The Pendulum Swings (Back) on Prostate Cancer Screening

The U.S. Preventive Services Task Force (USPSTF) has updated its guideline for prostate cancer screening. The group now recommends that men ages 55 to 69 who are interested in screening talk to their doctors about potential benefits and harms of screening for prostate cancer before deciding whether to be screened using the prostate-specific antigen (PSA) test. Previously, the USPSTF recommended against screening with PSA. Otis Brawley, M.D., MACP, American Cancer Society chief medical officer, weighs in below.

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Otis W. Brawley, M.D.

“These revised recommendations from the US Preventive Services Task Force essentially bring all experts groups, including the American Cancer Society into alignment on prostate cancer screening using PSA.  For some years, the ACS has called for shared decision making that incorporates individualized risks and concerns. Every man who accepts screening still should realize that there is a chance of benefit and a chance of harm. While the ACS says men at average risk start having this discussion at age 50, the USPSTF says it should happen at 55.

“Many wonder why the pendulum is swinging back towards screening, considering USPSTF’s previous guideline said there was inadequate evidence to support prostate cancer screening. The fact is, over the past few years, the benefit-to-harm ratio of PSA screening has improved as men diagnosed with prostate cancer have accepted the notion that their cancer can be watched, and if there are signs of trouble, treated. This approach, called “active surveillance,” reduces the harms of unnecessary treatment, tipping the balance towards informed decision-making.

“The USPSTF recommendation takes into account the most recent randomized trial of prostate cancer treatment and the recent treatment recommendations of a number of professional organizations.  The British study, known as ProtecT, showed that a large proportion of men with screen-detected early stage prostate cancer can be safely observed and will never need treatment. Recommendations of the American Urological Association, the American Society of Therapeutic Radiation Oncology, the Society of Urologic Oncology, and the American Society of Clinical Oncology now clearly state that active surveillance is the preferred management strategy for most men with low-risk disease. Today, about half of men with newly diagnosed localized disease enter active surveillance protocols. Most will never need aggressive therapy.

“Our ability to identify life threatening disease has improved dramatically, making observation an acceptable alternative to immediate treatment for many men. In addition, our understanding of prostate cancer biology and screening will make it easier for the average man to consent to screening. Still, every man accepting screening should realize that along with a chance of benefit, there is a chance of harm; a high rate of false positives, a high chance of having a prostate biopsy, and the inconveniences and side effects associated with those are essentially exchanged for a relatively small chance of one’s life being saved.

“It’s important for those considering screening to review the estimates of benefit and harm published by the Task Force, based on the large European trial. They say among 1,000 men are invited to screening over a 13 year period, there will be 240 false positives, leading to 220 transrectal biopsies; two men will be hospitalized for complications due to biopsy.  About 100 men will be diagnosed with prostate cancer, of whom about 50 will experience sexual dysfunction due to treatment; fifteen will experience significant urinary dysfunction. Screening would prevent three cancers from metastasizing, and one prostate cancer death (5 versus 6 without screening). These are sobering numbers about the true limits of screening.”

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Highly Processed Foods & Cancer Risk

Unhealthy Male Man Eating Indoors Fast Food BoothA study out Wednesday suggests eating a lot of highly processed foods might be associated with higher rates of cancer. The study appears in BMJ, and the authors admit more study is needed, but warn that the rapid adoption of what they call “ultra-processed foods” may increase the cancer burden in the coming decades.

We asked Marji McCullough, SCD, RD, strategic director of nutritional epidemiology for her thoughts on the study.

“This was a well-conducted study but we should be cautious about interpreting what exactly is responsible for the higher cancer risk.  For example, people eating more highly processed foods are eating fewer healthy foods that may reduce the risk of cancer.

“Highly processed foods are frequently packed with sugar, salt, fat and calories. The authors did try to control for these factors, but it’s difficult to totally control for these and other dietary components.

