Metastatic prostate cancer cases skyrocket: More lax screening rather than more aggressive disease?

Date: July 19, 2016

Source: Northwestern University

Summary: The number of new cases of metastatic prostate cancer climbed 72 percent in the past decade from 2004 to 2013, reports a new study. The report considers whether a recent trend of fewer men being screened may be contributing to the rise, or whether the disease has become more aggressive -- or both. The highest increase is among men ages 55 to 69, who could benefit the most from screening and early treatment. The largest increase in new cases of metastatic prostate cancer was among men 55 to 69 years old, which rose 92 percent in the past decade. Credit: © greenapple78 / Fotolia The number of new cases of metastatic prostate cancer climbed 72 percent in the past decade from 2004 to 2013, reports a new Northwestern Medicine study. The report considers whether a recent trend of fewer men being screened may be contributing to the rise, or whether the disease has become more aggressive -- or both. The largest increase in new cases was among men 55 to 69 years old, which rose 92 percent in the past decade. This rise is particularly troubling, the authors said, because men in this age group are believed to benefit most from prostate cancer screening and early treatment. In addition, the average PSA (prostate-specific antigen) of men who were diagnosed with metastatic prostate cancer in 2013 was 49, nearly double that for men diagnosed in 2004 with an average PSA of 25, indicating a greater extent of disease at diagnosis. The blood level of PSA, a protein produced by cells of the prostate gland, is often elevated in men with prostate cancer. "One hypothesis is the disease has become more aggressive, regardless of the change in screening," said senior study author Dr. Edward Schaeffer, chair of urology at Northwestern University Feinberg School of Medicine and Northwestern Medicine. "The other idea is since screening guidelines have become more lax, when men do get diagnosed, it's at a more advanced stage of disease. Probably both are true. We don't know for sure but this is the focus of our current work." Schaeffer also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The paper will be published July 19 in Prostate Cancer and Prostatic Diseases, a journal from Nature. Schaeffer's research team analyzed information from the National Cancer Data Base. It included 767,550 men from 1,089 facilities nationwide who had been diagnosed with prostate cancer between 2004 and 2013. Over the past decade, there has been a substantial reduction in the number of men being screened for prostate cancer and an associated decline in the overall number of new cases of prostate cancer being reported. "The fact that men in 2013 who presented with metastatic disease had much higher PSAs than similar men in 2004 hints that more aggressive disease is on the rise," Schaeffer said. "If I were a patient, I would want to be vigilant. I firmly believe that PSA screening and rectal exams save lives." If a patient is diagnosed with localized prostate cancer that is aggressive, treatment can be curative. If men present with metastatic prostate cancer, treatments are not curative and only slow disease progression. Most patients with metastatic prostate cancer eventually die from the disease. "There could be a significant increase in prostate cancer death rates if more people are diagnosed with metastatic disease, because treatments can only slow progression, it's not curable," Schaeffer said. The study measured the total number of cases of metastatic prostate cancer, not the incidence, for example, of cases per 100,000. In addition, metastatic disease began rising in 2008, before the change in screening recommendations from the U.S. Preventive Services Task Force. Thus, investigators said, they can't definitively link the increased cases to reduced screening alone. Three percent of those included in the study had metastases, which means prostate cancer cells had spread to other parts of their bodies by the time the cancer was diagnosed. The number of cases of metastatic prostate cancer in 2013 (2,890) was 72 percent greater than that in 2004 (1,685). In middle-aged men 55 to 69 years old, the number rose 92 percent from 702 new cases in 2004 to 1,345 in 2013. "The results indicate that screening guidelines and treatment need to be refined based on individual patient risk factors and genetics," said lead author Dr. Adam Weiner, a Feinberg urology resident. "This may help prevent the growing occurrence of metastatic prostate cancer and potential deaths associated with the disease. This also can help minimize overdiagnosing and overtreating men with low-risk prostate cancer who do not need treatment." "This will be particularly critical for population health economics in the U.S., considering the added cost of care for metastatic prostate cancer and an aging constituency whose population over the age of 65 will double to over a projected 80 million by the year 2050," Schaeffer noted

November 2014

PROVENGE (sipuleucel-T) was FDA approved in 2010 for prostate cancer patients who were hormone refractory (castrate resistant), metastatic, and had little or no pain (symptoms). But because PROVENGE is an immunotherapy, it is different in many ways. It is different in the way it is administered (apheresis & a 1 month schedule). It is different in the way it addresses prostate cancer (kick-starting the immune system, not attacking the cancer cells), and different in the way we measure response (immediate PSA response not expected). So, it remains confusing for some people, but experts weigh in below…..

