Vigorous long term exercise may lower risk of advanced and fatal prostate cancers

Prostate cancer is one of the most common forms of cancer affecting men today. In 2018, more than 1.2 million new cases of prostate cancer will be diagnosed globally, according to the International Agency for Research on Cancer. While the burden of the disease is staggering, new research led by Harvard T.H. Chan School of Public Health suggests that a modifiable lifestyle factor may help reduce the risk: exercise.

Some researchers have long suspected that physical activity, and its influence on a wide range of biological processes including anti-inflammatory and insulin pathways, may be linked to a lower risk of prostate cancer. But findings from large epidemiologic studies so far have been mixed—some have shown an association, some haven’t.

In order to bring a fresh approach to the question, scientists from Harvard Chan School analyzed data from 49,160 men between the ages of 40 and 75 who enrolled in The Health Professionals Follow-up Study in 1986 and were followed to 2012. The men responded to biennial questionnaires that included questions about diet, health, and physical activity. Among the participants, 6,411 developed prostate cancer and 888 developed a lethal form of the disease.

This study, which was published in European Urology, showed that men who engaged most frequently in vigorous activity over the length of the study had a 30% lower risk of developing advanced prostate cancer and 25% lower risk of developing lethal prostate cancer when compared with men who exercised the least. On average, men in the highest category of vigorous activity engaged in an equivalent of 25 minutes of running daily. Vigorous activity for this study included activities such as bicycling, swimming, heavy outdoor work, and playing sports such as tennis or racquetball.

In addition to other well-known health benefits of a physically active lifestyle, this study emphasizes that prostate cancer prevention may be another important reason for men to move more and be active.

As well as being one of the largest of its kind, the study is unique in that the researchers were able to examine medical records, pathology reports, and disease-specific questionnaires, and to leverage molecular sub-typing data to better understand how prostate cancer develops.
In particular, the study homed in on a common molecular alteration in prostate tumors called TMPRSS2:ERG, a gene fusion that occurs in the tumors of about 50% of prostate cancer patients. The study showed for the first time that long-term vigorous physical activity was specifically associated with a lower risk of developing TMPRSS2:ERG-positive prostate cancers.

New approach against the most aggressive type of prostate cancer gets funding

The “Impact Award” has been granted by The U.S. Department of Defense to a multidisciplinary team of researchers made up of the Prostate Cancer Clinical Research Unit of the Spanish National Cancer Research Centre (CNIO), led by David Olmos, the Prostate Cancer Translational Research Group of the Vall d’Hebron Institute of Oncology (VHIO), led by Joaquín Mateo, and the Genetics and Solid Tumors Laboratory of the University of Washington, led by Colin Pritchard. This team will explore new therapeutic options against advanced prostate cancer—scientifically known as castration-resistant or hormone therapy resistant prostate cancer- They will receive a 2 million dollar grant for this 3-year project and will examine the identification of new markers as predictors of response to treatment, with the aim of identifying which patients will respond worse to therapy and thus offer them other therapeutic options.

Prostate cancer is one of the most common cancers in males in Spain and in the West and the second world-wide. It is the third most common cause of male death in Europe, even though over the last several years the survival rate is continually rising, most likely due to early detection. The most common treatment in the advanced stage is the hormone-blocking therapy, but some patients develop aggressive tumors that are resistant to this type of treatment: up to 90% of the patients that develop resistance also develop metastasis, most commonly in the bones and lymph nodes, but also occasionally in the liver and lungs. The average survival rate of the patients in the advanced stage is about 2 years after the diagnosis. Moreover, one in three patients respond worse to the approved therapies for prostate cancer, but until this day we do not have a better way of identifying and predicting their response to treatment.

This project will try to identify this group of patients through the development of new markers as predictors of response to treatment and will conduct a clinical trial to test if the therapy that works for other tumor types like breast and ovarian cancer could prove to be effective for the patients with advanced prostate cancer that show these markers.