“Of note, a large proportion of the highly processed foods in this study were sugary products and beverages, which contribute to weight gain and add little nutritional value to the diet.

“In addition, people who eat more highly processed foods tend to have other unhealthy dietary and lifestyle behaviors which might not have been fully accounted for in this study.

“We know people who eat more processed and red meat, potatoes, refined grains, and sugar sweetened beverages and foods are at a higher risk of developing certain cancers. It’s still unclear what role processing has in this relationship; more research on this will be done to more carefully tease out this risk.

“In the meantime, this is one more piece of evidence that a diet rich in whole grains, whole fruits and vegetables, as recommended in the American Cancer Society guidelines, is beneficial for lowering cancer risk.”

Marji also had an important tip for shoppers: “Focus your shopping on the perimeter of the grocery store,” she says. “That’s usually where the whole foods tend to be; vegetables, fruit, whole grains, etc.”

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Rodents and Radiation: What to Take Away from New Study Findings

Preliminary data was released today from two rodent studies by the National Toxicology Program (NTP), to explore potential links between cell phones and cancer. The studies have found high exposure to radiofrequency radiation (RFR) resulted in tumors in tissues surrounding nerves in the hearts of male rats, but found no link in female rats nor in any mice. As is commonly done in these types of studies, researchers used exposure levels that were higher, and often far higher, than the amounts typically emitted by cell phones.

The authors say the new data does not go much further than what they reported in 2016.

Below are comments from Otis W. Brawley, M.D., in response to the new data.

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Otis W. Brawley, M.D.

“These draft reports are bound to create a lot of concern, but in fact they won’t change what I tell people: the evidence for an association between cell phones and cancer is weak, and so far, we have not seen a higher cancer risk in people. But if you’re concerned about this animal data, wear an earpiece.

“Perhaps the most important thing to take away from today’s news may be this line from the press release:

“The levels and duration of exposure to RFR were much greater than what people experience with even the highest level of cell phone use, and exposed the rodent’s whole bodies. So, these findings should not be directly extrapolated to human cell phone usage,” said John Bucher, Ph.D., NTP senior scientist.

“The animals in this study were exposed at high levels for 9 hours per day. So while the link to some rare cancers are important, there is no reason to think this study reflects real life exposures.

“Dr. Bucher confirmed this in a press conference with reporters, and when asked whether the new data has changed how he uses cell phones, he replied that it has not, nor has he told his family to change what they do.

“Some additional cautions: as one of the reporters on the press conference pointed out, while some radiated animals did indeed have more tumors, in fact they lived longer.  Also, it’s far from a slam dunk to apply findings in one species to another. Also, these studies were negative for common tumors, which is somewhat comforting. It suggests if anything, cell phone radiation may (and only “may”) be linked to some very rare tumors. And newer, lower energy cell phones, and more cell towers are likely to make exposures even lower.

“A final point to remember is that we should not base our decisions or our point of view on a single study. When deciding where the truth lies, you really need to take all the available evidence into account. And in fact, most studies looking into cell phones and cancer are negative.”

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Detecting cancer with a blood test: New study shows promise, but questions remain

A study published this week in Science reports promising results of a blood test designed to detect eight common cancer types by measuring circulating proteins and mutations in cell-free DNA. The study comes from the Johns Hopkins Kimmel Cancer Center at Johns Hopkins and has created a lot of buzz. We asked J. Leonard Lichtenfeld, M.D., MACP, deputy chief medical officer to share his thoughts about the study.

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Len Lichtenfeld, M.D.

“The study reported this week on the potential of cell free DNA providing another option for the early detection of cancer represents elegant science. It is one more step down what we expect to be a long path of discovery to determine if this approach is not only effective at early detection but, far more important, also improves outcomes for those diagnosed with cancer.

“The test is one of several approaches with a similar focus on the early detection of cancer. Which tests will achieve this goal is not certain at this time.

