicals before they enter lakes and streams.

A paper on the research, “Pd-Ir Core-Shell Nanocubes: A Type of Highly Efficient and Versatile Peroxidase Mimic,” was published online Sept. 3 inACS Nano. In addition to Xia, the coauthors are graduate students Jingtuo Zhang, Jiabin Liu and Haihang Ye and undergraduate Erin McKenzie of Michigan Tech; Moon J. Kim and Ning Lu of the University of Texas at Dallas; and Ye Xu and Kushal Ghale of Louisiana State University. The LSU team conducted theoretical calculations, and the UT Dallas team contributed high-resolution electron microscopy images.

Their new catalyst mimics the action of similar biochemicals found in nature, called peroxidases. “In animals and plants, these peroxidases are important– for example, they get rid of hydrogen peroxide, which is harmful to the organism,” said Xia, an assistant professor of chemistry at Michigan Tech. In medicine, peroxidases have become powerful tools for accelerating chemical reactions in diagnostic tests; a peroxidase found in the horseradish root is commonly used in the standard PSA test.

However, these natural peroxidases have drawbacks. They can be difficult to extract and purify. “And, they are made of protein, which isn’t very stable,” Xia explained. “At high temperatures, they cook, like meat.”

“Moreover, their efficiency is just fair,” he added. “We wanted to develop a mimic peroxidase that was substantially more efficient than the natural peroxidase, which would lead to a more-sensitive PSA test.”

Their new catalyst, made from nanoscale cubes of palladium coated with a few layers of iridium atoms, does just that. PSA tests Xia’s team conducted using the palladium-iridium catalyst were 110 times more sensitive than tests completed with the conventional peroxidase.

“After surgery, it’s vital to detect a tiny amount of prostate antigen, because otherwise you can get a false negative and perhaps delay treatment for cancer,” said Xia. “Our ultimate goal is to further refine our system for use in clinical diagnostic laboratories.”

Xia hopes that his mimic peroxidase will someday save lives through earlier detection of cancer and other maladies. He also plans to explore other applications, including how it compares with horseradish peroxidase in other catalytic reactions: breaking down toxic industrial-waste products like phenols into harmless substances.

Finally, the team wants to better understand why its palladium-iridium catalyst works so well. “We know the iridium coating is the key,” Xia said. “We think it makes the surface sticky, so the chemical reagents bind to it better.”

Seminal vesicle carcinoma.


A 56-year-old man presented with a 29 day history of urgency and twice-hourly micturition. Physical examination was shown a cystic mass in the lower left abdomen. Intravenous urography showed right kidney hydronephrosis and hydroureter. CT scan of the pelvis showed a cystic mass behind the bladder, measuring 14·6 × 10·6 × 12·0 cm . Three-dimensional reconstruction of the pelvis showed a seminal vesicle adenocarcinoma (and the extruded and displaced bladder).

semvcyst

Prostate specifc antigen (PSA) before admission was 40·75 ng/mL. On admission, he was clinically stable, with serum PSA concentration of 28 ng/mL. Urine cytology examination measured three times was negative. Our presumptive diagnosis based on imaging results was a seminal vesicle diverticulum. No bladder tumours were found on cystoscopy and our patient had bilateral ureteral intubation and laparoscopic resection of the pelvic mass. Histopathological examination showed seminal vesicle papillary adenocarcinoma. Immunohistochemical staining was positive for CEA and CK7, negative for CA125, PSA and PsAP. Postoperative histologic examination confirmed the diagnosis of primary papillary adenocarcinoma of the seminal vesicle.

Source: Lancet

Urological Group’s Guidelines Recommend Against PSA Screening in Most Men.


The American Urological Association‘s new guidelines recommend prostate cancer screening only in men aged 55 to 69 and based on shared decision-making and the patient’s preferences. The guidelines put AUA‘s position more in line with other medical organizations.

In the 55-to-69 age group, one prostate-cancer death is prevented for every 1000 men screened over a decade. For men who decide to undergo prostate-specific antigen screening, AUA recommends testing every two years or more, rather than annual testing.

The group now recommends against routine PSA screening for men younger than 55 who are at average risk, those older than 69, and those with less than 10 to 15 years of expected life remaining.

The recommendations come less than a year after the U.S. Preventive Services Task Force recommended against routine PSA screening in all men.