Disruption of DNA repair mechanisms in tumors

The researchers will investigate the genetic and molecular changes associated with defects in the DNA repair mechanisms; that is, if the tumor cells repair the errors produced in their genetic material correctly or not. “Our line of work has always looked into those mechanisms” explains Elena Castro, from the CNIO Prostate Cancer Clinical Research Unit. “It is an approximation that has given very good results in prostate cancer research”. The researchers expect these tumors to respond to carboplatin therapy, a drug that is very effective in the tumor types that show these kinds of defects, such as breast and ovarian cancer. These therapies work by impeding that the cells repair their DNA defects. Due to the fact that cancer cells have far many more genetic defects than normal cells, these drugs are very effective in producing their breakdown and death.

In the first part of this project, the team will study the tumor samples that were collected from the patients participating in the PROREPAIR-B study; the first worldwide prospective study conducted, to date, in patients with advanced prostate cancer that carry heritable mutations. PROREPAIR-B is a study coordinated by CNIO that has monitored more than 400 patients since 2013, to analyze if their DNA damage repair genes have inherited genetic alterations and how these affect their response to treatment. Now these samples will be sequenced to check the behavior of the alterations in these genes that are not inherited and that only occur in the tumor.

After that, the VHIO team led by Joaquín Mateo will search for biomarkers for DNA repair defects in those patients, since these defects not always originate from an inherited genetic mutation. “Over the last few years we have shown that an important number of patients with advanced prostate cancer develop DNA repair defects in their tumors, even though there is no inherited mutation”, explains Joaquín Mateo, VHIO researcher and Vall d’Hebron University Hospital oncologist. “We also know that some of the tumors behave in a similar manner to the ones having these mutations, even if we don’t identify them. This is why we wish to study the biological patterns associated with the clinical patterns and to do that we will study these tumors using different tools in the laboratory”, adds Mateo. The goal is to find new signs of these errors (more than just genetic mutations) that would permit a faster decision-making on which treatments to choose.

Lastly, the CNIO team, with the help of VHIO and other Spanish centers, will conduct a clinical trial to confirm if the carboplatin therapy could be effective in advanced prostate cancer. “We know that carboplatin works really well in tumors with DNA repair defects from patients with breast and ovarian cancer, and we suppose that it will also work for patients with prostate cancer, but we are not certain at this stage”, says Olmos. “But instead of selecting patients based on them having genetic mutations that could provoke defects in DNA repair, as is commonly done, they will be selected using biomarkers that were previously detected, as we believe that it will be more reliable when determining the efficacy of the treatment. In other words, we will select patients based on whether the tumor repairs its DNA or not, independently of their genetic profile”.

Another advantage is that this therapy is affordable and easily accessible. A type of drugs that are known to be effective on tumors with DNA repair defects are the PARP inhibitors, but their price is high. “If carboplatin proves to be a good therapeutic option, the results of our trial will have a positive impact on the patients”, concludes Olmos. Mateo adds: “Since it is a drug that has already been approved and has been routinely used for other types of cancer, like breast and ovarian cancer, carboplatin’s way to the clinic to benefit patients with prostate cancer will be much shorter than usual. There is little experience with this drug for the treatment of the prostate cancer, but for now it looks promising. What we aim with this study is to be able to confirm it”.

Research shows 30% fewer prostate cancer deaths with PSA screening

PSA-screening cuts deaths from prostate cancer by 30%. This is based on research data from 20,000 men monitored for more than two decades. The PSA level initially measured in these men proved highly significant as a predictor of future cancer risk.

This research is important because it shows the long-term effects of an organized screening program.

The main purpose of this research was to enhance understanding of the implications of screening, and of the possible design of a future screening program for prostate cancer.

The study was unique in many ways, and to date, has the longest follow-up period of all screening studies on prostate cancer worldwide.

The Randomized Population-Based Prostate Cancer Screening Trial initially was comprised of a total of 20,000 men aged 50-64. 10,000 were randomly selected for a screening group and offered PSA testing (screening) every two years and cell sampling if elevated PSA levels were found. The remaining 10,000 were assigned to the control group and not offered PSA sampling in the study.

