Users of smokeless tobacco product were found to have higher risk of death from prostate cancer

According to a new study, snus, a smokeless tobacco product, may increase a prostate cancer patient’s risk of death.

Some have suggested that because it lacks the combustive effects of smoking, that snus is a less a harmful alternative to smoking.

However, researchers found the men who used snus and had prostate cancer were at increased risk of premature death.

Pronounced as though it rhymes with “goose”, snus is used mainly in Sweden but is also available in the United States. Sold most often in a bag resembling a tea bag, users place the powdered tobacco product under the upper lip for extended periods.

The researchers investigating snus users, found that, compared with men who never used tobacco, those non-smokers who used snus had a 24 percent higher risk of death from prostate cancer during the study period. They also had a 19 percent higher risk of death from any cause.

The study found that for those non-smokers who used snus whose cancer had not spread; these patients were three times more likely to die from prostate cancer than those who never used tobacco.

The study co-author concluded that there is some evidence from animal studies that nicotine can promote cancer progression, and snus users have high blood levels of nicotine. Although snus is a smokeless product, users are still exposed to other carcinogens in tobacco.

The results of the study suggest that the health effects of smokeless tobacco products can be detrimental to men diagnosed with prostate cancer.

Second opinions for prostate cancer; a study on motivations

A recently-published analysis indicates that many men with prostate cancer obtain second opinions from urologists before starting treatment. Surprisingly though, second opinions are not associated with changes in treatment choice or improvements in perceived quality of prostate cancer care. This analysis also explores motivations for seeking second opinions, and suggests that second opinions may not reduce overtreatment in prostate cancer.

Cancer societies encourage patients with cancer to obtain second opinions prior to starting treatment to help them understand their disease and to thoroughly weigh the risks and benefits of their options. Given the ongoing debate concerning whether prostate cancer patients are being overtreated, second opinions in this context are important because management options vary widely from surgery and radiation therapy to active surveillance programs. However, the study did not find that second opinions affected treatment among low-risk men – the most likely candidates for active surveillance – casting doubt on whether second opinions are sufficient to reduce overtreatment among this group.

A physician at Johns Hopkins University and a team of colleagues sought to assess the frequency of and reasons for second opinions for localized prostate cancer, and the characteristics of those who seek them. They also evaluated whether second opinions are associated with certain treatment choices or perceived quality of prostate cancer care.

The investigators surveyed men as part of the Philadelphia Area Prostate Cancer Access Study. A total of 2386 men who were newly diagnosed with localized prostate cancer in the greater Philadelphia area between 2012 and 2014 responded. Forty percent of men obtained second opinions, commonly because they wanted more information about their cancer (50.8 percent) and wanted to be seen by the best doctor (46.3 percent). Overall, obtaining second opinions was not linked with receiving definitive treatment or with perceived quality of cancer care.

Men who sought second opinions because they were dissatisfied with their initial urologist were 51 percent less likely to receive definitive treatment, and men who wanted more information about treatment were 30 percent less likely to report excellent quality of cancer care compared with men who did not receive a second opinion. Men who obtained second opinions because they wanted more information, were seeking the best doctor, or had been encouraged to by family or friends were more likely to ultimately receive surgery. The analysis suggests this could indicate that for some men, second opinions represent a way to pursue the treatment they already plan on receiving, rather than to explore other treatment options.

Some quick facts regarding prostate cancer

Here are some important facts about prostate cancer.
• After non-melanoma skin cancer, prostate cancer is the most common cancer among men in the US.
• Prostate cancer is one of the leading causes of cancer death among men of all races and Hispanic origin populations.
• In the US around 209,292 men are diagnosed with prostate cancer per year.
• Around 27,970 men die from prostate cancer in the US each year.
• According to the American Cancer Society about 1 man in 7 will be diagnosed with prostate cancer during his lifetime.
• Prostate cancer mainly occurs in older men – about 6 cases in 10 are diagnosed in men 65 years or older.
• Almost all prostate cancers are adenocarcinomas – cancers that begin in cells that make and release mucus and other fluids.
• Prostate cancer often has no early symptoms.
• Advanced prostate cancer can cause men to urinate more often or have a weaker flow of urine.
• Most men diagnosed with prostate cancer do not die from it. More than 2.9 million men in the US diagnosed with prostate cancer at some point are still alive today.

