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.


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

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Don’t Fry Day: Getting Sunscreen Right

Despite increased awareness about the dangers of ultraviolet (UV) radiation, melanoma rates continue to rise in the United States. For “Don’t Fry Day” on May 26, the American Cancer Society is cautioning that many people may be using sunscreen improperly, not only limiting its effectiveness but potentially increasing their risk of skin cancer.

melanomaData from the CDC’s Surveillance, Epidemiology, and End Results (SEER) program show rates of new melanoma cases have been rising for three decades, and on average 1.4% each year over the last 10 years. The rise comes despite heightened awareness about the dangers of UV radiation as well as widespread promotion of the use of sunscreen.

“Our fear is people are not using sunscreen correctly, and even when they do, many are using it inappropriately,” said Richard C. Wender, M.D., chief cancer control officer of the American Cancer Society. “People may be using sunscreen to go out in the sun in the middle of the day, when the risk is highest, and to stay out longer. Adding to the problem is the fact that many people do not use enough sunscreen and do not re-apply frequently enough.”

Rich Wender_5x7 Portrait

Richard C. Wender, M.D.

“People primarily worry about sunburn, which is understandable. Severe sunburns are an important risk factor for melanoma. But sunburn only tells you how much UVB radiation exposure you’ve had; it tells you very little about how much exposure you’ve had to UVA radiation,” said Dr. Wender.

While UVB is the chief culprit behind sunburn, UVA rays penetrate the skin more deeply, are associated with wrinkling, leathering, sagging, and other light-induced effects of aging. UVA rays also exacerbate the carcinogenic effects of UVB rays, and increasingly are being seen as a cause of skin cancer on their own.

Sunscreens vary in their ability to protect against UVA and UVB. Sun Protection Factor or SPF measures how effectively the sunscreen formula limits skin exposure to UVB rays that burn the skin. SPF does not measure UVA. Only “broad spectrum” sunscreens protect against both UVA and UVB.

“Sunscreens are important, no doubt,” says Dr. Wender. “But they should not be a first line of defense against the sun. The first line should be avoiding midday sun.”

The American Cancer Society recommends:

  • Seek shade Avoid being outdoors in direct sunlight too long between the hours of 10 am and 4 pm, when UV light is strongest.
  • Protect your skin with clothing: When you are out in the sun, wear clothing to cover your skin. Long-sleeved shirts, long pants, or long skirts cover the most skin and are the most protective. A tightly woven fabric protects better than loosely woven clothing. If you can see light through a fabric, UV rays can get through, too.
  • Wear a hat: A hat with at least a 2- to 3-inch brim all around is ideal because it protects areas that are often exposed to intense sun, such as the ears, eyes, forehead, nose, and scalp.
  • Wear sunglasses that block UV rays
  • Use sunscreen: Use an SPF 30 or higher broad spectrum sunscreen. Ideally, about 1 ounce, about a shot glass or palmful, should be used to cover the arms, legs, neck, and face of the average adult. Sunscreen needs to be reapplied at least every 2 hours to maintain protection.

While sunscreens with SPF above 50 are available, Dr. Wender says they offer little additional protection, and could backfire if people overestimate the additional protection they provide.

“SPF 30 sunscreens filter out about 97% of the sun’s UVB rays. SPF 50 brings that to about 98%, and SPF 100 to about 99%. So the higher you go, the smaller the difference becomes. And that number says nothing about UVA rays,” said Dr. Wender. “People may see the higher number, overestimate its ability to block additional rays, and increase their exposure and their risk. That’s why your first line of defense must be avoiding the bright sun in the middle of the day.”

The National Council on Skin Cancer Prevention (NCSCP designated the Friday before Memorial Day as “Don’t Fry Day,” a public awareness campaign that promotes sun safety and encourages people to protect their skin while enjoying the outdoors. Core members of NCSCP include the American Cancer Society, the American Academy of Dermatology, the Melanoma Research Foundation, and the Skin Cancer Foundation.

For more information, see: Skin Cancer Prevention and Early Detection on

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Ventilated Filters: Changing the Face of Lung Cancer in the U.S.

LungCawithPICCAn analysis appearing in the Journal of the National Cancer Institute finds strong evidence that adding ventilation holes to cigarette filters has contributed to a rise in a type of lung cancer called adenocarcinoma among smokers. The authors say the FDA should consider regulating the use of filter ventilation, up to and including a ban.