Source:American Urological Association guidelines

Focused PSA Screening Strategy, Based on Empirical Data.


Three lifetime prostate-specific antigen tests (age: mid 40s, early 50s, and 60) are sufficient for at least half of men.

 

Swedish investigators have reported that 60-year-old men with blood prostate-specific antigen (PSA) levels 1 µg/L have 0.2% risk for prostate cancer within 25 years (JW Gen Med Oct 7 2010). In this study, the same investigators determined the associations between PSA levels at various ages and subsequent risk for metastatic prostate cancer and prostate cancer–related death.

From 1974 to 1984, 21,000 men (age, 52) provided baseline blood samples; 4900 provided additional samples 6 years later. During a median follow-up of 27 years, prostate cancer was diagnosed in 1369 men: Metastatic disease occurred in 241 men, and 163 prostate cancer–related deaths were recorded. Outcomes were as follows:

  • 15-year risk for metastatic prostate cancer was 0.6% for men in the highest PSA decile at age 40 (1.3 µg/L), 1.6% for men in the highest PSA deciles at ages 45 to 49 (1.6 µg/L), and 5.2% for men in the highest deciles at ages 51 to 55 (2.4 µg/L)
  • For men with PSA levels below the median at ages 45 to 49 (0.68 µg/L) and 51 to 55 (0.85 µg/L), 15-year risks for metastatic prostate cancer were only 0.1% and 0.3%, respectively
  • 44% of prostate cancer–related deaths within 30 years occurred in men in the highest PSA deciles at ages 45 to 49 (1.6 µg/L) and 51 to 55 (2.4 µg/L)

Comment: Based on these results, the authors recommend that screening not begin until age 45 and that men with PSA levels 1.0 µg/L undergo one repeat screening in their 50s and one at age 60 (those with PSA levels 1.0 µg/L at age 60 should not undergo further screening). They also suggest that men with PSA levels >1.0 µg/L at any age undergo more frequent screening and that men in the highest PSA deciles at ages 45 to 55 receive “particular focus,” because they contribute close to half of all deaths from prostate cancer before age 75. Although this strategy could be more efficient than the annual screening often conducted in the U.S., whether screening in this manner would prevent prostate cancer–related mortality is unclear.

 

Source:Journal Watch General Medicine

 

Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study.


Abstract

Objective To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified.

Design Case-control study with 1:3 matching nested within a highly representative population based cohort study.

Setting Malmö Preventive Project, Sweden.

Participants 21 277 Swedish men aged 27-52 (74% of the eligible population) who provided blood at baseline in 1974-84, and 4922 men invited to provide a second sample six years later. Rates of PSA testing remained extremely low during median follow-up of 27 years.

Main outcome measures Metastasis or death from prostate cancer ascertained by review of case notes.

Results Risk of death from prostate cancer was associated with baseline PSA: 44% (95% confidence interval 34% to 53%) of deaths occurred in men with a PSA concentration in the highest 10th of the distribution of concentrations at age 45-49 (≥1.6 µg/L), with a similar proportion for the highest 10th at age 51-55 (≥2.4 µg/L: 44%, 32% to 56%). Although a 25-30 year risk of prostate cancer metastasis could not be ruled out by concentrations below the median at age 45-49 (0.68 µg/L) or 51-55 (0.85 µg/L), the 15 year risk remained low at 0.09% (0.03% to 0.23%) at age 45-49 and 0.28% (0.11% to 0.66%) at age 51-55, suggesting that longer intervals between screening would be appropriate in this group.

Conclusion Measurement of PSA concentration in early midlife can identify a small group of men at increased risk of prostate cancer metastasis several decades later. Careful surveillance is warranted in these men. Given existing data on the risk of death by PSA concentration at age 60, these results suggest that three lifetime PSA tests (mid to late 40s, early 50s, and 60) are probably sufficient for at least half of men.

Discussion

Overview of findings

PSA concentration can be used to predict of long term risk of metastasis or death from prostate cancer. It can identify a small group of men at greatly increased risk compared with a much larger group highly unlikely to develop prostate cancer morbidity if rescreening is delayed for seven or eight years. As PSA screening was extremely rare in this cohort, our findings can be used to design screening programmes by determining the age at which men should start to undergo screening and the interval between screenings. Men at low risk of death from prostate cancer without screening have little to gain from being screened but still risk overdiagnosis and overtreatment; men likely to die from prostate cancer without screening could avoid cancer specific mortality if they choose to be screened.