After 22 years of follow-up, approximately 300 men had died of prostate cancer. The risk was 30 percent lower for men who had undergone screening in the program. Men at the highest risk of dying from prostate cancer were those whose screening started after age 60; men who were diagnosed after leaving the study (aged about 70 and over); and those who were invited, but did not participate at all.

The study also included outcomes for men who participated in the screening program and left the trial without prostate cancer being detected. Among the men who were monitored for nine years after their screening ended, 200 cancer cases altogether were found. Of these men, 21 later died from the disease.

PSA levels on the first screening occasion proved to have a major bearing on future cancer outcomes. They may therefore be used for risk estimation. The results also showed that in men with voiding dysfunction — difficulty in emptying the bladder — the risk of prostate cancer was lower than in symptom-free men in the study.

Historic Funding for Prostate Cancer Research Maintained by Congress

The U.S. Senate and House recently released their conference report on the 2019 Defense Appropriations Bill, which once again allocates $100M to the Prostate Cancer Research Program (PCRP).

Approximately one year previous, Congress increased the PCRP at the Department of Defense (DoD) budget by $10M, returning the program to its 2001 funding level for the first time in 18 years.

The PCRP budget has been at $100M for the first time in back to back years. This increase could mean a brighter future for men fighting prostate cancer, and the funds could possibly lead to new groundbreaking treatments and diagnostic tools.

In February hundreds of passionate advocates spent countless hours meeting with their elected officials through ZERO’s Summit in Washington, D.C. Many then spent time on the telephone lines. They also pounded the pavement during a recess period by attending in-district meetings.

The move to increase research funds at the PCRP is at the top of ZERO’s Summit agenda. This program works with patients to identify gaps in research and care. It then awards talented scientists who are pursuing advancements to eliminate those identified areas of need.

The research funded by the PCRP is more critical than ever as Surveillance, Epidemiology, and End Results (SEER) data from the National Cancer Institute predicted deaths to jump by 3,000 in 2018 alone.

More than 164,000 men will be diagnosed with prostate cancer this year and nearly ten percent of those diagnoses will occur among our nation’s veteran population.

Researchers determine that aggressive prostate and lung cancers are driven by common mechanisms

A common process in the development of late-stage, small cell cancers of the prostate and lung has recently been discovered. The discovery of these shared molecular mechanisms could lead to the development of drugs to treat prostate and lung cancers, but other small cell cancers of almost any organ as well.

The key finding of the research is as follows: Although prostate and lung cells have very different patterns of gene expression when they’re healthy, they have almost identical patterns when they transform into small cell cancers. This new research suggests that different types of small cell tumors evolve similarly, even when they come from different organs.

Cancers that become resistant to treatment often develop into small cell cancers which generally have extremely poor prognoses. They are also known as small cell neuroendocrine carcinomas, or SCNCs. Certain cancers can evade treatment; they do this in part by changing cell types such as changing from aggressive adenocarcinoma to small cell carcinoma.

Previously some research had hinted that small cell cancers from different organs may be driven by common mechanisms, but this recent study is the first to clearly describe the steps in the evolution.

The study’s authors and collaborators explored the potential parallels between cancer types by transplanting human prostate cells with five genes, known collectively as PARCB, into mice. When the transplanted cells grew within the mice, the cells displayed unique features of human small cell neuroendocrine carcinomas.

As part of the study the team also identified that for small cell neuroendocrine carcinomas to develop in the prostate, two tumor suppressor genes, TP53 and RB1, had to be simultaneously inactivated when PARCB was introduced. TP53 and RB1 are known for protecting normal cells from transforming into cancer cells.

Additional tests confirmed striking similarities between the PARCB-SCNC cells and small cell prostate cancer cells from humans. In particular, RNA expression and the turning on and off of certain genes were nearly identical. The team found that the similarities between the PARCB-SCNC cancers and human small cell prostate cancers were extraordinary.

Large databases of gene expression were looked at in order to compare the patterns of gene expression in their PARCB-SCNC cells to cancers of other organs. The team found that the pattern of gene expression in PARCB-SCNC cells was extremely similar to those of both prostate and lung small cell cancers.
They then tested whether PARCB genes could alter healthy cells from human lungs into small cell lung cancers. The scientists determined that this was possible.