Possible benefits of nutrition and lifestyle changes to help treat prostate cancer

Many studies have looked at the possible benefits of specific nutrients (often as supplements) in helping to treat prostate cancer, although most of this research is still ongoing.

Some compounds being studied include extracts from:
Green tea
Flax seed

Some early research has found that in men with a rising PSA level after surgery or radiation therapy, drinking pomegranate juice or taking a pomegranate extract may slow the time it takes for the PSA level to double. Larger studies are now looking for possible effects of pomegranate juices and extracts on prostate cancer growth.

Some encouraging early results have also been reported with flax seed supplements. One small study in men with early prostate cancer found that daily flax seed seemed to slow the rate at which prostate cancer cells multiplied. More research is needed to confirm this finding.

A recent study showed that taking soy supplements after surgery (radical prostatectomy) for prostate cancer did not lower the risk of the cancer coming back.

One study has found that men who choose not to have treatment for their localized prostate cancer may be able to slow its growth with intensive lifestyle changes. The men in the study ate a vegan diet (no meat, fish, eggs, or dairy products) and exercised frequently. They also took part in support groups and yoga. After one year the men saw, on average, a slight drop in their PSA level. It isn’t known if this effect will last since the report only followed the men for 1 year. The regimen may also be hard for some men to follow.

Early detection methods for prostate cancer

Doctors agree that the prostate-specific antigen (PSA) blood test is not a perfect test for finding prostate cancer early. It misses some cancers, and in other cases the PSA level is high even when prostate cancer can’t be found. Researchers are working on strategies to address this problem.

One approach is to try to improve on the test that measures the total PSA level.

Another approach is to develop new tests based on other forms of PSA, or other tumor markers. Several newer tests seem to be more accurate than the PSA test, including:

The phi, which combines the results of total PSA, free PSA, and proPSA to help determine how likely it is that a man has prostate cancer that might need treatment

The 4Kscore test, which combines the results of total PSA, free PSA, intact PSA, and human kallikrein 2 (hK2), along with some other factors, to help determine how likely a man is to have prostate cancer that might need treatment

Tests such as Progensa that look at the level of prostate cancer antigen 3 (PCA3) in the urine after a digital rectal exam (DRE). (The DRE pushes some of the prostate cells into the urine.) The higher the level, the more likely that prostate cancer is present.

Tests that look for an abnormal gene change called TMPRSS2:ERG in prostate cells in urine collected after a DRE. This gene change is found in some prostate cancers, but it is rarely found in the cells of men without prostate cancer.

ConfirmMDx, which is a test that looks at certain genes in the cells from a prostate biopsy sample

These tests aren’t likely to replace the PSA test any time soon, but they might be helpful in certain situations. For example, some of these tests might be useful in men with a slightly elevated PSA, to help determine whether they should have a prostate biopsy. Some of these tests might be more helpful in determining if men who have already had a prostate biopsy that didn’t find cancer should have another biopsy. Doctors and researchers are trying to determine the best way to use each of these tests.

New research regarding prostate cancer prevention

Researchers continue to look for foods (or substances in them) that can help lower prostate cancer risk. Scientists have found some substances in tomatoes (lycopenes) and soybeans (isoflavones) that might help prevent prostate cancer. Studies are now looking at the possible effects of these compounds more closely.

Scientists are also trying to develop related compounds that are even more potent and might be used as dietary supplements. So far, most research suggests that a balanced diet including these foods as well as other fruits and vegetables is probably of greater benefit than taking these substances as dietary supplements.

One vitamin that may be important in prevention is vitamin D. Some studies have found that men with high levels of vitamin D seem to have a lower risk of developing the more lethal forms of prostate cancer. Overall though, studies have not found that vitamin D protects against prostate cancer.

Many people assume that vitamins and other natural substances are safe to take, but recent research has shown that high doses of some may be harmful, including those in supplements marketed specifically for prostate cancer. For example, one study found that men who take more than 7 multivitamin tablets per week may have an increased risk of developing advanced prostate cancer. Another study showed a higher risk of prostate cancer in men who had high blood levels of omega-3 fatty acids. Fish oil capsules, which some people take to help with their heart, contain large amounts of omega-3 fatty acids.

Some research has suggested that men who take a daily aspirin for a long time might have a lower risk of getting and dying from prostate cancer. Still, more research is needed to confirm this, and to confirm that any benefit outweighs potential risks, such as bleeding.