In an earlier paper, we showed that PSA concentration at age 60 had a strong association with the risk of death from prostate cancer by age 85 (AUC 0.90),7 with extremely low risk (≤0.2%) in men with PSA concentration below the median (≤1.0 µg/L). Taken together with our current data, this suggests a simple algorithm for prostate screening. All men with a reasonable life expectancy could be invited for PSA screening in their mid to late 40s. Men with a PSA concentration <1.0 µg/L would be advised to return for screening in their early 50s and then again at age 60, whereas men with PSA ≥1.0 µg/L would return for more frequent screening, with literature suggesting repeat tests every two or four years.19 The choice of 1.0 µg/L as a tentative threshold might vary according to preference. At age 60, men with PSA at median or lower—that is, ≤1.0 µg/L (or possibly below the highest quarter, ≤2.0 µg/L, depending on preference)—would then be exempted from further screening; men with a higher concentration would continue to undergo screening until around 70.1 Particular focus should be placed on men in the highest 10% of PSA concentrations at age 45-55, who will contribute close to half of all deaths from prostate cancer occurring before the age of 70-75. Some of these men will have concentrations above current thresholds for consideration of biopsy—such as 3 µg/L—and should be referred to a urologist. The remaining men could be told that, although they will probably not die from prostate cancer (with a mean risk of metastasis within 25 years close to 10%), they are at much higher risk than average and that it is especially important that they return for regular, frequent, and possibly more elaborate screening. It is also worth considering whether management of these men should become proactive, with reminder letters and attempts to follow-up non-compliers by telephone. Most importantly, the proposed PSA concentration of 1.0 µg/L to discriminate a low from a higher risk group is not suggested to serve as an indication for biopsy but rather be used to determine the frequency and intensity of subsequent monitoring.

What is known on this topic

  • Prostate specific antigen screening is widely used for the early detection of prostate cancer but remains highly controversial.
  • Focusing on the men at highest risk of prostate cancer metastasis and death could improve the ratio between benefits and harms of screening.
  • It is difficult to justify initiating PSA screening at 40 for men with no other significant risk factor
  • Men with PSA in highest 10th at age 45-49 contribute nearly half of prostate cancer deaths over the next 25-30 years
  • At least half of all men can be identified as being at low risk, and probably need no more than three PSA tests lifetime (mid to late 40s, early 50s, and 60)

What this study adds

Source: BMJ

 

 

 

 

 

 

Phase II study of first-line sagopilone plus prednisone in patients with castration-resistant prostate cancer: a phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium.


Preclinical studies in prostate cancer (PC) models demonstrated the anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is the first study to investigate the activity and safety of sagopilone in patients with metastatic castration-resistant PC (CRPC).

Methods:

Chemotherapy-naïve patients with metastatic CRPC received sagopilone (one cycle: 16 mg m−2 intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary efficacy evaluation was prostate-specific antigen (PSA) response rate (50% PSA reduction confirmed 28 days apart). According to the Simon two-stage design, 3 PSA responders were necessary within the first 13 evaluable patients for recruitment to continue until 46 evaluable patients were available.

Results:

In all, 53 patients received 2 study medication cycles, with high compliance. Mean individual dose was 15.1±1.4 mg m−2 during initial six cycles, mean dose intensity 94±9%. The confirmed PSA response rate was 37%. Median overall progression-free survival was 6.4 months. The most commonly reported adverse events (>10% of patients) were peripheral neuropathy (94.3%), fatigue (54.7%) and pain in the extremities (47.2%). Sagopilone was associated with very little haematological toxicity.

Conclusion:

This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-naïve CRPC.

Source: British journal of oncology

 

 

PSA Screening and Quality of Life.


Using simulation modeling, researchers estimated potential gains in quality-adjusted life-years from prostate-specific antigen screening.

Prostate-specific antigen (PSA) screening involves a tradeoff between potential mortality benefit and harms of overdiagnosis. In the European Randomized Study of Screening for Prostate Cancer (ERSPC), PSA screening lowered prostate cancer–related mortality at 11 years, but many men underwent surgery or radiation therapy for every death averted. Thus, researchers concluded previously that more analysis was needed “before general [screening] recommendations can be made” (JW Gen Med Mar 14 2012). Now, they present results of simulation modeling in which they integrated (1) ERSPC mortality outcomes, (2) probabilities of adverse diagnosis-related and treatment-related complications (e.g., incontinence, impotence), and (3) estimates of decrements in quality of life resulting from these adverse outcomes.

