Category Archives: Prostate Cancer

Racial Differences in Prostate Cancer

Prostate Cancer, Prostate Cancer, , , ,

Meg Seymour, PhD: National Center for Health Research

About 13% of men will develop prostate cancer during their lifetime, and about 2-3% of men will die from it.[1] After lung cancer, prostate cancer is the leading cause of cancer deaths in men[2], and older men are more likely to get prostate cancer then younger men.[1]

There are known racial differences as well: Black men are 1.5 times more likely to get prostate cancer than White or Latino men, and 3 times more likely to get prostate cancer than Asians and Pacific Islanders.[3,4] On average, Black men get prostate cancer a younger ages than other men, and their cancer is often more aggressive and more advanced when it is discovered.[1] Black men are also more than twice as likely to die from prostate cancer than men from other races.[1] 

This article will discuss the known racial differences in the screening, treatment, and outcomes of prostate cancer in the United States, as well as why these differences may exist. Note that many of the differences that have been studied compare Black and White men, and data about men from other races and ethnicities are more limited.

Differences in Screening

One of the main methods of screening for prostate cancer is a blood test that measures levels of prostate-specific antigen (PSA). PSA tests alone cannot tell if someone has cancer, but high levels of PSA might lead to further testing, like a biopsy. Another method of testing is the digital rectal exam, in which a doctor inserts a (gloved and lubricated) finger into a patient’s rectum to feel the prostate for bumps or hard areas, which might be cancer. 

As of 2018, the United States Preventive Services Task Force does not recommend prostate cancer screening for men ages 70 and over.[5] For men ages 55 to 69, they recommend that PSA screening should be an individual choice, based on factors such as family history or patient preference. For more information about prostate cancer screening and the recommendations for it, you can read this article.

If the results of a PSA test or digital rectal exam leads a doctor to suspect cancer, it can lead to a biopsy. A biopsy is when a small sample of tissue is removed and examined under a microscope for cancer cells.[6]

A 2017 article in a medical journal found that overall, non-Hispanic White men were slightly more likely to undergo PSA screening than Black men. This was a trend for the United States overall, but analysis by individual states showed that screening rates were actually higher for Black men in some states.[7] More recently, a 2020 study showed that between 2014 and 2018, Black men underwent prostate cancer screening at either a slightly lower rate than White men or at the same rate.[8] The study authors note that Black men need to be more intensively screened because they are more likely to get prostate cancer.  

A study presented at the 2021 meeting of the American Society of Clinical Oncology included over 4,000 Black men ages 40-55 who had been diagnosed with prostate cancer.[9] The study found that men who had an average of 3 PSA tests prior to their diagnosis were less likely to have metastatic disease than men who had an average of 0.5 PSA tests at the time of their diagnosis. Only 1.4% of the men who had been screened an average of 3 times had metastatic disease, compared with 4.2% of the men who had the least screening. Higher rates of PSA screening prior to diagnosis was also associated with a 25% reduction in the risk of dying from prostate cancer. The study suggests that more frequent PSA screening is associated with better outcomes among younger Black men.

Accuracy of screening also varied by race. A 2018 study found that although Black men were slightly more likely to have a false positive from their PSA screening, they were less likely to have a false positive from a digital rectal exam. Further, Black men were more likely than White men to have aggressive tumors and cancer that has metastasized, which means that it has spread to other body parts.[10] 

Differences in Treatment

There are numerous treatment options for prostate cancer, such as surgery, radiation, hormone therapy, and what are called watchful waiting and active surveillance. These treatment choices also vary by race.  

Active surveillance means that no specific treatment like surgery or a drug is used. Instead, a doctor closely monitors the cancer to see if it grows, using regular PSA tests, digital rectal exams, and biopsies. This option may be used if a man’s cancer is small, localized, or expected to grow slowly, so that he is not immediately treated with aggressive treatments that may have side effects.[11] Active surveillance is used for as many as 33% of men diagnosed with prostate cancer,[12] but it is not equally used among all men in the United States. A 2020 study found that although Black and White men receive active monitoring at the same rate, Hispanic men were less likely to receive it.[12] The researchers could not identify why this ethnic difference exists, but they noted that it could have to do with factors such as patient preferences or how often the option is offered by doctors.

Watchful waiting (also called observation) is slightly different from active surveillance. It involves less intensive follow-up, such as fewer tests. Instead, the patient’s doctor decides to wait and see if symptoms change. For many men, prostate cancer grows so slowly that a man might die of other causes before he would die of the cancer, so aggressive treatment is not needed. Treatments for prostate cancer can cause undesired side effects, such as incontinence and impotence, so many men may choose active surveillance or watchful waiting, if their cancer is considered low-risk enough.  

Definitive therapy refers to radiation treatment or surgical removal of the prostate. Both procedures can have side effects such as erectile dysfunction and impotence.[13] A 2017 study looked at over 300,000 men who were diagnosed with localized prostate cancer and compared which men received definitive treatments, such as surgery, to which men received no treatment, such as men undergoing active surveillance. The study found that although White and Asian men received definitive treatment at about the same rate, Hispanic and Black men were less likely to receive it than White men were.[14] In the study, Black men with high risk prostate cancer were actually less likely to receive definitive therapy than White men with lower risk disease. Although Black men were likely to be on active surveillance, Black men on active surveillance are actually monitored less than White men on active surveillance. The researchers argue that Black men might be more likely than White men to benefit from definitive therapy, so they are concerned by the result that they are less likely to receive it. 

A 2016 study looked at surgical treatments for localized prostate cancer in men insured by Medicare. The researchers found that, on average, Black patients experienced a longer delay between diagnosis and treatment, and had more postoperative complications than White patients.[15] Research on men with metastatic prostate cancer has also found that Black men treated with the drugs docetaxel, abiraterone acetate, or enzalutamide have similar or even better outcomes to other men.[16] Researchers question why Black men have overall higher mortality rates from prostate cancer than other men. For example, is the higher death rate among Black men because they often have more advanced cancer when it is discovered, because their cancer is more aggressive, or because there is unequal access to treatments?

Why Do These Differences Exist?

Some people have suggested that racial differences in prostate cancer outcomes are because White men are, on average, of higher socioeconomic status than Black men. However, research has found that comparing men of the same socioeconomic status level, cancer screening was still more common among White men and detection of cancer was also earlier for White men.[17]

Researchers have suggested that differences in survival by race may be because Black men are more likely to be diagnosed at advanced stages of their cancer, when treatment options are more limited and can be less effective.[17] They are also more likely to have comorbid illnesses, such as diabetes and hypertension, which could affect survival rates.

A 2016 study found that, among men with localized prostate cancer, when researchers adjust for differences like at what stage a man’s cancer was diagnosed and what treatment he received, survival rates are equal across all races of men.[15] It is possible that the differences in cancer survival between races are due to racial differences in access to care.

There is an ongoing need for research into the causes of racial disparities in prostate cancer outcomes. 

The Bottom Line

Prostate cancer is a common form of cancer in men, and although it does not always need to be actively treated, it is one of the leading cancer killers. Black men are disproportionately affected. They are often diagnosed at younger ages, with more advanced stages of cancer, with more aggressive cancers, and they may be more likely to need screening. Further research is needed to understand the causes in racial differences in prostate cancer, but at least some of the differences in rates of survival between Black and White men may be due to differences in access to medical care.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

The National Center for Health Research is a nonprofit, nonpartisan research, education and advocacy organization that analyzes and explains the latest medical research and speaks out on policies and programs. We do not accept funding from pharmaceutical companies or medical device manufacturers. Find out how you can support us here.