The team is also working on mapping which genes control the entire cascade of events that underlies the transition to small cell cancer. Studying the network of the master gene regulators may lead to a new way of combating deadly cancers.

When baseline PSA levels are measured in black men at midlife, the test can predict the risk of aggressive prostate cancer

Even though black men are more likely to be diagnosed with, and to die from, prostate cancer, recommendations about prostate cancer screening are primarily based on studies of white men. A recent study led by investigators at Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health focused exclusively at results among black men. The study addressed whether an optimized screening strategy with baseline prostate specific antigen (PSA) levels predict prostate cancer in this population. The study findings found that baseline PSA levels in black men measured at midlife strongly predicted the risk of total and aggressive prostate cancer in the future.

The researchers found that a single, baseline PSA level measured during midlife strongly predicted subsequent diagnosis of total and aggressive prostate cancer up to 12 years after a blood draw. These findings suggest that targeted screening based on a midlife PSA for black men might identify those at high risk of aggressive prostate cancer. The screenings could also minimize future screenings for those at low risk.

Compared to white men, black men in the U.S. are 2.5 times more likely to die of prostate cancer. However, screening studies to date have largely been focused solely on white men. Therefore the data from this study addresses a critical gap in understanding the substantial racial disparities. It also suggests a potential strategy to reduce prostate cancer death in black men.

The research team involved took a targeted, risk-stratified approach, leveraging data on men enrolled in the federally funded Southern Community Cohort Study, a collection of 86,000 men and women from the Southeastern U.S., that included more than 22,000 black men.

The data showed that 95 percent of total and 97 percent of aggressive prostate cancer cases had baseline PSA above the average for their age group. Compared to men with PSA at or below the age-specific median, men with levels above the median had significantly increased risk of aggressive prostate cancer across age groups. Men with PSA levels above the 90th percentile had the greatest risk.

The research showed that increased risk was seen with PSA levels that were higher than the average but still well within the “normal” range – and low enough not to trigger follow-up in usual clinical practice.

The findings do not necessarily imply that prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline. This conclusion could lead to over-diagnosis. However, the researchers determined that these men should undergo more intensive PSA screening to enable earlier identification of cancer and potential cure while still possible.

Consumer test for certain BRCA mutations get FDA approval

The FDA (US Food and Drug Administration) has approved the first direct-to-consumer tests for certain BRCA1 and BRCA2 gene mutations. Those people who have inherited these gene mutations have a higher than average risk of developing certain cancers. These gene mutations can also be passed down to their children. In the US, BRCA mutations are more common in Ashkenazi Jews, but it has been shown that people of other racial and ethnic groups can also have them.

These newly-approved tests are for 3 specific BRCA gene mutations. For women who test positive for one of the mutations, risk of developing breast and ovarian cancers is increased. For men who test positive for one of the mutations, their risk of developing breast and prostate cancer is increased. There are more than 1,000 known BRCA mutations, however, and the three included in the newly-approved test are not the most common ones. So in essence, this means there are many BRCA mutations that would not be detected by this test.

According to the FDA, problems can result if the test results are used without consulting a medical professional. This test should not be used as a substitute for cancer screening or genetic counseling that may be recommended by a medical professional based on the risk for cancer. The FDA also says that this new test does not provide information on a person’s overall risk of developing any type of cancer.

Taking the test

The FDA granted authorization for marketing the test to 23andMe. The test is very simple to take; people who order the test kit collect a small amount of saliva in a container and mail it to a laboratory for analysis. Then a report with the results is mailed back to the consumer.

According to the FDA, BRCA gene mutations detected by the test are present in only about 2% of Ashkenazi Jewish women, and in less than 0.1% of the US population overall.

Most cases of cancer are not caused by hereditary gene mutations. They are thought to be caused by a wide variety of factors, including smoking, obesity, hormone use and other lifestyle issues. Advice from a health care professional can help people understand how these factors impact their individual cancer risk.