The model predicted that screening 1000 men (age range, 55–69) annually would extend the lives of 9 men for an average of 8 years each, adding about 73 life-years overall. However, when adverse effects on quality of life (experienced by all screened men who undergo biopsy and treatment) were factored into the model, the benefit of screening dropped from 73 nonadjusted life-years gained to 56 quality-adjusted life-years (QALYs) gained per 1000 men.

The authors then varied their estimates of adverse effects. Under the most favorable estimates, screening would add 97 QALYs per 1000 men; under the least favorable estimates, screening would result in 21 QALYs lost (meaning that screening would be harmful, on average).

Comment: This report reminds us that, at the population level, the value of PSA screening depends substantially on how men weigh the downstream benefits and harms of screening. One puzzling aspect of this theoretical analysis is its conclusion that screening would prevent 9 prostate cancer–related deaths per 1000 men; this benefit is ninefold larger than what actually has been demonstrated thus far in the ERSPC (1 death prevented per 1000 men screened, after mean follow-up of 11 years). Because this model assumes annual screening starting at age 55 and lifetime follow-up (whereas the ERSPC screened only every 4 years and started screening at various ages), the model’s larger mortality benefit is plausible. However, the huge difference between the estimated benefit and actual ERSPC results is surprising. The authors indirectly acknowledge this issue in their cautious conclusion: “Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made.”

Source: Journal Watch General Medicine

Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer.


Findings of a recent study, the largest and longest of its kind, provide strong evidence supporting a conservative approach to managing prostate cancer in some men. The study was not a randomized clinical trial; rather, it was a long-term analysis of a cohort of men diagnosed with what is called very-low-risk prostate cancer. Instead of immediately undergoing surgery or radiation therapy, the men had opted to undergo a process known as active surveillance at the Johns Hopkins University School of Medicine.

A diagnosis of very-low-risk prostate cancer means that the disease is highly unlikely to become a clinically significant, life-threatening cancer. These men could be safely monitored by active surveillance, the study found, with only a modest percentage eventually requiring some form of treatment and none dying from prostate cancer. The results were published online April 4 in the Journal of Clinical Oncology (JCO).

As is the case with prostate cancer in general in the United States, most of the men in the study were 65 or older. The results provide very strong evidence that active surveillance is the “preferred option” for most men in this age group with very-low-risk disease, said the study’s senior investigator, Dr. H. Ballentine Carter. In fact, he continued, “The overwhelming evidence says that for men over 65 who are diagnosed with low-risk disease, their first question should be whether any therapy is appropriate for them, not which therapy.”

The clinical relevance of the findings is hard to overstate, Dr. Carter stressed. Among the 217,000 men in the United States diagnosed each year with prostate cancer, a substantial proportion has very-low-risk or low-risk disease. The vast majority of these men immediately undergo some form of treatment, including men aged 75 and over, despite the fact that many would be unlikely to experience significant symptoms, let alone die from prostate cancer.

Defining Very-Low-Risk Prostate Cancer

The Johns Hopkins definition of very-low-risk prostate cancer is similar to the NCCN definition. For the study in JCO, very-low-risk was defined as:

  • Clinical stage T1c (no palpable disease, biopsy recommended based on abnormal PSA)
  • Gleason score of 6 or less
  • PSA density (ratio of PSA level to prostate gland size) of 0.15 ng/mL or less
  • Two or fewer biopsy cores in which cancer is present, and less than 50 percent cancer present in any involved core

Patient Selection, Compliance Are Key

At Hopkins, the active surveillance program involves a semi-annual check-up and an annual biopsy. Patient selection is very important, Dr. Carter explained.

Among the 769 men enrolled in Hopkins’ active surveillance program between 1995 and 2010, approximately 80 percent had very-low-risk disease. Whether a patient has very-low-risk disease is determined based on factors such as the Gleason score (a common measure of tumor aggressiveness) and the extent of cancer in the biopsy samples, or cores, from the prostate gland. (See the sidebar for all of the factors.)