References 

  1.     Centers for Disease Control and Prevention. Who Is at Risk for Prostate Cancer?. Cdc.gov. https://www.cdc.gov/cancer/prostate/basic_info/risk_factors.htm. Updated August 2020. 
  2.     Siegel DA, O’Neil ME, Richards TB, Dowling NF, Weir HK. Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity — United States, 2001–2017. MMWR Morbidity and Mortality Weekly Report. 2020;69:1473–1480. 
  3.     Borno H, George DJ, Schnipper LE, Cavalli F, Cerny T, Gillessen S. All men are created equal: addressing disparities in prostate cancer care. American Society of Clinical Oncology Educational Book. 2019 May 17;39:302-8.
  4.     Dobbs RW, Malhotra NR, Abern MR, Moreira DM. Prostate cancer disparities in Hispanics by country of origin: a nationwide population-based analysis. Prostate Cancer and Prostatic Diseases. 2019 Mar;22(1):159-67.
  5.     Fenton JJ, Weyrich MS, Durbin S, Liu Y, Bang H, Melnikow J. Prostate-specific antigen–based screening for prostate cancer: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018 May 8;319(18):1914-31.
  6.     American Cancer Society. Tests to Diagnose and Stage Prostate Cancer. Cancer.org. https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/how-diagnosed.html. Updated December 2020. 
  7.     Jindal T, Kachroo N, Sammon J, Dalela D, Sood A, Vetterlein MW, Karabon P, Jeong W, Menon M, Trinh QD, Abdollah F. Racial differences in prostate-specific antigen–based prostate cancer screening: state-by-state and region-by-region analyses. Urologic Oncology: Seminars and Original Investigations. 2017; 35(7):460-e9. 
  8.     Kearns JT, Adeyemi O, Anderson WE, Hetherington TC, Taylor YJ, Zhu J, Burgess EF, Gaston KE. Contemporary racial disparities in PSA screening in a large, integrated health care system. 2020; 38(6): 308-308. 
  9.   Bassett M. Vaccination, Screening Succeeds in Cervical and Prostate Cancers. MedPageToday. https://www.medpagetoday.com/meetingcoverage/asco/92688. May 19, 2021. 
  10.     Miller EA, Pinsky PF, Black A, Andriole GL, Pierre‐Victor D. Secondary prostate cancer screening outcomes by race in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial. The Prostate. 2018; 78(11):830-8.
  11. American Cancer Society. Observation or Active Surveillance for Prostate Cancer. Cancer.org. https://www.cancer.org/cancer/prostate-cancer/treating/watchful-waiting.html. Updated August 2019. 
  12. Washington SL, Jeong CW, Lonergan PE, Herlemann A, Gomez SL, Carroll PR, Cooperberg MR. Regional Variation in Active Surveillance for Low-Risk Prostate Cancer in the US. JAMA Network Open. 2020; 3(12):e2031349-.
  13. Tracy CR. Prostate Cancer Treatment & Management. Emedicine.medscape.com,. https://emedicine.medscape.com/article/1967731-treatment. Updated February 2, 2021. 
  14. Moses KA, Orom H, Brasel A, Gaddy J, Underwood III W. Racial/ethnic disparity in treatment for prostate cancer: does cancer severity matter?. Urology. 2017;99:76-83.
  15. Schmid M, Meyer CP, Reznor G, Choueiri TK, Hanske J, Sammon JD, Abdollah F, Chun FK, Kibel AS, Tucker-Seeley RD, Kantoff PW. Racial differences in the surgical care of Medicare beneficiaries with localized prostate cancer. JAMA Oncology. 2016;2(1):85-93.
  16. Hahn AW, Bilen MA, Agarwal N. Successful Recruitment of Black Men to Prostate Cancer Clinical Trials—A Lesson in Achievement. JAMA Network Open. 2021;4(1):e2034652-.)
  17. Di Pietro G, Chornokur G, Kumar NB, Davis C, Park JY. Racial differences in the diagnosis and treatment of prostate cancer. International Neurourology Journal. 2016;20(Suppl 2):S112.

NCHR’s Testimony to FDA on TOOKAD to Treat Low-Risk Prostate Cancer

Prostate Cancer, Testimony & Briefings, ,

Diana Zuckerman, National Center for Health Research, February 26, 2020

Thank you for the opportunity to speak today.  I am Dr. Diana Zuckerman, president of the National Center for Health Research. Our center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.

Although active surveillance is recommended for many patients with low-risk prostate cancer, some patients prefer treatment and that can be a reasonable choice as long as the treatment has a meaningful benefit and does not increase patients’ harms. However, the clinical data for TOOKAD that we are discussing today do not clearly demonstrate that its benefits outweigh its risks – efficacy is uncertain, particularly for U.S. patients, and the drug has the well-known very negative side effects typical of prostate cancer treatments.  

There are 5 major problems with the data, and the FDA did an excellent job of expressing their concerns:

#1.  There was only 1 clinical trial. Replication is the key to science, and effective treatments are available for prostate cancer, so the FDA should not approve a new treatment based on just one study.

#2.  This one trial took place in Europe, and 99.8% of participants were white.  Five patients – not 5% but only 5 men — were not white. Given the higher percentage of African American men who die of prostate cancer, this lack of diversity should not be considered acceptable, unless the FDA is considering approving this product for white men only.

#3. The accuracy of detecting cancer is one major problem. The data showed a high false negative rate. 13.5% of those in the active surveillance arm had a negative biopsy after 2 years. Since it is unlikely that the cancer would spontaneously disappear, this probably reflects false positives in the original diagnosis or false negatives in the post-test. This high false negative rate raises major concerns about the accuracy of biopsies in the treatment arm and at baseline. 

#4. Further, there was a large amount of missing data regarding biopsies at 24 months. Unfortunately, 18.4% of the patients in the treatment arm and 41.5% of those in the active surveillance arm were missing these crucial pieces of information regarding efficacy.  That makes it impossible to draw conclusions based on this one study. 

 #5. The trial was open-label, meaning patients as well as those collecting the data knew whether a particular patient was receiving the treatment or active surveillance. The decision to pursue definitive therapy  — such as surgery — was a subjective decision. Wouldn’t active surveillance patients be more likely to choose treatments later. Also, when biopsy results were uncertain, pathologists may have been biased by their knowledge of whether or not a patient was assigned to the treatment group. 

The FDA held a workshop in September 2018 to discuss issues related to clinical trials of novel treatments for localized prostate cancer.  They concluded that treatment endpoints might be clinically meaningful only if 1) the patients using the new therapy were less likely to undergo subsequent treatment (such as surgery), 2) there was an overall reduction in adverse events, and 3) there was no reduction in long-term cancer control.  However, in this trial, these criteria were not met. 95% of those treated with TOOKAD had adverse event in the weeks after treatment compared to 55% of the men on active surveillance. For many men these problems continued 2 years after treatment, when 34% continued to have urinary problems compared to 16% with active surveillance. Two years after treatment, 38% of patients treated with TOOKAD had erectile dysfunction, compared with 12% of those assigned to active surveillance. In other words, erectile dysfunction was 3x as prevalent among those treated with TOOKAD.

The long-term complications of the treatment that are unclear.  In addition to the urinary problems and ED that might be worse for those who are subsequently treated with surgery, it may be more difficult to obtain accurate biopsies. 

The American Urological Association recommends active surveillance as the best available treatment for low-risk prostate cancer patients, and the data clearly support that recommendation.  We understand that the fear of cancer can persuade men to seek treatment, but if so they should not be bamboozled by ads to choose a product that may have no benefits for them but that does have clear risks of erectile dysfunction and urinary problems. If the FDA thinks this product might have a useful benefit, they should require at least one double-blind study – preferably two – since the treatment does not involved surgery and is therefore easier to blind.  The studies should also include a patient population that represents the diversity of men with prostate cancer. There is no need to rush to approve this particular treatment based on a single, open label trial with endpoints of questionable clinical relevance and problems with inaccurate diagnoses. Better research needs to be completed before approval because the sponsor did not comply with FDA’s recommendations for the study and was even less likely to do so after the product is approved.   

The Oncologic Drugs Advisory Committee voted 13 to 2 against approval of TOOKAD to treat low-risk prostate cancer.

Are Annual Prostate Cancer Screenings Necessary? Should Early Stage Prostate Cancer Be Treated?

Prevention, Prostate Cancer, Prostate Cancer,
By Krystle Seu, Dana Casciotti, PhD, Brandel France de Bravo, MPH, Mingxin Chen, MHS, and Nicholas Jury, PhD

Although usually not fatal, prostate cancer is second leading cause of cancer deaths for men in the United States, after lung cancer.[1] One in every eight men will be diagnosed with prostate cancer in his lifetime.1 Most cases are in men 65 and older, and most deaths occur in men 75 and older.2 Annual screenings would seem to be an important way to prevent prostate cancer.  But there is a hot debate within the medical community: Do routine prostate cancer screenings lead to unnecessary treatment that does more harm than good?

Should I Get Screened?

Diagnostic tests for prostate cancer are recommended for any man who has symptoms of prostate cancer, such as pain or changes in urination. Men over the age of 50 who have no symptoms sometimes undergo screening tests. In May 2012, the U.S. Preventive Services Task Force recommended against prostate-specific antigen (PSA) screening tests for men of any age.3 However, in May 2018, the Task Force revised their recommendation, stating that men ages 55-69 years old should talk to their doctor about the potential benefits and harms of PSA screening. The USPSTF continues to recommend against PSA screening in men ages 70 and older.4

What about other methods of screening, like digital rectal exams, which are usually done together with PSA testing? The Task Force continues to conclude that they tend to do more harm than good.

The U.S. Preventive Services Task Force is an independent group of medical professionals that reviews all evidence on preventive health care services. In 2008, the Task Force had said screening was not recommended for men over 75, but wasn’t sure about its value for men younger than 75.5 In 2009, the American Urological Association issued new guidelines saying that annual screening was no longer recommended.6

The reason why these experts concluded that screening was rarely necessary is that prostate cancer grows very slowly.  Even without treatment, many men with prostate cancer will live with the disease until they eventually die of some other, unrelated cause.  However, there is concern that without screening, some men are being diagnosed with prostate cancer when it is more advanced and more likely to be fatal.  While annual screening seems unnecessary, this article will help you decide whether occasional screening is a good idea for you.

Types of Prostate Cancer Screening: PSA Blood Tests and Digital Rectal Exams

Prostate cancer occurs when cells create small tumors in the prostate gland, which is an important part of the male reproductive system. Screening can be performed quickly and easily in a physician’s office using two tests: the prostate-specific-antigen (PSA) blood test, and the digital rectal exam (DRE), a manual exam of the prostate area.

Most screening tests are not 100% accurate, but these prostate tests are especially inaccurate.  Most men with a high PSA level (>4ng/mL) do not have prostate cancer (this is known as a false positive), and some men with prostate cancer have a low PSA level (this is called a false negative). The DRE also results in many false positives and false negatives. Using both screening methods together will miss fewer cancers but also increases the number of false positives, which can lead to more testing (usually biopsies of the prostate) and possibly result in medical complications. A biopsy to determine if there is a cancerous growth in the prostate involves inserting a needle, usually through the rectum, to remove a small sample of prostate tissue.