What the Experts are Saying: 

Dr. Charles (Snuffy) Myers, Prostate Forum - "I am tantalized by the fact that pretreatment with PROVENGE might make subsequent therapies far more effective by bringing in the immune system in a more effective way..."

Dr. Charles Drake, Johns Hopkins Cancer Center - "...It turns out that if the PSA is low when you start, the magnitude of benefit seems to be larger. Whereas if you start with a high PSA (the highest quartile was greater than [approximately] 130 ng/mL), then you have less of a benefit..."

Dr. David Crawford, University of Colorado, Denver - "...people that benefit even more - people with PSA's of less than 2 - number of bone scan lesions less - these people have a very extended survival rate when you use this. It's not just the 4 months, but 18 months..."

Dr. Leonard Gomella, Jefferson Kimmel Cancer Center - on PROVENGE survival benefit - "From my viewpoint, actually the benefit of sipuleucel-T has actually been understated because many of the patients who received the frozen product were on the control [placebo] arm, actually enjoyed a longer survival, decreasing the difference between the control [placebo] arm and the treatment [sipuleucel-T] arm."

In addition, and especially noteworthy: Although African American men only made up about 6% of the men in the phase 3 PROVENGE trial, their survival statistics were measured separately after PROVENGE was FDA approved. Instead of a 4.1 median overall survival benefit, the small group of African American men showed a surprising survival benefit of 30.7 months. There were only 33 men in the African American group, so it is impossible to draw valid scientific proof, but it is certainly noteworthy.
Urology Times May 2012

 Copyright © 2014 Prostate Cancer Research Institute

Omega 3 Fish Oils Linked To Increased Prostate Cancer Risk

Eating a lot of oily fish or consuming omega supplements may not be good for a man's health. New research reveals that males with high blood concentrations of omega-3 fatty acids are at a higher risk of developing prostate cancer.

The finding comes from a large prospective study published in the Journal of the National Cancer Institute.

A 71 percent increased risk of high-grade prostate cancer and a 43 percent increase for all prostate cancers were associated with high concentrations of EPA, DHA, and DPA.

These results are consistent with a 2011 study carried out by the same research team which found that high concentrations of DHA more than doubled the risk of high-grade prostate cancer.

The researchers were shocked to find that higher blood levels of omega-3 fatty acids, usually promoted as good for the heart, were associated with a higher risk of aggressive prostate cancer.

The consistency of these findings could mean that "these fatty acids are involved in prostate tumorigenesis and recommendations to increase long-chain omega-3 fatty acid intake, in particular through supplementation, should consider its potential risks."

The paper's senior author and member of the Fred Hutch Public Health Sciences Division, Alan Kristal, Dr.P.H, said: "we've shown once again that use of nutritional supplements may be harmful."

Theodore Brasky, Ph.D., a research assistant professor at The Ohio State University Comprehensive Cancer Cente, added, "What's important is that we have been able to replicate our findings from 2011 and we have confirmed that marine omega-3 fatty acids play a role in prostate cancer occurrence. It's important to note, however, that these results do not address the question of whether omega-3's play a detrimental role in prostate cancer prognosis."

Dr. Iain Frame, director of research at Prostate Cancer UK, says men reading about the results of this research should not panic about their omega-3 intake. Dr. Frame says: "Omega 3, such as is found in oily fish, has been the focus of a large amount of research in recent years, the majority of which points to it having wide-ranging health benefits when eaten as part of a balanced diet..."

"Much larger and more complex studies will need to take place before we will fully understand how the risks of a diet high in Omega 3 balance against those benefits."

Dr. Frame adds: "Therefore, we would not encourage any man to change their diet as a result of this study, but to speak to their doctor if they have any concerns about prostate cancer."  