Eric Jacobs, Ph.D., strategic director of pharmacoepidemiology says the new analysis is a welcome addition to existing information about the dangers of ventilated cigarette filters and should lead to further research to find out whether regulation is warranted.

“Rates of lung cancer in cigarette smokers were already high in the 1950s and 1960s, but have increased over time, driven by increases in adenocarcinoma, now the most common type of lung cancer. The new review in the Journal of the National Cancer Institute is therefore important because it systematically lays out and evaluates the scientific evidence that a specific change in cigarette design, the introduction of filter ventilation holes, may be responsible for the increased risk of adenocarcinoma of the lung in smokers.

Eric Jacobs reduced

Eric M. Jacobs. Ph.D.

“Ventilation holes, engineered into cigarette filters by the tobacco industry starting in the 1960s, are present in nearly all modern cigarettes and are tied to a long history of deception. These holes allow air to be drawn in, resulting in cigarettes that have lower tar levels when measured by smoke-testing machines and that have been misleadingly marketed as “light” or “low-tar.” In fact, it has long been known that real-life smokers inhale similar amounts of tar when smoking cigarettes with ventilation holes. This occurs because smokers, often unconsciously, compensate for the ventilation holes by changing their smoking behavior, for example by taking by taking bigger puffs, in order to obtain the level of nicotine to which they are addicted.

“Among other evidence, the review describes studies showing that ventilation holes cause smokers to take bigger puffs, potentially inhaling carcinogen-containing smoke deeper into the parts of the lungs where adenocarcinoma typically arises.

“Thorough evidence reviews, like this one, help establish the scientific basis the Food and Drug Administration (FDA) needs to make sound decisions about the regulation of ventilation holes and other design features of tobacco products.”

Posted in Behavior, Environment, Lifestyle, Lung, Prevention, Research, Tobacco | 1 Comment

14: The Unmentioned Number in the Prostate Cancer/Coffee Story

CoffeeHeadlines across the Internet blared with the news over the past week that coffee could cut the risk of prostate cancer in half.  It was an irresistible headline. But just how reliable was the finding?

What if I told you it was based on just over a dozen cancer cases.

You read that right. All those headlines leaping out at you, based on 14 prostate cancers among heavy coffee drinkers.

To get some perspective on this, we turned to Eric Jacobs, Ph.D., Strategic Director of  Pharmacoepidemiology for the American Cancer Society. Here’s what he told us.

Eric Jacobs reduced

Eric M. Jacobs. Ph.D.

“While the 53% reduction in risk of prostate cancer in Italian men drinking more than 3 cups a day observed in this study is certainly eye-catching, it need to be interpreted cautiously.

“First, while the study design is generally sound, it is an observational study, not a randomized trial.  Second, it is based on small numbers, only 14 prostate cancer cases in men drinking more than 3 cups a day, so the amount of impact on prostate cancer risk, if any, is very uncertain.

“Third, this is one of many studies of coffee and prostate cancer. Previous studies have had mixed results, a meta-analysis of 9 previous cohort studies found about 10% lower risk of prostate cancer in men drinking moderate to high amounts of coffee, indicating that coffee drinking is unlikely to have a large effect on risk of prostate cancer.

The bottom line: there is not convincing evidence that coffee lowers risk of prostate cancer.”

So enjoy your coffee with your morning news reading. Just don’t rely on it to do much more than give your day a jump start.

Learn more about prostate cancer here.

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Panel Re-Opens the Door for PSA Screening in Men 55-69

14021677931_0a42428a45_bThe U.S. Preventive Services Task Force (USPSTF) has released draft recommendations for the use of prostate-specific antigen (PSA) screening for prostate cancer. The recommendation, which awaits public comment before being finalized, says the decision about whether to be screened for prostate cancer should be an individual one, moving from a “D” recommendation (not recommended) to a “C” recommendation for men ages 55 to 69. The group says screening men in this age group offers a small potential benefit of reducing the chance of dying of prostate cancer, but that many men will experience potential harms of screening, including false-positive results that require additional testing  as well as treatment complications, such as incontinence and impotence. We asked Otis Brawley for his thoughts regarding the newly proposed recommendations.

“This is a welcome change, one that puts USPSTF very much in line with the American Cancer Society as well the American College of Physicians and the American Urological Association.