PSA Velocity

Researchers are also trying to determine if other types of PSA testing might be more accurate in detecting prostate cancer, such as changes in PSA levels when a man has multiple tests over time. The rate of change of PSA level from one test to the next is known as “PSA velocity.”

One study examined if PSA velocity could improve cancer detection compared to standard PSA and DRE screening tests.7 Because men with high PSA levels and positive DRE results typically undergo prostate biopsies to determine the presence of cancer, this study evaluated if PSA velocity helped detect cancer in men with low PSA and negative DRE results. Over 5,500 men were included in the study and men with high PSA velocity-almost 1 in 7 men-were biopsied. The researchers found that doing biopsies on the basis of high PSA velocity in the absence of a high PSA or positive DRE would lead to a large number of biopsies but would not improve cancer detection.

What Recent Research Tells Us About Prostate Cancer Screening

Depending on how often screening is done, it may help reduce the chances of dying of prostate cancer, but the research indicates that the vast majority of men with prostate cancer die of a different cause, even if they are not treated.

Several years ago, two major research studies have tried to shed light on the value of regular screening: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Trial of Screening for Prostate Cancer (ERSPC).8 The PLCO studied 76,000 men, aged 55-74, for 7-10 years and found that the death rate from prostate cancer was low, and that it did not differ between the men who were screened every year for the first six years of the study and those who received their usual care (which ranged from no screening to occasional screening).9 For most of the patients, “usual care” included at least one screening during the first seven years of the study. There were also no significant differences in overall death rates between the groups. Although the randomized portion of the study was completed in 2006, researchers are still studying the patients to see how long they live.10

The European study (ERSPC) included 182,000 men, ranging from 50 to 74 years old, from seven different European countries.11 In these countries, “regular screening” is usually every 4 years, although it is every 2 years in Sweden. Those men were compared to men of the same age who did not get any prostate cancer screening. After the men were studied for an average of 13 years, the researchers found that the patients who had PSA screening were 27% less likely to die of prostate cancer.8 However, they did not live longer than the other men, because they died of other causes.

A follow-up to the ERSPC study, which tracked the men for an average of 11 years, found an even greater reduction in prostate cancer deaths-29% over the longer follow-up period.12 To prevent 1 death from prostate cancer, the program needed to screen 1,055 men and treat 37 men.  More important, although deaths from prostate cancer were lower in the PSA screened group, there were no differences in overall mortality between the two groups.  In other words, the PSA screening reduced deaths from prostate cancer but did not save lives because those men were more likely to die from other causes.

Recent updates to a 2010 meta-analysis (which means researchers “pooled” data from many different but comparable studies) of six randomized, controlled prostate cancer screening trials (including the PLCO and ERSPC studies) further support the U.S. Preventive Services Task Force recommendations. Analysis of data on almost 330,000 men showed no significant difference in the risk of death from prostate cancer between the men who received PSA screenings and those who did not.13

A United Kingdom study published in 2018 in the prestigious medical journal JAMA involved over 160,000 men between the ages of 50 to 59 years. The study found that a one-time PSA screen increased the chances of diagnosing prostate cancer, but did not change the chances of dying from prostate cancer. Over a 10-year period, about 4.3% of men who had a one-time PSA test were diagnosed with prostate cancer compared to about 3.6% of men who did not have a PSA screen. The one-time PSA screen was able to detect prostate cancers that were lower grade and less likely to be dangerous.

Importantly, there was no evidence that having a PSA screen test saved lives. In men who were diagnosed with prostate cancer, the chances of dying from the prostate cancer within 10-years of diagnosis were about 3 in 10,000 (that’s less than half of a percent), and that was the case whether the men had a PSA screening or not. This means that a PSA test may detect more prostate cancers, but these are likely cancers that would not have been harmful. This study does not show that one-time screening with PSA would be helpful, and it could be harmful. The researchers have planned to look at these issues more closely in a longer term study.14

Benefits and Harms of Screening

The benefit of screening is that the disease is often curable with early detection (90% or better).  Common treatments like surgery or radiation aim to remove or kill all cancerous cells in the prostate.  If the cancer spreads beyond the prostate before it is treated, it is often fatal.  However, the cancer usually grows so slowly that it is often equally safe to wait until there are symptoms before attempting to diagnose prostate cancer. Symptoms of prostate cancer might include urinary problems, difficulty having an erection, or blood in the urine or semen.

The harms of screening include 1) inaccurate results leading to unnecessary biopsies and complications, and 2) complications from unnecessary treatment. Even if a man has prostate cancer, if he does not have symptoms he may not need to be treated. Experts estimate that between 18% and 85% of prostate cancers detected by these screening tests would never become advanced enough to harm the patient.  This wide range of uncertainty, however (is it less than 1 out of 5 or more than 4 out of 5?) just adds to the confusion.

Unnecessary treatment costs a lot of money, but the main concern is the complications, which include serious and long-lasting problems, such as urinary incontinence and erectile dysfunction.15

Long before the Task Force made its recommendation, many doctors and patients questioned whether annual prostate cancer screenings were a good idea, since the disease is rarely fatal. Many also question whether treating early prostate cancer, the kind of prostate cancer screening tests mostly find, is a good idea. Treating early prostate cancer does not appear to help men live longer, and for many it drastically reduces their quality of life.

Doctors and scientists are searching for better tests for prostate cancer detection. Many experts believe that a family history of prostate cancer or other cancers should influence how often a man chooses to get PSA screening.  However, the studies described below, which led to the Task Force’s recommendation against PSA screening, suggest that annual screenings for all men are not a good idea.

Is Surgery Effective for Men with Early-Stage Prostate Cancer?

When they hear the word “cancer,” many men want it treated immediately no matter how slow it is growing or how unlikely it is to be fatal. The question is: if found in its early stages, should prostate cancer be treated?  The answer to that question has changed in the last decade, with approximately 60% of U.S. men with low-risk prostate cancer choosing “active surveillance” in 2018, compared to less than 20% eight years earlier.16 Active surveillance, also called “watchful waiting” includes careful monitoring of the cancer by the physician, rather than surgery, radiation, or other treatment. The percentage of men choosing monitoring instead of treatment is even higher in Sweden and Australia.

The evidence supporting active surveillance is more than a decade old. In July 2012, a study by researchers at the Department of Veterans Affairs was published in the New England Journal of Medicine, examining the effectiveness of surgery in men with early-stage prostate cancer.17 Known as the Prostate Cancer Intervention versus Observation Trial, or PIVOT, the study compared surgical removal of the prostate with no prostate cancer treatment. The 731 men who participated in the study, with an average age of 67, were randomly assigned to one of the two groups and followed for 8 to 15 years. All the men were enrolled between 1994 and 2002, with a final check-up taking place in 2010. Men in both groups went to the doctor every six months during the study, and men in the observation-only group were offered palliative therapy (which focuses on reducing suffering) or chemotherapy to relieve symptoms due to the cancer spreading to other parts of the body. Neither therapy can eliminate the cancer and, therefore, are not treatments.

The findings suggest that prostate cancer surgery does not save the lives of men with early-stage prostate cancer. Only 7% of the participants died of prostate cancer or from treatment during the study: 21 or 5.8% of those had their prostate removed and 31 (8.4%) who did not undergo surgery. The difference between the surgery and observation groups was not statistically significant, which means that the smaller number who died in the surgery group could have been due to chance. The prostate cancer spread to the bone in 4.7% of the surgery patients and to 10.6% of the observation or no-treatment group. Even when cause of death wasn’t limited to prostate cancer, the two groups died at about the same rate: 47% of the men who had surgery died during the study period as compared with 50% in the observation group.

The only men who benefited from the surgery were those with a PSA of 10 ng per milliliter or higher and men with riskier tumors: their overall risk of dying during the study period — not necessarily from prostate cancer — was lower than in the observation group. Surgery reduced the risk of dying from any cause by 13.2% among men with a PSA of 10 ng per milliliter or higher. For men with intermediate risk tumors (determined by a PSA value of 10.1 to 20.0 ng per milliliter, a score of 7 on the Gleason scale, or a stage T2b tumor), surgery reduced their risk of dying by 12.6%, but for men with high risk tumors, the reduction in risk by 6.7% was not statistically significant. That means it could have happened by chance.

In September 2016, the prestigious New England Journal of Medicine published a 10-year study by researchers from University of Oxford, which provided solid evidence that neither surgery nor radiation treatments save lives.18 The study compared the death rates of three patient groups: surgery, radiation, and active monitoring, which is sometimes called active surveillance. Between 1999 and 2009, the study randomly assigned 1643 men with diagnosed prostate cancer to the three groups to receive radical surgery (553 men), radical radiotherapy (545), or active monitoring (545). Unlike the PIVOT study, patients in the “active monitoring group” underwent tests to determine if their prostate cancer had progressed; these were conducted every 3 months for the first year, and every 6 to 12 months after that. The patients had an average (median) of 10 years of follow-up.