And while it is understandable that people with a family history of cancer may want to learn their genetic makeup, genetic testing is not helpful for everyone. If you believe that cancer runs in your family, and you have a reason to think you might benefit from genetic testing, it’s best to talk with your health care provider and plan to meet with a genetic counselor before taking any genetic test. This helps people know what to expect. The genetic counselor can tell you about the pros and cons of the test, what the results might mean, and what your testing options are.

Adult obesity rates in the U.S. continue to climb

Over the past decade the rates of American adults with obesity have continued to increase according to researchers from the Centers for Disease Control and Prevention (CDC). In the years between 2007-2008 and 2015-2016, the report says the rates of obesity in adults in the U.S. rose significantly, from 33.7% to 39.6%. Moreover, the rates of severe obesity increased during this time from 5.7% to 7.7%. The CDC report was published online March 23, 2018 as a research letter in the Journal of the American Medical Association.

The CDC’s report defines obesity as having a body mass index (BMI) of 30 or greater and defines severe obesity as having a BMI of 40 or greater. As an example, an adult who is 5’ 9” tall and weighs 203 pounds has a BMI of 30. An adult who is 5’ 9” tall and weighs 271 pounds has a BMI of 40. According to the CDC, a healthy weight for an adult this height is between 125 and 168 pounds.

This new report also shows an overall trend toward a slight increase in obesity rates among youth ages 2 to 19, but this increase is not steep enough to be statistically significant.

The researchers made these study calculations using data from 27,449 adults and 16,875 youth enrolled in the National Health and Nutrition Examination Survey.

Cancer and obesity

People with obesity have a significantly higher risk than people of healthy weight to develop many serious diseases and health conditions, including heart disease, stroke, type 2 diabetes, and certain cancers.

The factor of being overweight is clearly linked with cancers of the breast (in women past menopause), colon and rectum, endometrium, esophagus, kidney, and pancreas. Beyond that there is also evidence that excess weight may contribute to cancers of the gallbladder, liver, cervix, and ovary, as well as non-Hodgkin lymphoma, multiple myeloma, and aggressive forms of prostate cancer. Studies have shown that excess body weight is thought to be responsible for about 8% of all cancers in the United States, as well as about 7% of all cancer deaths.

But people need not despair. Even a small weight loss – for instance, 10% of your current weight – lowers the risk of several diseases.

The American Cancer Society recommends that people try to get to and stay at a healthy weight throughout life by eating a healthy diet and by getting plenty of physical activity. A healthy diet can include vegetables and fruits, whole grains, beans, and lower calorie beverages. It is recommended that people limit high-calorie foods, between-meal snacks, and added sugars.

It is also recommended that adults get at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity activity each week (or a combination of these), preferably spread throughout the week. All children and teens should get at least 1 hour of moderate or vigorous intensity activity each day, with vigorous activity on at least 3 days each week. Moderate activity is about the level of a brisk walk, while vigorous activity is defined by exercise that increases your breathing and heart rate, and makes you sweat.

Why do doctors screen for some cancers and not others?

The definition of screening means having a test that looks for cancer or another disease in people who don’t have any symptoms. In some instances, screening tests can find growths and remove them before they have a chance to turn into cancer. There are other screening tests that can find cancer early when it’s easier to treat.

We must weigh the benefits of screening tests against the risks of the tests themselves. There are risks that may include anxiety, pain, bleeding, or other side effects. Also we need to consider that screening isn’t perfect. It sometimes screening misses cancer, and conversely it can find something suspicious that turns out to be harmless (which is called a false-positive). Then that finding needs to be checked out through additional tests that also carry risks and cause more stress.

The American Cancer Society uses a formal process to review scientific evidence to create guidelines for cancer screening for all these reasons. The guidelines simply advise people about what screening tests they should get, when they should get them, and how frequently the tests should be done. The higher a person’s risk for cancer – due to risk factors such as age, family history, or other factors – the more likely the benefits of screening will outweigh the risks.

American Cancer Society Screening Guidelines

These guidelines for average-risk adults recommend regular screening for breast cancer, cervical cancer, and colorectal cancer, based on scientific evidence that shows those screenings save lives.