“All of these organizations have moved to a recommendation that doctors discuss the harms and benefits of PSA screening with patients and let patients decide whether to be screened. Some groups, like the ACS, say that discussion should start at age 50; others, like the USPSTF, say age 55.

“The outcome from these groups’ recommendations is that some men will elect to be screened, and others will elect not to be screened; either decision should be supported.


Otis W. Brawley, M.D.

“The USPSTF made this change partly based on additional evidence about PSA screening’s potential to reduce prostate cancer spread and death. Importantly, the group also notes the increasing use of active surveillance, or watchful waiting, when PSA finds a low-risk cancer. That means fewer harms from surgery, which tips the scales towards the benefit side.

“While past screening recommendations were often a simple yes or no, an increasing understanding of cancer has led to more guidelines that now put the decision in the hands of the patient, with guidance and information from their doctor as well as from well-qualified medical/health related organizations.

The ACS’ last update of recommendations (in 2008) put perhaps the strongest emphasis on shared decision making of any organization to date, including providing decision making tools, as part of the update. While these can be complex issues for patients to navigate, it is imperative they play a central role since it is their lives that are affected.”


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The ‘Bad Luck’ Cancer Analysis, Part II

A new study revisits an analysis made by the same lab in 2015 about the role of random mutations on cancer. The analysis uses computer modeling to estimate how many cancers are the result of replication errors. The authors say their study provides a molecular explanation for the large and apparently unpreventable component of cancer risk that has long puzzled epidemiologists. A study by the same team a few years ago led to lots of debate about cancer prevention, and the role of ‘bad luck’ in cancer. Much of that was based on the original press release that said “two-thirds of adult cancer incidence across tissues can be explained primarily by ‘bad luck.’ ” Eventually, the release was edited to clarify that two-thirds of the variation across different cancers was due random mutations.

This time, the authors stress that their work “does not diminish the importance of primary prevention but emphasizes that not all cancers can be prevented by avoiding environmental risk factors.”

We asked Otis W. Brawley, M.D., chief medical officer,for his response to the new work.

“This study reaffirms what we have known about cancer for years, namely that many cancers occur not because of anything we did, but because of what we call ‘replication error.’ Replication error can be compared to a genetic game of telephone, where imperfections accumulate until the message is no longer correct. They use a hypothetical example that even people living on another planet where the environment is perfect, there would still be a baseline number of “unavoidable” cancers due to replication errors.


Otis W. Brawley, M.D.

“The study also reiterates the importance of two other major factors associated with cancer: heredity, and environment. Note that when epidemiologists talk about ‘environment,’ they’re referring not to exposure to toxins alone, but also to things like nutrition, physical activity, passive or direct smoking, sunlight, and other factors people are exposed to in their daily lives.

“The authors acknowledge that there is frequently a mix of these three influences: replication, heredity, and environment and that they can differ for different cancers under different circumstances.

“They calculated the impact of replication error by using a mathematical model to figure out how many times a cell would have to replicate before a random error would cause a cancer to start growing.

“Their initial report several years ago was met with lots of debate. This time, the authors explained the affect with caution and credibility, which should help clarify their conclusions in a way that will find a more receptive audience.

“The findings may lead to additional discussion of the role of ‘bad luck’ in cancer, but in fact the findings confirm something scientists have been talking about for a long time; that someone can do all the right things and still get cancer. This idea applies not only to people whose cancers are the result of replication error, but also to inherited genetic factors.

“While it would be easy to become fatalistic and think there’s nothing to be done about many cancers, in fact the paper reiterates the importance of primary prevention by avoiding environmental risk factors as well as ensuring everyone has access to proven early detection and screening, so we can find those cancers early and intervene in hopes of reducing their impact.”

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ACS Study Finds Colorectal Cancer Rates Have Risen Dramatically in Gen X and Millennials

A groundbreaking study by American Cancer Society epidemiologist Rebecca Siegel, MPH finds that people born in the United States in 1990 have double the risk of colon cancer and quadruple the risk of rectal cancer compared to those born around 1950, when colorectal cancer risk was lowest.

polypThe study appears in the Journal of the National Cancer Institute, and  finds colorectal cancer (CRC) incidence rates are rising in young and middle-aged adults, including people in their early 50s, with rectal cancer rates increasing particularly fast. As a result, three in ten rectal cancer diagnoses are now in patients younger than age 55.