At the final check-up, 169 men had died, and there was no significant difference among the three groups of prostate cancer patients. Only 17 of these were deaths from prostate cancer: 5 in the surgery group, 4 in the radiotherapy group, and 8 in the active-monitoring group. However, prostate cancer was more likely to progress or spread in the group of men who were monitored rather than treated.

This 2016 study was the first to compare the effectiveness of surgery, radiotherapy and active monitoring. The findings suggest that treatment does not improve the chances of a man living longer, since most of the men will be dying of other causes rather than prostate cancer. Since prostate cancer treatment can cause serious side effects such as erectile dysfunction and incontinence, active monitoring is now recognized as a reasonable option. In fact, due to studies like this, active monitoring (also called active surveillance) is considered the preferred option for most men with low-risk prostate cancer.19 The number of men in the United States who receive active monitoring instead of active treatment has been increasing in recent years. In 2010, only 13% of men with prostate cancer received active monitoring, compared to 33% of men in 2015.

One small study found that high intensity exercise may be beneficial for men undergoing active monitoring. The study found that men who ran on a treadmill for 40 minutes, 3 times a week for 12 weeks had lower PSA levels after the 12 weeks than before they started the exercise regimen, but that was not true for men who did not do the exercise regimen. The researchers note that exercise increases cardiorespiratory fitness, which could inhibit the progression of prostate cancer for men on active monitoring.20

Unfortunately, a 2020 study of over 80,000 men with low risk, localized prostate cancer found that active monitoring is not equally common across all regions of the United States and across all men.19 Men with Medicaid, as well as men living in counties where fewer residents have a college education, were less likely to receive active monitoring. Although rates of active monitoring were the same for Black and White men, the study found that Hispanic men were less likely to receive it. The researchers could not identify why this ethnic difference exists, but they suggested that it may be due to factors such as differences in how often the option is offered by doctors and patients’ preferences. The study also found that single men were more likely to use active monitoring than married men.

Since prostate cancer treatment can cause serious side effects such as erectile dysfunction and incontinence, active monitoring seems to be a reasonable option for many men, especially those with lower risk prostate cancers.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

The National Center for Health Research is a nonprofit, nonpartisan research, education and advocacy organization that analyzes and explains the latest medical research and speaks out on policies and programs. We do not accept funding from pharmaceutical companies or medical device manufacturers. Find out how you can support us here.

References

  1. American Cancer Society. Key Statistics for Prostate Cancer. Cancer.org. https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Updated January 2021. 
  2. National Cancer Institute. Cancer Stat Facts: Prostate Cancer. Seer.cancer.gov. https://seer.cancer.gov/statfacts/html/prost.html. 
  3. Moyer VA. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Annals of Internal Medicine. 2012;157(2):120-34.
  4. Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, Davidson KW, Doubeni CA, Ebell M, Epling JW, Kemper AR, Krist AH. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018 May 8;319(18):1901-13.
  5. Calonge N, Petitti DB, Dewitt TG, Dietrich AJ, Gregory KD, Harris R, Isham GJ, Lefevre ML, Leipzig R, Loveland-Cherry C, Marion LN. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Annals of Internal Medicine. 2008; 149(3):185-91.
  6. Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, Kuban DA, Sartor AO, Stanford JL, Zietman A, Carroll P. Prostate specific antigen best practice statement: 2009 update. The Journal of Urology. 2009; 182(5):2232-41.
  7. Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM. An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection. Journal of the National Cancer Institute. 2011; 103(6):462-9.
  8. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, Kwiatkowski M, Lujan M, Määttänen L, Lilja H, Denis LJ. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014; 384(9959):2027-35.
  9. Andriole GL, Crawford ED, Grubb III RL, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine. 2009; 360(13):1310-9.
  10. National Cancer Institute. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Prevention.cancer.gov. https://prevention.cancer.gov/major-programs/prostate-lung-colorectal-and-ovarian-cancer-screening-trial.
  11. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine. 2009; 360(13):1320-8.
  12. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ. Prostate-cancer mortality at 11 years of follow-up. New England Journal of Medicine. 2012; 366(11):981-90.
  13. Djulbegovic M, Neuberger MM, Dahm P. Prostate-cancer mortality after PSA screening. The New England Journal of Medicine. 2012; 366(23):2228-9.
  14. Barry MJ. Screening for prostate cancer: is the third trial the charm?. JAMA. 2018; 319(9):868-9.
  15. Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, Lin X, Greenfield TK, Litwin MS, Saigal CS, Mahadevan A. Quality of life and satisfaction with outcome among prostate-cancer survivors. New England Journal of Medicine. 2008; 358(12):1250-61.
  16. Al Hussein Al Awamlh B, Barocas DA, Zhu A, et al. Use of Active Surveillance vs Definitive Treatment Among Men With Low- and Favorable Intermediate–Risk Prostate Cancer in the US Between 2010 and 2018. JAMA Intern Med. 2023; doi:10.1001/jamainternmed.2022.7100
  17. Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, Gingrich JR, Wei JT, Gilhooly P, Grob BM, Nsouli I. Radical prostatectomy versus observation for localized prostate cancer. New England Journal of Medicine. 2012; 367:203-13.
  18. Hamdy FC, Donovan JL, Lane J, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. New England Journal of Medicine. 2016; 375:1415-24.
  19. Washington SL, Jeong CW, Lonergan PE, Herlemann A, Gomez SL, Carroll PR, Cooperberg MR. Regional Variation in Active Surveillance for Low-Risk Prostate Cancer in the US. JAMA Network Open. 2020; 3(12):e2031349-.
  20. Kang DW, Fairey AS, Boulé NG, Field CJ, Wharton SA, Courneya KS. Effects of exercise on cardiorespiratory fitness and biochemical progression in men with localized prostate cancer under active surveillance: the erase randomized clinical trial. JAMA Oncology. 2021 Oct 1;7(10):1487-95.

Can Aspirin Prevent Cancer?

Breast Cancer, Colon Cancer, news-you-can-use, Prevention, Prostate Cancer
Diana Zuckerman, PhD: Cancer Prevention and Treatment Fund

Many Americans take low-dose aspirin, also called baby aspirin, to prevent cancer and heart disease. Taking daily aspirin increases the risk of bleeding, so it is important to compare the risks and benefits.  By 2019, research suggested that aspirin does not reduce the chances of developing most types of cancer, but may reduce the chances of colorectal cancer.

In a study published in JAMA Oncology in 2024, women and men who took daily low-dose aspirin were less likely to develop colorectal cancer in the next 10 years.1  The benefits were greatest for people with the unhealthiest lifestyles, as measured by BMI, smoking, alcohol use, and lack of exercise.

In 2016, the U.S. Preventive Service Task Force (USPSTF), an independent group of medical experts, recommended low-dose aspirin “for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk [risk of developing cardiovascular disease], are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years”.2   They did not recommend aspirin to prevent all types of cancer, only colorectal cancer.

Primary prevention means preventing a disease that a person has not yet developed. As you can see above, there were quite a few caveats on who might benefit from “baby” low dose aspirin (typically 81mg).  For example, patients with an increased risk of bleeding due to certain medications, or with a history of other medical conditions such as stomach or intestinal ulcers, kidney disease, or severe liver disease.2

Recommended Guidelines in 2019 from the American College of Cardiology (ACC) and the American Heart Association were not as enthusiastic about aspirin for primary prevention of heart disease, saying that “low-dose aspirin might be considered” for certain patients.3 They did not comment on aspirin to prevent cancer.

The latest research is quite consistent with earlier studies. Studies published more than a decade ago had mixed results for cancer prevention. One study suggested that a daily dose of at least 75mg aspirin taken for several years could reduce the risk of developing colorectal cancer or dying from it.4 Other studies suggested that aspirin may reduce mortality from other cancers, as well as reducing the chances of cancer spreading.5,6 However, a 2019 meta-analysis that combined results from several studies found aspirin did not significantly affect overall cancer mortality.7  One clinical trial known as ASPREE (Aspirin in Reducing Events in the Elderly) found that individuals who took aspirin were more likely to die from cancer.

In conclusion, more research is needed to conclusively determine whether daily baby aspirin can help to prevent cancer, but the benefits seem conclusive for preventing colorectal cancer, especially for men and women with unhealthy habits.

Bottomline: Do I Need Aspirin?

Some patients think they may as well take aspirin, because it might help and won’t harm.  That’s not an accurate assumption.  Aspirin can have risks even at low doses. You should discuss aspirin therapy with your doctor and let him or her know:

  • Your medical history and the medicines you are currently using, whether they are prescription or over-the-counter
  • Any allergies or sensitivities you may have to aspirin
  • Any vitamins or dietary supplements you are currently taking

Other Ways to Prevent Heart Disease and Cancer

To reduce your risk of colorectal cancer, don’t smoke, don’t drink alcohol in excess, have a healthy diet, stay physically active, and maintain a healthy weight.  Being older, and having a family history of colon cancer, Crohn’s disease, or ulcerative colitis are the risk factors you can’t control.8

To reduce your risk of heart disease, don’t smoke, keep your cholesterol and blood pressure under control, and do what you need to do to prevent diabetes.  Being a man and older are risk factors you can’t control.9

 

All articles on our website have been approved by Dr. Diana Zuckerman and other senior staff.