Scientists have also tested certain hormonal medicines called 5-alpha reductase inhibitors as a way of reducing prostate cancer risk

New research on gene changes for prostate cancer


New research on gene changes linked to prostate cancer is helping scientists better understand how prostate cancer develops. This could make it possible to design medicines to target those changes. Tests to find abnormal prostate cancer genes could also help identify men at high risk who might benefit from screening or from chemo-prevention trials, which use drugs to try to keep them from getting cancer.

Most of the gene mutations that have been studied as factors that might increase prostate cancer risk are from chromosomes that are inherited from both parents. Some research has found that a certain variant of mitochondrial DNA, which is inherited only from a person’s mother, might also raise a man’s risk of developing prostate cancer.

Prostate cancer detection from urine RNA steps closer

Testing for non-coding RNA molecules in urine may offer a way to detect prostate cancer that is more accurate and reliable than current methods using biomarkers such as PSA and PCA3.

The researchers believe using non-coding RNAs as biomarkers will lead to more reliable and accurate tests for prostate cancer than the current PSA test.

This was the conclusion of a German study presented at the European Association of Urology Congress (EAU16) in Munich, Germany, March 11-15, 2016.

Friedemann Horn, a professor in the University of Leipzig and the Fraunhofer Institute for Cell Therapy and Immunology IZI, and Manfred Wirth, a professor in the University of Dresden – both in Germany – led the work. Prof. Wirth says:”Our work on RNAs [ribonucleic acid] is allowing us to design a completely new kind of prostate cancer test.”

Current biomarker tests for prostate cancer measure levels of PSA (prostate-specific antigen) and PCA3 (prostate cancer gene 3), but they are not particularly accurate and can either miss many cancers or produce false positives.

The researchers behind the new study have identified a series of non-coding RNA molecules that could potentially be combined into a single urine test to detect prostate cancer.They say their test could offer greater sensitivity and specificity than the current biomarker tests and thus make population screening much more viable.

A test with high sensitivity is good at ruling out disease when the result is negative, and a test with high specificity is good at ruling in disease when the result is positive.Non-coding RNAs showed better specificity and sensitivity.

Progress in genomic science is revealing that genetic programming in human beings and other higher organisms is far more intricate and complicated than we thought. It appears our bodies express a huge repertoire of previously overlooked molecules that orchestrate a hidden layer of genetic signals involved in health and disease.

Fast facts about prostate cancer

• Other than skin cancer, prostate cancer is the most common cancer in American men
• About 1 man in 7 will be diagnosed with prostate cancer during his lifetime
• The average age at the time of diagnosis is about 66.

Learn more about prostate cancer

One group of these genetic molecules is non-coding RNA. RNAs are molecules that help to read and translate DNA (deoxyribonucleic acid) to make proteins – the workhorses of cells.Until recently, it was thought that many RNAs that do not help make proteins – called non-coding RNAs – were simply “junk” and had no particular function.

Now, greater understanding of non-coding RNAs reveals they help control many biological processes, including the development and progression of cancer, and measuring them could offer a way to detect disease.

For their study, the researchers took 64 prostate cancer tissue samples obtained from biopsies and read 200 million sequences in genetic molecules from each sample. They found over 2,000 sequences that were significantly different in tumor samples than in healthy controls.

Some of these sequences were for non-coding RNAs that showed better specificity and sensitivity than established prostate markers.The biomarkers were also found to be present in urine samples from cancer patients, and initial tests suggest they offer a precise way to detect the disease.

Combination of biomarkers will give better specificity

One of the non-coding RNAs – called tumor-associated proliferation-inducing RNA (TAPIR) – also showed significant promise in stopping cancer cell growth. However, the team says it is too soon to say whether this result will prove to be clinically useful.The team is now developing a highly specific and sensitive urine test for the early diagnosis of prostate cancer. The test will use a combination of biomarkers rather than just a single one.

Prof. Wirth says the work is still in the early stages, but results look promising. It offers a new approach to diagnosing prostate cancer and arises from applying basic science to a clinical problem. He concludes: “Given that our initial results show a high specificity for prostate cancer in urine tests, the prospects are good that we will be able to translate this into a better test for prostate cancer. We have several good candidate biomarkers, however we are aiming to design a test which utilizes a combination of biomarkers. This will give significantly better specificity than existing tests.”