Dr. Kristal's study compared the blood level concentrations of omega-3 fatty acids in 834 men who had been diagnosed with prostate cancer with samples from 1,393 men from the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

The lowest risk group for developing prostate cancer had a 3.2 percent blood level concentration of omega-3 fatty acids, compared to 5.7 percent in the high risk group.

The results may come as a surprise to some, considering the number of positive health benefits that are associated with omega-3 fatty acids.

It remains uncertain why high concentrations of these fatty acids are associated with a heightened risk of prostate cancer.

Researchers say it is possible that omega-3 fatty acids are harmful because of they convert into compounds that can damage cells and DNA.

In conclusion, the finding suggests that high levels of omega-3 fatty acids can increase a man's risk of developing prostate cancer.

Guys who drank six cups a day had least risk, says study that debunks long-ago findings Swilling coffee may protect men against Prostate Cancer

By Robert Bazell Chief science and health correspondent

NBC News NBC News

Coffee is good for men, according to research released Tuesday from the Harvard School of Public Health. Those who drank the most coffee regular or decaffeinated have the least risk for prostate cancer, especially the deadliest forms of the disease, the 12-year study of almost 48,000 male health professionals found.

But, wait! Almost exactly 30 years ago this same lab in a separate study concluded that in men and women coffee increased the risk of pancreatic cancer, which is almost always deadly. That study got widespread publicity, but not long afterward the researchers said: "Oops, we made a mistake." Coffee, they said, has no effect on the risk of pancreatic cancer.

That flip-flop from such a prestigious institution contributed greatly to the public distrust of the science of epidemiology and the widespread perception that “one day they say something is good for us and the next day they say it is bad.”

Today's news seems pretty clear. Men who drank the most coffee, six cups or more daily, had a 60 percent lower risk of developing lethal prostate cancer and 20 percent lower risk of developing any form of the disease, according to the study published in the online edition of the Journal of the National Cancer Institute.

Even lighter consumption up to three cups daily was associated with a 30 percent lower risk of lethal prostate cancer.

Because the results were the same whether the coffee was regular or decaffeinated, it's not the jolt of the java that provided the protection, researchers said. Instead, the benefit is likely linked to other compounds in coffee that act as antioxidants, reduce inflammation and regulate insulin.

The new research studied nearly 50,000 U.S. men who reported their coffee consumption every four years from 1986 to 2008. It backs up previous studies that found coffee consumption was associated with lower risk of a wide range of diseases including Parkinson's, type 2 diabetes and liver cancer. Taken together, they support the notion that a wicked coffee habit actually may be good for your health.

Complex and changing So, what happened in the last three decades? For one thing, the science of epidemiology the study of health-related events or disease, including public health research has matured a lot since then and researchers have learned not to make too much of findings that may be later disproved.

It is never easy to study human beings who live in a complex, ever-changing environment. Humans are not lab rats where everything can be controlled. Still, even with the limitations, some kinds of epidemiological studies provide far better evidence than others.

According to Dr. Meir Stampfer, now the chief of epidemiology at Harvard School of Public Health and a co-author of today’s coffee paper "the main difference between (the new study) and the discredited pancreas finding is that ours is prospective, so there is no issue with recall bias."

What does that mean? The first pancreas cancer trial was what is called a “case control trial.” The scientists questioned 369 patients with pancreatic cancer and asked them about their dietary and other habits. Then they asked 644 healthy people the same question. The use of coffee jumped out so much that the authors came to the frightening conclusion that coffee use might account for a substantial proportion of the cases of this disease in the United States.

It sounds scary, but “recall bias” can affect the outcome of a study. People with a terrible disease like pancreatic cancer often wonder why they got it, even though there can be no answer. If they learn that the scientists are interested in coffee as a possibility, they are far more to remember every cup they ever drank than the normal controls. That's where the bias occurs.

The current research is called a prospective trial, which follows participants over a period of time. For the course of the trial, the volunteers have been filling out forms about their dietary and other habits, including tracking their coffee consumption. So when scientists look at the new results, they can be far more confident and may get some cancer fighting benefit.

Of course there's interest in the connection. Prostate cancer is the most frequently diagnosed form of cancer and the second leading cause of cancer death among U.S. men, affecting one in six men during their lifetime. More than 2 million men in the U.S. and 16 million men worldwide are prostate cancer survivors.








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