References:

  1. Sikavi DR, Wang K, Ma W, et al. Aspirin Use and Incidence of Colorectal Cancer According to Lifestyle Risk. JAMA Oncol. 2024;10(10):1354–1361. doi:10.1001/jamaoncol.2024.2503
  2. Final recommendation statement: Aspirin use to prevent cardiovascular disease and colorectal cancer: Preventive Mmedication. U.S. Preventive Services Task Force. 2017. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer
  3. Donna K. Arnett, Roger S. Blumenthal,  Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. Journal of the American College of Cardiology. 2019;17:CIR0000000000000678.   http://www.onlinejacc.org/content/early/2019/03/07/j.jacc.2019.03.010?_ga=2.223365151.502443893.1555427130-1631669420.1554414836
  4. Rothwell PM, Wilson M, Elwin CE, et al.  Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754): 1741-50. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61543-7/fulltext
  5. Rothwell PM, Folkes FG, Belch JF, et al.  Effect of daily aspirin on long-term risk of death due to cancer: Analysis of individual patient data from randomised trials. Lancet. 2011;377(9759): 31-41. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62110-1/fulltext
  6. Rothwell PM, Wilson M, Price JF, et al. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826): 1591-1601.   https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60209-8/fulltext
  7. Zheng SL, Roddick AJ.  Association of aspirin use for primary prevention with cardiovascular events and bleeding events: A systematic review and meta-analysis. JAMA. 2019;321(3):277-287. https://www.ncbi.nlm.nih.gov/pubmed/30667501
  8. Colorectal Cancer Risk Factors. American Cancer Society. https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/risk-factors.html
  9. How to Prevent Heart Disease. Medline Plus.  Last reviewed 2015.   https://medlineplus.gov/howtopreventheartdisease.html

 

Prostate Cancer: Diet and Dietary Supplements

Diet, Habits, & Other Behaviors, Prevention, Prostate Cancer
Brandel France de Bravo, MPH, Caitlin Kennedy, PhD, Anna E. Mazzucco, PhD, and Laura Gottschalk, PhD, Cancer Prevention & Treatment Fund

Prostate cancer is the second most common cancer among American men, and the second leading cause of cancer deaths among them as well. The American Cancer Society estimates almost 192,000 new diagnoses of prostate cancer in 2020, and more than 33,000 prostate cancer related deaths.[1] 

Compared to most cancers, prostate cancer usually progresses very slowly, and many men live with it for years and even decades. Once diagnosed, some men decide to undergo treatment to halt the progression of the disease, and others refrain from treatment, preferring instead to closely monitor the cancer’s progression. Those who choose “active surveillance” do this because the medical and surgical treatments for prostate cancer often cause very undesirable side effects, and because most men with prostate cancer will die from something else. This strategy is especially likely for older men in the earliest stage of the disease.

At one time, it was unheard of to suggest that diet might have a role to play in battling prostate cancer. But there is now evidence that certain foods and dietary supplements have an impact on prostate health—both positive and negative. Some foods or supplements appear to promote prostate health and prevent cancer cells from developing, but others should not necessarily be taken by men who already have prostate cancer.

The role of diet drew researchers’ attention when they noticed that prostate cancer rates vary greatly from one country to another, with the highest rates appearing in countries where people tend to eat a lot of fat. Studies also show that men who are obese or have a high fat diet are more likely to have prostate cancer.[2] Diets high in saturated fats, such as the animal fats found in red meat, may pose the greatest risk. The lowest rates of prostate cancer are found in Asian countries where men eat a lot of soy foods, a rich source of naturally occurring phytoestrogens. It was hoped that by increasing men’s intake of phytoestrogens, they might reduce their risk of prostate cancer, slow its progression, or reduce the risk of prostate cancer recurring, but at least three studies have failed to find any protective benefit from phytoestrogens.[4][5][6]

Dietary Supplements

As more and more people take dietary supplements containing antioxidants, studies have been conducted to determine their effect on reducing the risk and growth of cancers, including prostate cancer. Three antioxidants that have received attention with regard to prostate health are vitamin E, selenium, and vitamin D.

Studies comparing men who live in areas of the country with high levels of selenium to men in areas with low levels suggest that this mineral protects against prostate cancer. Selenium was believed to reduce the risk of developing prostate cancer because it keeps cells from proliferating or dying off in a rapid or unusual way. An analysis in 2002 of the Nutritional Prevention of Cancer Trial revealed that the men who took selenium supplements daily were half as likely to be diagnosed with prostate cancer.[7] However, a 2014 report based on the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicated that selenium supplements increased the risk of prostate cancer by 91% and taking vitamin E supplements increased the risk of prostate cancer by 17%.[8] This result led the researchers to discourage men over 55 from taking amounts of vitamin E higher than the recommended dietary allowance (RDA), which is 15 mg of alpha-tocopherol.  Moreover, a 2009 study found that higher selenium levels in the blood may worsen prostate cancer in many men who already have the disease.[9] As a result of this trial, the researchers have encouraged men over 55 to limit their intake of selenium to the recommended dietary allowance (RDA) of 55 mcgs.

The SELECT findings on selenium don’t mean that antioxidants have no role to play in preventing cancer or slowing its spread. Some antioxidants may be helpful but some may encourage small cancers to grow larger.  A 2014 study by researchers in the U.K. tested the effect of Pomi-T, a supplement that contains broccoli, pomegranate, green tea, and turmeric on the health of men with prostate cancer. After six months, they found that the men taking Pomi-T had a smaller increase in PSA, a protein that becomes elevated with prostate cancer, as compared to men with prostate cancer who didn’t take Pomi-T. The researchers suggest that the unique blend of polyphenols and antioxidants in the supplement had a beneficial effect on health of these prostate cancer patients.[10]

A study published in 2016 brought yet another antioxidant, vitamin D, into the prostate cancer discussion. Vitamin D is well known for its role in helping build strong bones and teeth, but it may also contribute to the fight against cancer (read more here AND here). The prostate cancer study looked at the levels of vitamin D in men who had their prostates removed due to cancer. They found that men who had the most aggressive forms of prostate cancer had lower levels of vitamin D in their blood compared to men with less aggressive forms of cancer.[11] It is not yet known whether higher levels of vitamin D prevent more aggressive forms of prostate cancer or if aggressive prostate cancer lowers levels of vitamin D. Since it is impossible to know if low levels of vitamin D is a cause or effect of aggressive prostate cancer, and since high levels of vitamin D can be dangerous, more research is needed before experts will know if men diagnosed with prostate cancer should try to take more vitamin D.

Bottom Line: We need studies to determine exactly how diet and dietary supplements can be used to prevent prostate cancer and slow its spread. Meanwhile, men should reduce saturated fats as much as possible. While the jury is still out on phytoestrogens, men may benefit from eating more soy products—especially if they are eating them in place of red meat!

For more on cancer and antioxidants, read here.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

  1. American Cancer Society. Key Statistics for Prostate Cancer. Cancer.org. https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Updated 2020.
  2. Narita, S., Nara, T., Sato, H., Koizumi, A., Huang, M., Inoue, T., & Habuchi, T. (2019). Research evidence on high-fat diet-induced prostate cancer development and progression. Journal of clinical medicine, 8(5), 597.
  3. Ma R, Chapman K. A systematic review of the effect of diet in prostate cancer prevention and treatment. Journal of Human Nutrition and Dietetics. Vol (22)2009:187-199.
  4. Ganry O. Phytoestrogens and prostate cancer risk. Preventive Medicine. Vol (41) 2005:1-6.
  5. Ward H, Chapelais G, Kuhnle GC, Luben R, Khaw KT, Bingham S. Lack of Prospective Associations between Plasma and Urinary Phytoestrogens and Risk of Prostate or Colorectal Cancer in the European Prospective into Cancer-Norfolk Study. Cancer Epidemiology Biomarkers & Prevention Vol (17) 2008: 2891-2894.5
  6. Bosland MC, Kato I, Zeleniuch-Jacquotte A, Schmoll J, Rueter EE, Melamed J, Kong MX, Macias V, Kajdacsy-Balla A, Lumey LH, Xie H, Gao W, Walden P, Lepor H, Taneja SS, Randolph C, Schlicht MJ, Meserve-Watanabe H, Deaton RJ, & Davies JA. Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy. JAMA 2013; 310(2): 170-178. doi: 10.1001/jama.2013.7842
  7. Duffield-Lillico AJ, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: A summary report of the Nutritional Prevention of Cancer Trial.Cancer Epidemiology, Biomarkers, and Prevention. Vol (11) 2002: 630-639.
  8. Kristal AR, et al., Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk.  Journal of the National Cancer Institute, 2014.
  9. Chan JM et al. Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate-or High-Risk Prostate Cancer. Journal of Clinical Oncology. Vol (27) 2009: 3577-3583.
  10. Thomas, R., Williams, M., Sharma, H., Chaudry, A., & Bellamy, P. (2014). A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the UK NCRN Pomi-T study. Prostate Cancer and Prostatic Diseases, 17(2), 180-186.
  11. Nyame Ya, et al. Associations between serum vitamin D and adverse pathology in men undergoing radical prostatectomy. J Clin Oncol. 2016 Feb 22.

Do high blood pressure and extra weight make prostate cancer deadly?