Overall, CRC incidence rates have been declining in the United States since the mid-1980s, with steeper drops in the most recent decade driven by screening. Recently though, studies have reported increasing CRC incidence in adults under 50, for whom screening is not recommended for those at average risk. However, these studies did not examine incidence rates by 5-year age group or year of birth, so the scope of the increasing trend had not been fully assessed.

To get a better understanding, investigators led by Ms. Siegel used “age-period-cohort modeling,” a quantitative tool designed to disentangle factors that influence all ages, such as changes in medical practice, from factors that vary by generation, typically due to changes in behavior. They conducted a retrospective study of all patients 20 years and older diagnosed with invasive CRC from 1974 through 2013 in the nine oldest Surveillance, Epidemiology, and End Results (SEER) program registries. There were 490,305 cases included in the analysis.

The study found that after decreasing since 1974, colon cancer incidence rates increased by 1% to 2% per year from the mid-1980s through 2013 in adults ages 20 to 39. In adults 40 to 54, rates increased by 0.5% to 1% per year from the mid-1990s through 2013.

Rectal cancer incidence rates have been increasing even longer and faster than colon cancer, rising about 3% per year from 1974 to 2013 in adults ages 20 to 29 and from 1980 to 2013 in adults ages 30 to 39. In adults ages 40 to 54, rectal cancer rates increased by 2% per year from the 1990s to 2013. In contrast, rectal cancer rates in adults age 55 and older have generally been declining for at least 40 years, well before widespread screening.

Opposing trends in young versus older adults over two decades have closed a previously wide gap in disease risk for people in their early 50s compared to those in their late 50s. Both colon and rectal cancer incidence rates in adults ages 50 to 54 were half those in adults ages 55 to 59 in the early 1990s, but in 2012 to 2013, they were just 12.4% lower for colon and were equal for rectal cancer.


Rebecca Siegel, MPH

“Trends in young people are a bellwether for the future disease burden,” said Siegel. “Our finding that colorectal cancer risk for millennials has escalated back to the level of those born in the late 1800s is very sobering. Educational campaigns are needed to alert clinicians and the general public about this increase to help reduce delays in diagnosis, which are so prevalent in young people, but also to encourage healthier eating and more active lifestyles to try to reverse this trend.”

In addition, the authors suggest that the age to initiate screening people at average risk may need to be reconsidered. They point out that in 2013, 10,400 new cases of CRC were diagnosed in people in their 40s, with an additional 12,800 cases diagnosed in people in their early 50s. “These numbers are similar to the total number of cervical cancers diagnosed, for which we recommend screening for the 95 million women ages 21 to 65 years,” said Siegel.

That prompts the question: Is ACS going to change its guidelines? For some answers on that, we went to Otis Brawley, M.D., chief medical officer.

“There is increasing evidence, some of it published by ACS investigators, that colorectal cancer is increasing in people younger than age 55 years. This new data will be examined by our independent guidelines development group to review whether a change in our screening recommendations is warranted, particularly since screening can prevent colorectal cancer, averting substantial morbidity and mortality during the most productive years of life.


Otis W. Brawley, M.D.

“Guidelines from the ACS and others are designed to catch as many cancers as possible while minimizing the adverse effects associated with screening those with low rates of disease. No organization’s guideline is designed to catch every cancer. This often becomes in issue in younger populations, where cancers are more rare, and naturally of great concern.

“Every screening recommendation involves weighing the potential benefits against the harms associated with procedures that come as a result of screening. We need to be sure we’re doing more good than harm.

“The risk of colorectal cancer is increasing for every generation born since the 1950s, something we suspect is due to the complex relationship between obesity, an unhealthy diet, and lack of physical activity.

“No one study is enough to change our guidelines. We continue to track this issue in an effort to make sure our screening recommendations reflect the latest evidence.

“It is important to note that when there is a family history of early onset colorectal cancers, the ACS and others support beginning screening at a younger age.”

You can read more about what we know about colorectal cancer risk on

Article: Colorectal Cancer Incidence Patterns in the United States, 1974-2013; J Natl Cancer Inst (2017) 109(8): DOI: 10.1093/jnci/djw322

Posted in Colorectal, Prevention, Screening, Society news | 1 Comment