“It is important to remember that it is one thing to advance the science and the technology; however it is something entirely different to demonstrate that the test will actually make a difference in saving lives. Notwithstanding the results of this study in patients who have already been diagnosed with cancer, it is possible that we may find that the test will find cancers early and we won’t be able to accurately determine where the cancer came from. Or we may learn that simply find these cancers early may not make treatment more effective or impact lives to the degree we had hoped for. These are answers we need.

“In simpler terms:  we have a long way to go to demonstrate the utility and value of this test. We cannot make assumptions regarding the ability of this test to detect cancer early based on this study. We need additional research (which is being undertaken) to prove that it is possible to find cancer signals in the blood of patients before it is otherwise known they have cancers. Those studies are moving forward at this time.

“We have made assumptions in the past about the ability of blood tests to diagnose cancer early with—for example–tests for prostate and colon cancers. The prostate cancer experience should teach us that we need to prove value and utility before we again subject potentially millions of people to possibly unnecessary medical procedures and treatment which ultimately have not necessarily improved the length or the quality of their years.”

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Study links inflammation-causing foods to higher risk of colorectal cancer

A study in today’s JAMA Oncology links diets that include foods that can cause inflammation to an increased risk of colorectal cancer.  Those foods include meats, refined grains, and high-calorie beverages. We asked Marji McCullough, SCD, RD, strategic director of nutritional epidemiology at the ACS.

JAMA Onc“There has been a lot of interest in the role of diet in inflammation, and in fact several anti-inflammatory diets have begun to be promoted. This is an observational study, not interventional, so it has some limitations, but it does shed some light on the issue.

“There are several ways diet may influence colorectal cancer risk, including inhibiting or promoting inflammation, which is the focus of this paper. Chronic inflammation can cause DNA damage and lead to unregulated cell growth. Other ways diet could influence colorectal cancer risk is through antioxidant effects (protecting against DNA damage), influencing the cell cycle, and direct consumption of carcinogens.

“While it’s tempting to focus on specific foods, how overall diet contributes to this inflammatory effect is likely more important than individual foods because foods may act together in influencing disease risk.

“It’s possible the impact of diet is even greater than that measured in the current study, which captured only some of the foods that are likely to influence inflammation. For example, certain spices and food preparation methods that were not included may have strong effects on inflammation.

“It’s interesting to consider that what you eat may be just as important as what you don’t. In other words, many foods and beverages are substitutions for each other. One strength of this paper is that it takes the total diet into account.

“Another important aspect of this study is that it focused on foods, not supplements. It underscores how food can have significant roles in influencing disease risk.

“As far as what people should know about colorectal cancer and diet: The International Agency for Research on Cancer (IARC) determined that processed meat is a carcinogen, and red meat is a probable carcinogen, so lower intakes of both would reduce colorectal cancer risk. Whole grains and (low fat) dairy foods are associated with lower risk of colorectal cancer. Whole grains add bulk to the diet and may dilute carcinogens. Whole grains and other plant foods also contribute to beneficial microbiome diversity. Dairy foods contain calcium and vitamin D, which have beneficial effects on cell proliferation and differentiation.

“The bottom line: It’s important to consider the total diet, as a combination of lots of healthy foods and lower amounts of unhealthy foods are likely to have additive and synergistic effects on lowering cancer risk.”

 

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Behind the numbers: cancers associated with obesity

A report out today had a lot of us scratching our heads, when it said that about 630,000 people in the U.S. were diagnosed with a cancer associated with overweight and obesity in 2014.

That sounds awfully high, we thought.

It went on to say more than half, 55 percent of all cancers diagnosed in women and about one in four, 24 percent of those diagnosed in men are associated with overweight and obesity.

Now you got our attention.

We asked Farhad Islami, MD PhD, strategic director of cancer surveillance research to have a look. And it turns out there was a simple, and important explanation.