Prostate Cancer
By Jessica Cote, BS and Anna Mazzucco, PhD
2014

Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths in men in the United States. One in six men will be diagnosed with prostate cancer in his lifetime, with about 90% of cases occurring in men 55 and older, and 71% of deaths occurring in men 75 and older.1

Even though prostate cancer is a leading cause of death, most prostate cancers are not very dangerous. Two key facts are important to remember:

  1. Many older men who aren’t diagnosed with prostate cancer have the disease but will never be harmed by it.
  2. Because prostate cancer usually grows very slowly, most men who are diagnosed with prostate cancer will die of something other than prostate cancer. A 2012 study showed that only 16% of men in the U.S. diagnosed with prostate cancer died from this disease.2

Although the death rate is relatively low, it is important to find ways to prevent prostate cancer deaths with treatments that do not have serious side effects.

The cause of prostate cancer is unknown, but older men, African-American men, men who drink high amounts of alcohol, farmers, and men who were exposed to Agent Orange pesticides are all at higher risk.3  The high incidence of prostate cancer in Western Europe and North America is thought to be related to a “Western” diet, which is high in refined grains, other processed foods, and saturated fats.4  Meat and dairy products tend to have more saturated fats than other foods, and red meat has more saturated fat than chicken or fish.

Does weight increase the risk?

A 2014 report indicates that being obese can increase a man’s risk of advanced prostate cancer.5  The report was based on meta-analyses that combined and analyzed the results of several large studies. The report analyzed the impact of obesity that was measured three ways, by body mass index (BMI), waist circumference, or waist-hip ratio (WHR), and found a similar link.  This suggests that preventing potentially fatal forms of prostate cancer is another reason to maintain a healthy weight.

What is metabolic syndrome and does it increase the risk of dying from prostate cancer?

Metabolic syndrome refers to a group of factors that increase the risk of coronary artery disease, stroke, and type 2 diabetes.6 The syndrome includes insulin resistance, obesity (especially extra weight around the middle and upper body parts), high blood pressure, and high levels of blood sugar and fats.

Recent research tells us that metabolic syndrome is also related to prostate cancer deaths. A 2012 study of the medical records of more than 289,000 men, published in 2012 in the journal Cancer, found that the risk of getting prostate cancer didn’t seem to be affected by metabolic factors, but the risk of dying from prostate cancer was.7  During a 12-year period, 6,673 men were diagnosed with prostate cancer and 961 died from the disease. Men with a higher BMI, elevated blood pressure, and a high composite metabolic score (from BMI, blood pressure, and blood levels of glucose, cholesterol and triglycerides) were more likely to die from prostate cancer than other men.

The study was well-designed with a large sample size and health information that was collected from patients during many medical exams. However, like most studies, this study wasn’t perfect. Researchers did not record details about the prostate cancer such as tumor stages and patterns of spreading, nor did they consider family history of cancer, medication, socioeconomic status, or other diseases that may have occurred in addition to prostate cancer. All those factors could have influenced the chances of the men dying of prostate cancer. Even so, with hundreds of thousands of men in the study, it is likely that the results should be taken seriously: men can increase their chances of surviving prostate cancer (as well as heart disease) if they reduce metabolic problems.

When we consider this study as well as the 2014 report together, it provides convincing evidence that obesity increases men’s risk of dying of prostate cancer.   While prostate cancer is common among all men, being obese and having the common problems associated with obesity (such as high blood pressure and cholesterol) may make the cancer more aggressive.

What else should men do to lower their risk of getting and dying from prostate cancer?

Cancer screening seems like the best way to reduce the risk of cancer, but that is only true if the screening test is accurate and the treatment is safe and effective.  In 2012, the U.S. Preventive Services Task Force recommended against prostate cancer PSA screening tests for men of any age if they do not present any symptoms of prostate cancer (see: Are Annual Prostate Cancer Screenings Necessary? Should Early Stage Prostate Cancer Be Treated?). The Task Force was convinced that the benefits of PSA-based screening for prostate cancer did not outweigh the harms.8

Even though screening isn’t helpful for men with no symptoms of prostate cancer, it could be very effective at saving the lives of men with symptoms.  If you have one or more symptoms of prostate cancer (trouble urinating, blood in the urine, discomfort in the pelvic area), talk to your doctor about getting a PSA or other test for prostate cancer.

Bottom line: If you’re a man over 50, even if you’ve never been diagnosed with prostate cancer and aren’t presenting any symptoms, the latest research tells us it’s a good idea to do the following:

  1. Eat a diet low in saturated fats. This means limiting intake of high-fat cheeses and other dairy products and choosing leaner cuts of meat.
  2. Watch your intake of sugars and starches– this includes beer, wine and alcohol of all kinds. While 1-2 drinks a day can lower your risk of heart disease and possibly reduce your risk of stroke, more than that can increase your risk of diabetes or related metabolic problems.9
  3. Weigh yourself regularly.  Most men don’t, but if you weigh yourself frequently, it will help you keep your weight down.  If you gain a few pounds, you should eat less and exercise more until your weight is back down.
  4. If you have type 2 diabetes and have been prescribed a special diet or medicine, be sure to stick to it and take your pills as directed.

Pomegranate Juice and Prostate Health

Diet, Habits, & Other Behaviors, Prostate Cancer, Prostate Cancer
Laura Covarrubias, Cancer Prevention and Treatment Fund

Pomegranate juice contains plenty of antioxidants, but does it improve health, as the ads imply? Pom Wonderful, a large company that makes pomegranate juice and other products from pomegranates, would like you to believe that the juice can prevent or treat a number of health problems, including prostate cancer and erectile dysfunction. However, a close look at the science behind these claims shows that drinking pomegranate juice to treat or prevent prostate cancer and erectile dysfunction might not be worth the cost or the calories.

Prostate cancer is the most common cancer among men, other than skin cancer. (For more on skin cancer, read Tanning Beds: Safe Alternative to Sun? and Running and Skin Cancer Prevention.) Since almost everyone knows someone with prostate cancer, and since treatments can cause erectile dysfunction and incontinence, there is a tremendous desire to find a way to prevent the disease.

Even among men who have not had prostate cancer, erectile dysfunction-the inability to have or maintain an erection (called “ED” in advertisements)-is common. Many men suffering from erectile dysfunction want treatments that are less expensive and more natural than Viagra and other prescription medications.

Drinking pomegranate juice has been touted as an easy solution to decreasing the risk of prostate cancer and improving erectile dysfunction, but does it work? Nearly all of the studies are sponsored by Pom Wonderful, which is selling the products that the studies are evaluating. The company reports having spent at least $35 million on the research; unfortunately, studies sponsored by a product’s manufacturer tend to be biased in favor of the products.[1]

A May 2012 ruling by the Federal Trade Commission (FTC) concluded that Pom Wonderful’s promotional materials about the health benefits of their products are misleading and that their claims that pomegranate juice can treat, prevent, or reduce the risk of certain health conditions (including prostate cancer, erectile dysfunction, and heart disease) were deceptive.[2] Because of federal laws against making misleading disease prevention and treatment claims, the court issued a cease-and-desist order to Pom Wonderful. While the ruling prohibits Pom Wonderful from promoting its juice as a treatment for prostate cancer or erectile dysfunction, it doesn’t prevent the company from making broad claims about pomegranate juice such as that it “promotes prostate health.”

What the Science Says about Prostate Cancer and Pomegranate Juice

Only one study has been published in a peer-reviewed medical journal that looks at the effect of drinking pomegranate juice on prostate cancer. This 2006 study, funded by Pom Wonderful, is often used by the company to back its claims that their juice can help fight prostate cancer.[3] Only 46 men treated with either surgery or radiation for prostate cancer participated. All the men had rising prostate-specific antigen (PSA) levels, which is interpreted as a sign that their prostate cancer had come back, and all were given 8 ounces of Pom Wonderful to drink daily for a period of two years. The study found that the men’s rising PSA levels slowed, which can mean that their cancers were no longer growing as fast. To read more about PSA tests, click here.

In most scientific research, some patients receive a new treatment and the others receive either a placebo (sugar pill) or an older treatment. The Pom study was poorly designed because all the men drank the juice, making it impossible to evaluate the impact of the juice. Since PSA levels vary over time, we can’t know if PSA levels dropped because of the juice or would have dropped even without the juice.  In addition, the study only evaluated 46 men, all of whom had been treated for prostate cancer.  This small number of prostate cancer patients is not large enough to draw conclusions about all men, or even all men who have been treated for prostate cancer.

This 2006 study also looked at samples of cancer cells that were taken from other men with prostate cancer-not the same men who drank the pomegranate juice. These cancer cells were then treated with serum – a component of blood – from the men who drank pomegranate juice to see if the cancer cells stopped growing. The study found that cancer cells died when treated with the serum.  That sounds impressive, but there are many reasons why the serum could have caused the cancer cells to die. The researchers called for a future study with a control group (where cancer cells are treated with nothing), but six years later no study like that has been published.

Studies of pomegranate juice on mice and on human cells were more promising, but also not conclusive. One study funded by the U.S. Public Health Service, a government agency, looked at the effect of pomegranate extract – a very concentrated form of pomegranate juice – on prostate cancer cells that were taken from patients but grown outside of the body.[4] They found that the growth of cancer cells treated with the pomegranate extract was slower in comparison to the cancer cells not treated with the extract. In this same study, scientists also looked at the effects of pomegranate extract on the tumor size of mice with prostate cancer. They saw that the growth rate of the tumors in mice treated with the extract was slower in comparison to the growth rate of tumors in the mice that were not treated.