The study is part of a project called RIBOLUTION (RIBOnucleic acid-based diagnostic soLUTIONs) – funded by the Fraunhofer Future Foundation – that aims to identify new RNA biomarkers and to develop novel diagnostic tests. The American Cancer Society estimate that in 2016, about 180,890 American men will be diagnosed with prostate cancer, and about 26,120 will die of the disease. Meanwhile, Medical News Today recently learned that the survival time for men with metastatic prostate cancer may depend on which part of the body the disease spreads to.

New connections revealed in regards to prostate cancer and DNA mutation

Specific mutations in the DNA of men with metastatic prostate cancer have been shown to play a larger role in the disease than previously thought. Researchers hope that this finding will help change standard therapy guidelines and open the door to drugs currently being used for other cancers.

Gene mutation research gives a new perspective on prostate cancer.

The new study, published in the New England Journal of Medicine, examined inherited mutations in DNA repair genes. These gene mutations were already known to occur more frequently in prostate cancer patients than the general population.

However, the present study demonstrated that mutations in DNA repair genes were even more prevalent in people with metastatic prostate cancer, specifically.

The research was headed up by Dr. Peter Nelson, a member of the Human Biology, Clinical Research, and Public Health Sciences divisions at Fred Hutchinson Cancer Research Center, WA. The team found that more than 10 percent of men with aggressive prostate cancer displayed inherited mutations in DNA repair genes.

These particular mutations occur in DNA repair genes such as BRCA1 and BRCA2, both of which produce tumor suppressor proteins. These DNA repair genes, as the name suggests, help maintain the integrity of the genetic code. If they are mutated, the DNA is less likely to be repaired correctly, increasing the risk of cancer.

BRCA1 and BRCA2 genes are already known to increase the risk of female breast and ovarian cancer. These two genes alone account for 20-25 percent of all hereditary breast cancers. So, although the role of these genes in cancer is known to be important, their influence in metastatic prostate cancer was not fully recognized.

DNA repair genes and metastatic prostate cancer

The researchers found that 11.8 percent of men with metastatic prostate cancer (regardless of age or family history) had mutations in one of the 20 DNA repair genes they screened for. That’s around four times the rate found in the general population and twice as much as the rate found in men with localized prostate cancer.

BRAC2 showed the clearest change in gene prevalence; men with advanced prostate cancer were 18 times more likely to have a mutation in their BRCA2 gene when compared with men without prostate cancer.

The researchers state their results are important for men who have been diagnosed, as well as for family members who might be at risk:”The result is surprising and important for men with prostate cancer as this information may prioritize certain therapies. It is also important for family members as they may have inherited a gene that predisposes them to developing one of several types of cancer, and heightened awareness could enhance early detection and treatment,” says Dr. Peter Nelson.

In total, the research team used data from 692 men with metastatic prostate cancer across a number of sites, including the Fred Hutchinson Cancer Research Center and the University of Washington. All of the institutions involved in the study carried out independent screening of 20 distinct DNA repair genes.

Importantly, the men used in the current study were not chosen because of family history or age, giving the results extra reliability. Additionally, the independent screening across multiple laboratories produced the same results across the board, adding further strength to the findings.

The future treatment of prostate cancer

This research project could open the door to other forms of treatment for metastatic prostate cancer. PARP inhibitors and platinum drugs are already used in some cancer cases, such as treating ovarian cancer in people with DNA repair gene mutations. PARP inhibitors – poly (ADP-ribose) polymerase – prevent PARP from repairing the damaged DNA of cancer cells, steadily killing them off. Platinum drugs, including cisplatin, carboplatin, and oxaliplatin, also inhibit DNA repair, slowly destroying cancer cells which are unable to fix their faulty genes. The results of this study could lead to the approval of PARP inhibitors and platinum drugs for metastatic prostate cancer, improving overall chances of survival.

Prostate cancer controversy continues as metastatic prostate cancer cases surge

A decade-long increase in the number of men who have incurable prostate cancer at their initial diagnosis has been documented by an new study; an ominous finding that prostate cancer-screening proponents have been predicting.

Both screening and diagnosis of early-stage prostate cancer have declined, coinciding with recommendations from an influential government advisory panel. In 2008, the U.S. Preventive Services Task Force said not to do routine PSA blood testing of men over age 74. And in 2012, it said to not screen any men – not even those at high risk – because the harms of unnecessary treatment outweigh the benefits of catching cancer early.