“It’s important to note that only a fraction of the cancers included in the calculation in this report are actually caused by excess body weight. For this study, the authors totaled all of the cancers diagnosed in 2014 for 13 types that have been linked to some extent with excess body weight. In other words, the reported number, 631,000 cancer cases representing 40% of all cancers diagnosed, represents all cases among those 13 types, even though not all of those cancers are caused by excess body weight. Many are attributable to other known risk factors, like smoking, while for many others, the cause is unknown. Obesity is more strongly associated with some cancers than others.

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Farhad Islami, M.D., Ph.D.

“As far as the actual estimate of the percentage of all cancers associated with obesity: The World Cancer Research Fund estimates that 20% of all cancers in the United States are caused by a combination of excess body weight, physical inactivity, excess alcohol, and poor nutrition. The American Cancer Society is currently doing its own extensive calculation of the numbers and proportions of cancer cases attributable to excess body weight, the results of which will be published soon.”

Update: Two days later, several headlines confirm this effort to highlight a real problem led to widespread misreporting obesity headlines

 

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New Analysis Confirms Suspected Bias of Large U.S. Prostate Screening Study

A new paper appearing in Annals of Internal Medicine used simulation modeling to try to correct for a known bias in a notable U.S. trial of prostate cancer screening, called PLCO. That study along with a large European one played an important role in the creation of screening guidelines from the American Cancer Society and others.

While the major European trial, called ERSPC, suggested routine PSA screening reduced the risk of prostate cancer death by about 30 percent in men who were very compliant with screening and treatment, the U.S. study failed to show a benefit. The U.S. trial is widely-believed to have been contaminated; many men in the control arm, who were assumed to be unscreened, were in fact screened thanks to the wide availability of PSA testing at the time, diminishing the differences between the studies two arms.

We asked Chief Medical Officer Otis W. Brawley, M.D. if the new data changes the current understanding of PSA screening.

“This new analysis supports the widespread understanding that PSA screening under optimal conditions has larger mortality benefits than were shown by a large U.S. trial. It also supports a move towards watchful waiting that all experts hope will make screening as useful as possible.

“The new analysis uses a measure known as ‘mean lead time’ to try to account for suspected biases in the U.S.-based PLCO trial. Some consider this modeling controversial and unproven. Nonetheless, it may be useful in this situation.

“The findings from the new analysis are consistent with the assessments of most experts, who generally agree that prostate cancer screening is associated with a reduction in prostate cancer deaths, and that the U.S. trial undercounted this benefit.

“Screening recommendations from the American Cancer Society and others have acknowledged the limitation of the U.S. trial, so this new analysis does not significantly change the body of evidence on which our recommendations are based.

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Otis W. Brawley, M.D., MACP

“A reduction in the risk of death is only half the equation when weighing whether to recommend screening. Guidelines from the ACS and others must weigh those benefits against some fairly serious side effects associated with screening and its subsequent treatment. The question is whether the benefit of widespread routine screening outweighs the risks of harm.

“The ACS was one of the first of many organizations that now recommend informed or shared decision making regarding prostate cancer screening, based on the fact that the potential benefits of screening can be offset by harms associated with the large number men who would be treated.

“Most organizations including the ACS now agree men in their 50s should be informed by their clinician regarding the potential benefits and risks of screening. This analysis will not change that recommendation. 

“Prostate cancer screening has been an area in need of clarity. This study validates the findings from the two major studies that prostate cancer screening does save lives.

“Those two studies also showed that many men diagnosed with prostate cancer through screening are candidates for observation rather than immediate, aggressive therapy.

“This approach, called watchful waiting, has lessened the harms associated with detecting prostate cancer through screening and has begun to change the risk benefit ratio.

“It is hoped that continuing the trend toward carefully selecting which men get screened for prostate cancer, developing better methods for distinguishing low and high risk prostate cancers, and carefully monitoring those who are found to have low risk cancer has the potential to optimize PSA screening to leverage its lifesaving potential while reducing harms of unnecessary treatment.”

For more information, see Can Prostate Cancer Be Found Early? on cancer.org.

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