Another laboratory study found that more prostate cancer cells died in the samples treated with pomegranate juice concentrate provided by Pom Wonderful than in samples treated with different types of pomegranate extract.[5] The researchers believe that the many different chemical compounds in pomegranate juice work together to kill cancer cells, and that the pomegranate extract did not have all of these compounds and so did not have as strong of an effect. However, this study does not tell us if drinking pomegranate juice-rather than applying it to cancer cells-can prevent or treat cancer.  Even if there were research indicating a benefit from drinking the juice, how much juice would men have to drink?

Pom has also funded studies on clogged arteries and diabetes, which required people to drink 8 ounces of pomegranate juice every day (these studies were also inconclusive about the effects of pomegranate juice).[6,7] Even if 8 ounces a day was effective at lowering prostate cancer risk or improving health, this is a solution that not everyone could afford.  The cost of the juice, which would not be covered by health insurance, would be about $780 a month.[8] Drinking 8 ounces of Pom Wonderful adds an additional 160 calories per day, which equals 1,120 calories a week and 4,800 calories a month.  Unless the juice replaces an equally caloric drink, this could increase a person’s weight, which in turn increases the risk of prostate cancer and several other types of cancer (Weight and Cancer: The Latest Research).

What other alternatives are there?  Diets high in fiber and low in meat products and saturated fats have been linked to a lower risk of prostate cancer in men, and these diets also have other positive health effects such as reducing the risk of developing diabetes, heart disease, and stroke.[9,10,11] To learn more about the connections between diet and prostate cancer, read here.

What the Science Says about Erectile Dysfunction and Pomegranate Juice

There is even less evidence behind Pom Wonderful’s claims that drinking pomegranate juice decreases erectile dysfunction than there is about prostate cancer or other illnesses. Two studies used by Pom Wonderful to back these claims were conducted on rabbits – not humans.[12,13]These studies found that antioxidants (not pomegranate juice specifically) may be useful against erectile dysfunction, although no definite conclusions were made even for rabbits, and certainly not for humans.

The only study of humans used by Pom Wonderful divided the 53 participants with erectile dysfunction into two groups.[14] One group was assigned to drink pomegranate juice every day for the first 28 days, while the other group drank a placebo drink. After 28 days, the men answered questions about their erectile function. For the next two weeks, both groups stopped drinking their assigned drink (juice or placebo) – this time is known as a “washout” period. Research studies use washout periods to make sure that any effects of the treatment do not continue to be measured when the person begins drinking the new drink. After the washout period, the groups switched drinks so that the group that drank pomegranate juice drank the placebo for 28 days (and vice versa). Again, the men answered the same questions about their erectile function. Overall, the researchers did not find any statistically significant difference between the two groups.  Although there was a slight decrease in erectile dysfunction among the men drinking the pomegranate juice, the difference was small and could have occurred by chance. The researchers called for a larger and longer study to determine if pomegranate juice really does improve erectile dysfunction. We agree.

More Research Needed

Better research on men is needed to determine if regularly drinking pomegranate juice or taking pomegranate extract pills prevents or helps treat prostate cancer, erectile dysfunction, or other conditions. In the meantime, there is no harm in drinking pomegranate juice as long as it does not contribute to overweight or obesity.  Men who choose to drink pomegranate juice should consider the extra calories and cost.

Bottom Line:

  • There is no strong evidence to support the claim that pomegranate juice protects against prostate cancer or helps with erectile dysfunction.
  • Age increases the likelihood of prostate cancer and erectile dysfunction, and weight gain can also increase the chances of getting prostate cancer or having it return after treatment.[15]
  • If you or a loved one is undergoing treatment for prostate cancer, pomegranate juice is not an effective alternative.

References:

  1. Lexchin J, Bero L, Djulbegovic B. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. Bmj. 2003;326(May). Available at: http://www.bmj.com/content/326/7400/1167.short. Accessed June 6, 2012.
  2. United States of America Federal Trade Commission. Initial Decision. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1245105.
  3. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;12(13):4018-26. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16818701. Accessed March 28, 2012.
  4. Malik A, Afaq F, Sarfaraz S, et al. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(41):14813-8. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1253570&tool=pmcentrez&rendertype=abstract.
  5. Seeram NP, Adams LS, Henning SM, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. The Journal of nutritional biochemistry. 2005;16(6):360-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15936648. Accessed May 24, 2012.
  6. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clinical nutrition (Edinburgh, Scotland). 2004;23(3):423-33. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15158307. Accessed May 2, 2012.
  7. Rosenblat M, Hayek T, Aviram M. Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages. Atherosclerosis. 2006;187(2):363-71. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16226266. Accessed May 13, 2012.
  8. United States of America Federal Trade Commission. Initial Decision. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1245105.
  9. Cohen JH, Kristal a R, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. Journal of the National Cancer Institute. 2000;92(1):61-8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10620635.
  10. Ma RW-L, Chapman K. A systematic review of the effect of diet in prostate cancer prevention and treatment. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2009;22(3):187-99; quiz 200-2. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19344379. Accessed June 10, 2012.
  11. Anderson JW, Baird P, Davis RH, et al. Health benefits of dietary fiber. Nutrition reviews. 2009;67(4):188-205. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19335713. Accessed March 3, 2012.
  12. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. The Journal of urology. 2005;174(1):386-93. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15947695. Accessed July 16, 2012.
  13. Zhang Q, Radisavljevic ZM, Siroky MB, Azadzoi KM. Dietary antioxidants improve arteriogenic erectile dysfunction. International journal of andrology. 2011;34(3):225-35. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20584092. Accessed July 16, 2012.
  14. Forest CP, Padma-Nathan H, Liker HR. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study. International journal of impotence research. 2007;19(6):564-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17568759. Accessed July 16, 2012.
  15. Kaluza J, Wolk A, Larsson SC. Red Meat Consumption and Risk of Stroke: A Meta-Analysis of Prospective Studies. Stroke; a journal of cerebral circulation. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22851546. Accessed August 9, 2012.

Physician Groups Make Recommendations to Reduce Healthcare Costs

Breast Cancer, Cervical Cancer & HPV, Other Cancers, Prostate Cancer
Nyedra W. Booker, PharmD, MPH, Cancer Prevention and Treatment Fund
  • Does an 18-year-old girl need a pap smear?
  • Should a patient with a mild sinus infection be given antibiotics?

You might be surprised that the answer to both questions is NO according to leading physicians.

In an effort to improve medical care in the U.S. and save healthcare dollars at the same time, each of nine U.S. medical groups recently proposed a list of Five Things Physicians and Patients Should Question. This is a bold move by medical groups who collectively represent almost 375,000 physicians.  Currently, doctors are paid more for ordering more tests and diagnostic procedures, so these recommendations  are not financially beneficial to the physicians involved, but have the potential for reducing the cost of medical care for patients, health insurance companies, and government health programs such as Medicare, Medicaid, and Veterans healthcare.

The medical groups represent a wide range of medical care.  The nine groups include the American Academy of Allergy, Asthma & Immunology; American Academy of Family Physicians; American College of Cardiology; American College of Physicians; American College of Radiology; American Gastroenterological Association; American Society of Clinical Oncology; American Society of Nephrology and the American Society of Nuclear Cardiology.

Recommendations

Here are just a few of the groups’ recommendations:

Hives – Routine diagnostic testing (such as immunoglobulin E (IgE), a skin prick or blood test for allergies) is not recommended for patients with chronic hives, because such testing is usually ineffective at identifying the cause. [American Academy of Allergy, Asthma & Immunology]

Pap Smears – Routine pap smears to screen for cervical cancer are not recommended for women under the age of 21. [American Academy of Family Physicians]

Cardiac Stress Test – Cardiac stress test imaging (a procedure where dye is inserted into the blood stream and images show how well the blood is flowing through the heart) is not recommended for cardiac patients at their annual check-ups unless symptoms are present. [American College of Cardiology]

X-Rays and MRIs for Back Pain – Imaging (X-rays, MRIs) is not recommended for a patient with lower back pain unless a specific cause has been identified. [American College of Physicians]

MRIs and CCTs of the Brain – Imaging of the brain, including MRIs and CCTs (cranial computed tomography), is not recommended for a patient with a headache unless specific risk factors have been identified. [American College of Radiology]

Colorectal Cancer Screening– Colorectal cancer screening by any method (including flexible sigmoidoscopy, computed tomography colonography, double-contrast barium enema test) should be repeated every 10 years in low to average-risk patients who received a normal result at their last colonoscopy screening.  This is less frequently than previous recommendations.  It is recommended that people get their first colonoscopy at age 50. [American Gastroenterological Association]

Breast Cancer Testing – Imaging (PET, CT and radionuclide bone scans) is not recommended for patients with early-stage breast cancer at low risk for metastasis (cancer spreading to other parts of the body). [American Society of Clinical Oncology]

Cancer Screening – Routine cancer screenings (including colonoscopy, mammography and pap smears) are not recommended for patients on dialysis who have a short life expectancy, unless specific signs and symptoms are present. [American Society of Nephrology]

Chest Pains – Routine cardiac imaging including a stress echocardiogram (which  uses ultrasound to show how well the heart is pumping blood) is not recommended for a patient with chest pains who is at low risk for a heart attack or cardiac-related death, is able to exercise, and has a normal electrocardiogram (EKG).[American Society of Nuclear Cardiology][1]

A complete list of all 45 recommendations is available at: http://choosingwisely.org

How Will This Help?