The remaining men had at least one biopsy feature that precluded their disease from being considered very-low-risk, Dr. Carter explained. These men were typically older and had other health problems, he continued, which made active surveillance more attractive than treatment with surgery or radiation, both of which can have significant side effects.

Compliance with the approach has been quite strong, the Hopkins team reported, with nearly 90 percent of participants completing their annual biopsies.

Although no men in the study died of prostate cancer, 255 did undergo some form of treatment, 74 percent of whom did so because their disease was reclassified based on the findings of an annual biopsy.

Overall, 41 percent of men in the study did not require any form of treatment, even after 10 years of follow-up, a “remarkable” finding, said Dr. Bhupinder Mann from NCI’s Division of Cancer Treatment and Diagnosis. “This study adds to the accumulating evidence that, in carefully selected patients, active surveillance is safe.”

The results “strongly support” recent revisions to prostate cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN), said the guidelines’ panel chair, Dr. James Mohler from the Roswell Park Cancer Institute. Updated last year, the guidelines recommend that physicians advise men with very-low-risk disease who have a life expectancy of up to 20 years to pursue active surveillance.

Findings like these on active surveillance, combined with related research on the growing problem of overdiagnosis and overtreatment of prostate cancer linked to PSA screening, appear to be reaching down into the community setting, Dr. Mohler believes.

“I think men and their doctors are becoming more educated about the overtreatment issue,” he said.

As evidence, Dr. Mohler pointed to the START trial, a phase III clinical trial being led by NCI-Canada, in collaboration with the U.S. NCI, in which men diagnosed with very-low-risk or low-risk disease are being randomly assigned to active surveillance or immediate treatment. When the trial opened in 2007, most men who declined to enroll did so because they did not want to take the risk of being assigned to the active surveillance arm. “Now most men are declining to participate because they want active surveillance,” Dr. Mohler said.

Having a strong system in place to ensure that men pursuing active surveillance are followed and receive reminders for their check-ups and biopsies is extremely important, Dr. Carter stressed.

At the moment, the Hopkins surveillance program is managed primarily by an administrator using a manual process. But the program is moving to a Web-based approach for monitoring and following patients, he added.

Approaches Can Vary

Although the evidence in favor of active surveillance continues to accumulate, the optimal approach to managing the process is not yet defined, Dr. Mann noted. This is particularly true with respect to how patients’ disease is tracked.

At Hopkins, men are followed via check-ups and annual biopsies. Any reclassification of their disease is typically based on biopsy findings, such as a change in Gleason score, which might then produce a recommendation for treatment. But many other centers, such as Roswell Park, do not require men who choose active surveillance to undergo regular biopsies. Rather, they use some form of what is commonly called PSA kinetics, which are changes in PSA levels over time (for instance, how long it takes for PSA levels to double).

Results from several studies, however, have raised doubts about the value of PSA kinetics in initially identifying or managing prostate cancer. Based on their experience, PSA kinetics is “not reliable for predicting the presence of high-grade cancer on an individual basis,” the Hopkins team wrote in JCO. “Thus, if the goal of surveillance is to identify and treat higher-risk cancers, we believe that annual biopsies may be necessary to ensure patient safety.”

But regular biopsies are by no means without their own risks. A small percentage of men end up in the hospital with antibiotic resistant infections as a result of a prostate biopsy, Dr. Mohler said, and repeat biopsies can lead to inflammation and scar tissue formation that can preclude nerve-sparing surgery to treat the prostate cancer in some men whose disease progresses.

According to Dr. Carter, Hopkins researchers are now studying whether men who have had two consecutive biopsies that show no evidence of disease progression can safely have the interval between routine biopsies extended. In the meantime, the NCCN guidelines are being revised again, Dr. Mohler said, using data from large active surveillance programs at Hopkins, the University of Toronto, and the University of California, San Francisco, to provide recommendations on managing men who choose this conservative approach.

Further clarity on this matter should be forthcoming, Dr. Mann said. In addition to the START trial, which will follow men using both PSA measures and prostate core biopsies, a similar trial is being conducted in the United Kingdom that is using only PSA levels to monitor patients. Also, in December, NCI and CDC are sponsoring an NIH State-of-the-Science Conference to review the role of active surveillance in managing localized prostate cancer and to help guide future research in this area.

Source: NCI.