Despite less testing, death rates have been falling since 2007.

The new analysis, published in the journal Prostate Cancer and Prostatic Diseases, is the first to find an increase in metastatic cancers.

The Northwestern University analysis does not necessarily reflect a national trend. The study used a national cancer database from more than 1,000 hospitals rather than a representative sample of the population, so researchers could not calculate rates of disease.

Nevertheless, the statistics are stark: The annual number of metastatic prostate cancers at first diagnosis rose from 1,685 in 2004 to 2,890 in 2013 – a 72 percent increase the researchers call a “skyrocket” in a news release. The upturn was even greater among men 55 to 69, the age group believed to benefit most from early detection because of their risk level and life expectancy.

Over the same period, early-stage cancer diagnoses dropped from 25,708 to 16,223, or 37 percent.

Given that the surge in metastatic cases began before the U.S. Preventive Services Task Force’s recommendations against routine PSA testing, other factors must also be at work, the Northwestern researchers concluded. They speculated that some tumors are more aggressive, and that better imaging technology has improved detection of the spread to lymph nodes or beyond.

But the implications, they wrote, “highlight the need for nationwide refinements in prostate-cancer screening.”
“If you don’t screen, you don’t detect it early”, said senior author Edward M. Schaeffer, chair of urology at Northwestern’s Feinberg School of Medicine. “This is going to affect mortality rates. Metastatic disease is incurable. They will die.”

Eric Horwitz, a Fox Chase Cancer Center radiation oncologist, said the new study gives credence to anecdotal reports of spikes in metastatic cases – and to fears that the shift away from screening has gone too far.”We really do need to adjust the guidelines,” Horwitz said.

Thomas Jefferson University prostate cancer researcher Karen E. Knudsen said, “The challenge will be to refine guidelines so as to not miss men who would have benefited from earlier therapy, while at the same time not overtreating patients with a low likelihood of developing lethal prostate cancer.”

In its controversial 2012 disavowal of PSA screening, the advisory panel concluded that early detection saves few, if any, lives, while treatment leaves many men with sexual or urinary problems or both. The panel said “most” cancers found by screening are innocuous and would not cause harm if left undiagnosed.

The task force, which influences insurance coverage, relied heavily on two major clinical trials that compared screening to no screening. A European trial showed screening reduced deaths by 21 percent. A U.S. trial found no difference in death rates, but it has been widely dismissed as flawed because so many men in the no-screening group got PSA tests anyway.

Asked about the new study, panel chair Kirsten Bibbins-Domingo, an epidemiologist at the University of California, San Francisco, said in an email: “The Task Force welcomes new research. . . . As part of our normal process, we are currently reviewing the latest evidence to update our 2012 recommendation.”

She said that any man who is concerned about his risk of prostate cancer should talk to his doctor, “as this recommendation does not preclude a man choosing to be screened.”
Debate about the value of screening has raged for decades for both prostate and breast cancers.

Even Dartmouth Medical School researcher H. Gilbert Welch, an outspoken critic of overdiagnosis and overtreatment, believes the advent of routine PSA testing a quarter-century ago explains a “steep” decline in metastatic prostate disease.

Welch analyzed a federal cancer database and found the incidence of metastatic cases fell by half in the seven years after the start of widespread PSA use in 1990. “It’s hard to imagine another factor . . . exerting an effect so quickly,” Welch wrote last year in the New England Journal of Medicine.

The Northwestern study’s inability to calculate rates leaves unanswered questions. Perhaps the hospitals’ increase in advanced disease simply reflected a proportionate increase in the vulnerable age group – namely, older men.

“It is very possible” that less early detection will result in more advanced disease, said Otis Brawley, chief medical officer for the American Medical Association and a critic of overdiagnosis. “They simply did not prove it.”

Prostate cancer remains the second-leading cause of cancer death among men, behind lung cancer, so finding the right balance between early detection and overdiagnosis is essential. Schaeffer said his team plans to publish a profile of the metastatic patients in their study, analyzing their age, race, education, income, insurance coverage, and PSA level. The insights, he hopes, will help target screening to the men who need it most.

The task force four years ago “basically shot a volley across the bow, saying that screening the average person is not warranted,” he said. “If you can understand who is diagnosed with metastatic disease, that would be one way to be smarter about screening.”