Healthcare spending in the United States reached almost $2.6 trillion in 2010 and is expected to rise to around $4.6 trillion by 2020 unless major changes are made to eliminate unnecessary procedures, according to the Centers for Medicare & Medicaid Services.[2] An increase in the number of people living with chronic illnesses, rising prescription drug prices, and the high administrative costs of managing healthcare programs will contribute to increasing costs. While many continue to debate the exact reasons why healthcare spending is out of control, most agree that something needs to be done immediately.

In 2011, the American Board of Internal Medicine Foundation (ABIM) announced the Choosing Wisely campaign, and the National Physicians Alliance helped develop a multi-year initiative that would promote discussion among physicians, patients and consumer groups, aimed at decreasing healthcare costs by reducing unnecessary tests and procedures. Each participating group of physicians was asked to develop a list of five recommendations based on evidence from research findings. These recommendations were specific to their respective medical fields.

While many doctors and health experts understand that more medical care, and more expensive medical care, is not necessarily better medical care, studies show that the American public is wary of health care guidelines, even when they’re based on strong evidence. Patients and consumers tend to assume that running more tests and relying on newer, more costly technologies translate into health improvements (see Is Newer and More Expensive Care Better?).  As for doctors, the need to pay for expensive new imaging devices by charging for their use, the desire to give patients a clear diagnosis, and concerns about harming a patient by missing a diagnosis can all contribute to ordering unnecessary imaging and other tests.

Given this divide, it’s not surprising that Choosing Wisely has generated praise and concern. While many are praising the initiative as a step in the right direction to reduce the staggering cost of healthcare in the U.S., others question whether these cost-cutting strategies will come at the expense of good patient care.

Next Steps

The American Board of Internal Medicine Foundation and the National Physicians Alliance will continue to work with the nine medical specialty groups and several partnering organizations, including Consumer Reports and the American Association of Retired Persons (AARP), to develop tools and resources to help physicians discuss healthcare decisions with their patients. There will also be at least eight additional medical specialty groups joining the initiative and releasing their recommendations in the fall of 2012.

References:

  1. Choosing Wisely: An Initiative of the ABIM Foundation. Accessed April 04, 2012. http://choosingwisely.org/?page_id=13.
  2. Centers for Medicare & Medicaid Services. “National Health Expenditure Projections 2010-2020.” Accessed April 09, 2012. https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/Downloads/proj2010.pdf

 

Can Sleeping Pills Cause Cancer?

Colon Cancer, Diet, Habits, & Other Behaviors, Lung Cancer, Medical Treatments with Cancer Risks, Other Cancers, Prostate Cancer
Brandel France de Bravo, MPH, Kousha Mohseni, MS, Cancer Prevention and Treatment Fund

When we hear “sleeping pills,” most of us think of prescription drugs such as Ambien (generic name zolpidem), Restoril (temazepam), and Lunesta (eszopiclone).  While prescription sleep medications are big business — more than $41 billion/year in the U.S. many people with trouble sleeping turn to over-the-counter antihistamines such as Tylenol PM and Benadryl.[1]  However, the use of these drugs may take a nosedive in light of the findings of a study published in the prestigious British Medical Journal. Led by researchers at the Scripps Clinic Viterbi Family Sleep Center in California, the study shows that people who take these drugs are significantly more likely to be diagnosed with cancer or to die within the next two and a half years than people who don’t take them. Author Dr. Daniel Kripke estimates that these popular sleep medications could cause 320,000 to 507,000 deaths in just one year.

The researchers looked at 10,529 primary care patients who were prescribed sleeping pills between 2002 and 2007 and compared the health of each of them to at least two very similar patients without such prescriptions who were the same sex, ethnicity, marital status, smoking status, and had similar health conditions, alcohol use and BMI (which measures if a person is overweight). The patients were followed for 2.5 years on average, and were from a Pennsylvania clinic that serves a mainly low-income population.

Sleeping Pills, Death, and Cancer

Patients who were prescribed sleeping pills were at least three to five times more likely to have died during the study than were the patients not prescribed sleeping pills. Even the patients who were prescribed fewer than 18 pills per year were at higher risk of dying: 3.6 times higher. Patients who were prescribed more than 132 pills a year were more than five times as likely to die.

The researchers were careful to exclude from the study patients who were diagnosed with cancer before the study or very early in the study. Heavy users of sleeping pills (over 132 pills prescribed per year) had a 35% greater risk than those with fewer pills prescribed.  Among those with prescriptions for sleeping pills, the increased risk of their developing lymphoma, lung cancer, colon and prostate cancer was greater than the risk from being a current smoker.

Before this study, there were at least 18 other studies showing an increased risk of death for people taking sleeping pills, and several also showed an increased risk of cancer.  However, this study is especially well-designed and the only one that includes the newer, short-acting class of popular sleeping pills known as nonbenzodiazepines. These were generally believed to be safer than previous generations of sleeping pills because they wear off more quickly. In fact, before this study it was believed that the worst side effect was weight gain due to night time raids on the refrigerator while sleep walking.

Among study participants, the most commonly prescribed sleeping pill was zolpidem (sold as Ambien, Edluar, or Zolpimist), followed by temazepam (a benzodiazepine sold as Restoril). However, prescriptions for the use of any sleep aid was associated with a significant increase in the risk of death, including eszopiclone (”Lunesta”), zaleplon (”Sonata”), barbiturates, as well as antihistamines such as diphenhydramine (the active ingredient in Benadryl), which is also used in many over-the-counter sleep aids. The average age of patients was 54, but the study found harm associated with sleeping pill use in every age group.[2]

All the sleeping pills showed a similar increased risk of death except Lunesta, which showed a more than 500% increased risk compared to any of the other sleeping pills.  However, Lunesta was a relatively new drug at the time of the study, and relatively few people took it. For that reason, it is not possible to say whether the risk of Lunesta is really that high.  Also important to note: This study did not evaluate cancer among patients taking Belsomra, a newer sleeping aid with numerous side effects.[3]

One shortcoming of the study is that getting a prescription for a sleeping pill is not the same as taking sleeping pills.  It is possible that some of the people with prescriptions, especially for small numbers of pills, never took any of them. It is also possible that people who did not have prescriptions for sleeping pills took Benadryl or other over-the-counter antihistamines to help them fall asleep, instead of the prescription version of the same pills.  However, those shortcomings would tend to underestimate the risk of sleeping pills, rather than overestimate the risks.

In addition to the major study cited above, there is other evidence linking sleeping pills to cancer.  For example, a study of Taiwanese patients published in 2012 found that Ambien promoted viral infections, which reflects a weakening of a person’s ability to fight off infections and diseases.[4]  That could explain the increased risk of cancer.

Also, a study published in the Korean Journal of Family Medicine in 2018 found that sleeping pills were strongly associated with esophageal, kidney, prostate, liver, stomach and pancreatic cancers. Of all the sleeping pills in the study, Ambien most strongly predicted a diagnosis of cancer.[5]

But Why?

What could possibly explain these increased risks?  Are people who are prescribed sleeping pills more anxious or stressed out? There is evidence that they are more likely to have car accidents or to fall down, probably because of the residual effects of the drugs during the day.  Other studies show an increase in infections among people taking sleeping pills, and that can also increase the risk of cancer and death from other causes. These other studies all suggest that sleeping pills really do increase the risk of dying and there are no logical explanations to explain away the substantial increased risks found in this study, especially the increased risk of cancer.

While the researchers can’t say for sure that the sleeping pills caused death or cancer, many people who used to take these medications should think about these new research findings and consider other, safer ways to fall asleep.  The sleep specialists who conducted the research suggest that since these sleeping pills have limited benefits, old-fashioned sleep aids like warm milk, as well as cognitive-behavioral approaches that can be taught and used for the rest of your life, would be excellent alternatives.  If you decide to toss your sleeping pills, be sure to see our article Drugs in the Drinking Water for tips on safe medicine disposal.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References:

  1. Consumer Reports. Why Americans Can’t Sleep. ConsumerReports.org. https://www.consumerreports.org/sleep/why-americans-cant-sleep. Updated January 14, 2016. Accessed October 15, 2018.
  2. Kripke DF, Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: a matched cohort study. British Medical Journal. Open 2012;2:e000850 doi:10.1136/bmjopen-2012-000850
  3. Kripke, D. F. (2015). Is suvorexant a better choice than alternative hypnotics? F1000Research, 4, 456. http://doi.org/10.12688/f1000research.6845.1
  4. Kao, C.-H., Sun, L.-M., Liang, J.-A., Chang, S.-N., Sung, F.-C., & Muo, C.-H. (2012). Relationship of Zolpidem and Cancer Risk: A Taiwanese Population-Based Cohort Study. Mayo Clinic Proceedings, 87(5), 430–436. http://doi.org/10.1016/j.mayocp.2012.02.012
  5. Kim, D.-H., Kim, H.-B., Kim, Y.-H., & Kim, J.-Y. (2018). Use of Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies. Korean Journal of Family Medicine, 39(4), 211–218. http://doi.org/10.4082/kjfm.17.0025