When the benefits and risks of screening for prostate cancer and lung cancer are weighed, the issue becomes more complicated because other individual factors are involved. Therefore, the American Cancer Society recommends that people become informed and talk with their doctor regularly to make the screening decisions that are best for them.

When it comes to many other cancer types, researchers continue to conduct studies to learn the best ways to find cancer before symptoms appear.

Prostate Cancer: Men should discuss the possible risks and benefits of prostate cancer screening with their doctor before deciding whether to be screened. The discussion should take place starting at age 50 for men who are at average risk of prostate cancer and expect to live at least 10 more years. It should take place at age 45 for men who are at higher risk, including African American men and men who have a father or brother diagnosed with prostate cancer, and at age 40 for men at even higher risk. Talk to your doctor about your history, and what screening schedule is best for you.

Breast Cancer: Women should be able to start screening at age 40 if they want to. All women at average risk of breast cancer should begin yearly screening by age 45. At age 55, women can choose to continue with yearly mammograms, or choose to have them every other year. Women should talk to their doctor about their own personal risk for breast cancer and about any breast changes they notice. Regular mammograms should continue for as long as a woman is in good health.

Cervical Cancer: Women between the ages of 21 and 29 should have a Pap test every 3 years. Women between the ages of 30 and 65 should have both a Pap test and an HPV test every 5 years, or a Pap test alone every 3 years. Women over age 65 who have had regular screening tests with normal results should no longer be screened for cervical cancer. Women who are at high risk for cervical cancer may need to be screened more often. Talk to your doctor about the screening schedule that is best for you.

Colorectal Cancer: Adults at average risk should begin regular colorectal screening at age 45, but those with a family history or other risk factors should talk with their doctor about beginning earlier. Several different tests can be used to screen for colorectal cancer, including colonoscopy, flexible sigmoidoscopy, guaiac-based fecal occult blood test, and more. Discuss which test is right for you with your doctor, and talk to your insurer about coverage. All abnormal results on non-colonoscopy screening tests should be followed up with a colonoscopy.

Lung Cancer: People at high risk for lung cancer may benefit from low-dose CT scan (LDCT). “High risk” refers to current smokers (or those who have quit within the past 15 years) 55 to 74 years old who have a smoking history of 30 pack-years or greater. This means smoking an average of 1 pack a day for 30 years, 2 packs a day for 15 years, or the equivalent. Talk to your doctor about your risk, and the benefits, limits and harms of screening with LDCT.

Hot dogs, hamburgers and bacon; what’s the harm?

The cancer arm of the World Health Organization has come forward with some serious concerns about some of Americans’ favorite foods.

According to the International Agency for Research on Cancer, processed meat has been classified as a carcinogen, or in other words, something that causes cancer. It has also classified red meat (unprocessed) as a probable carcinogen, which is something they believe could probably causes cancer.

What is included in the term processed meat? It includes hot dogs, ham, bacon, sausage, and some types of deli meats. Processed meat meat that has been treated in some way to preserve or flavor it. The processes involved may include salting, curing, fermenting, and smoking. The different types of red meat include beef, pork, lamb, and goat.

A team of 22 experts from 10 different countries reviewed more than 800 studies to reach these conclusions. The findings that eating 50 grams of processed meat every day increased the risk of colorectal cancer by 18%. 50 grams is not a great deal of food; it is the equivalent of only about four strips of bacon or just one single hot dog. When it came to unprocessed red meat, they also found evidence of increased risk of colorectal, pancreatic, and prostate cancer.

The overall lifetime risk of someone developing colon cancer is 5%. To put the numbers into perspective, the increased risk from eating the amount of processed meat in the study would raise average lifetime risk from 5% to almost 6%.

The American Cancer Society and many other organizations have long recommended a diet that limits processed meat and red meat. They also encourage a diet that is high in vegetables, fruits, and whole grains. Their Guidelines on Nutrition and Physical Activity for Cancer Prevention recommend that people choose fish, poultry, or beans instead of red meat and processed meat.