Prostate Ca: Are more men presenting with metastatic disease?

A new study reports a recent 72% increase in the number of men initially presenting with metastatic prostate cancer in a select cohort of U.S. hospitals.

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Since its publication online in Prostate Cancer and Prostatic Diseases (July 19, 2016), the study has been the source of controversy over its findings and how they have been reported.

The authors utilized the National Cancer Data Base, an oncology data set from more than 1,400 contributing centers that captures approximately 70% of all incident cancers in the U.S. They report that 2.45% of prostate cancer was metastatic at presentation in 2004, and this percentage increased to 4.31% of cases in 2013.

“Overall, this represents a very small percentage of men who present with prostate cancer, but this relative change is notable,” said senior author Edward M. Schaeffer, MD, of Northwestern University Feinberg School of Medicine, Chicago.

Dr. Schaeffer and colleagues analyzed 767,550 men who presented with prostate cancer from 2004 to 2013. The authors’ overall goal was to evaluate the landscape of men presenting with prostate cancer over a decade.

According to Dr. Schaeffer, they sought initially to determine whether a temporal relationship existed between relaxation in screening practices and increases in advanced or metastatic prostate cancer. However, the authors ultimately concluded: “These findings cannot be explained completely by reactions to the [U.S. Preventive Services Task Force] recommendations alone, as increases in metastatic prostate cancer began in the years before its release.”

Next: Controversy, media attention

The findings and the way they were reported led to a flood of controversy and media attention after the study’s release. It started with a Northwestern press release about the research, which described rates of metastatic prostate cancer “skyrocketing.” The American Cancer Society subsequently issued a blog post that was critical of the study.

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“This study makes a dramatic claim about an issue all of us have been watching eagerly: namely, whether less PSA screening might lead to more advanced cancers,” Otis M. Brawley, MD, the American Cancer Society’s chief medical officer, said in the blog post. “But the current analysis is far from adequate to answer that question sufficiently.”

But the authors didn’t make that claim, according to Dr. Schaeffer. He suggested that the use of the word “skyrocket” in the news release headline to describe metastatic cancer rates was a poor choice, but the study itself and even the press release go on to explain the findings accurately and in detail, he said.

Among the study’s findings: The annual overall incidence of all prostate cancer did not significantly change from 2004 to 2013. And most men (97%) present with localized prostate cancer at their initial diagnosis. Low-risk prostate cancer incidence fell from 25,708 cases in 2004 to 16,223 in 2013-a 37% decline, which began in 2007. Cases of intermediate-risk prostate cancer went up by 10% from 2004 to 2008 but did not change significantly change in the years to follow. Intermediate-risk prostate cancer incidence was 23% higher in 2013 compared with 2004. High-risk prostate cancer incidence increased from 2004 to 2008, but declined (though not significantly) after that.

But all that isn’t new information, according to Dr. Schaeffer. What is notable and perhaps new, he said, are the findings about metastatic disease.

Metastatic prostate cancer increased 7.1% annually from 2007 to 2013, and its incidence increased in all age groups. The annual incidence of metastatic disease increased from 2007 to 2013 (annual percentage change, 7.1%), and in 2013 was 72% greater than that of 2004. The largest increase among those with the most advanced prostate cancer diagnosis, however, was among men ages 55 to 69 years-the very age group thought to benefit most from early detection and treatment. Those men saw a 92% increase in metastatic prostate cancer from 2004 to 2013.

To frame these changes, the authors also explored median PSA levels among men diagnosed with localized and advanced disease. In men with non-metastatic cancer, median PSA levels were stable during the study period, hovering between 6.1 ng/mL⁻¹ to 6.2 ng ml⁻¹. However, median PSA levels among men with metastatic prostate cancer rose from 25.5 ng/mL⁻¹ at the study’s start to 49.7 ng/mL⁻¹ in 2013, according to the authors.

Possible explanations, according to Dr. Schaeffer, include: an aging population, changes in the population of patients at National Cancer Data Base hospitals, improved imaging leading to increased detection of metastatic disease, shifts in lifestyles (obesity, smoking) affecting cancer development, changes in insurance coverage or access to care, and the disease itself changing and becoming more aggressive.

“One would propose if it were simply that the population was aging, then one would speculate that the mean PSA of men who present with metastatic disease would not change between 2004 and 2013. When we looked at this, the mean PSA between men in 2004 when they presented with metastatic disease was 25 ng/mL⁻¹ and the mean PSA for the men who presented with metastatic disease in 2013 was just under 50 ng/mL⁻¹. So, in my mind, the aging explanation does not completely account for these findings,” Dr. Schaeffer said.

“If more men with cancer were undergoing better metastatic cancer workups, then one would expect to find that men with metastatic disease in 2013 would likely have lower or the same PSA results as those men in 2004. We did not see this, and so this also does not appear to be a leading hypothesis.”

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The authors considered changes in screening behaviors as yet another possibility, he says.

“However, we do not think this is the case, because the major guideline recommendations occurred first in 2008 and in 2012. The effects that we saw occurred before those 2 years,” Dr. Schaeffer said.

Next: Dr. Thrasher - “I personally believe that the study brings to light a possible concerning trend"

“I personally believe that the study brings to light a possible concerning trend,” said Urology Times Editorial Consultant J. Brantley Thrasher, MD.

“It will take more time and more studies to answer the question. I don’t think this study proves the point but it does bring up an interesting question that we will need to follow,” said Dr. Thrasher, who was not involved with the study.

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The article is stimulating a discussion and brings focus to important issues related to appropriate execution of epidemiologic studies, as well as concerns regarding PSA screening and subsequent metastatic disease, according to Christopher Paul Filson, MD, MS, of Emory University School of Medicine, Atlanta, who was not involved with the study.

Dr. Filson said the new study is well-intentioned and demonstrates an increase in the raw number of metastatic prostate cancer cases diagnosed at a select group of hospitals.

“However, these findings cannot be generalized to the population at large in the United States because of the nature of the data used and how the statistical analysis was performed. We don’t know if the changes were related to other trends in patients using data from these hospitals, because we cannot evaluate the total number of patients at risk. However, assessing trends in metastatic prostate cancer after changes in PSA screening policy were enacted is an important topic, because I believe we will see these trends nationally starting in 2012-2013,” Dr. Filson told Urology Times.

The controversy, which was highlighted in a recent New York Times article, emphasized the issues surrounding the dissemination of results of scientific studies, both from institution-based media relations departments and the media outlets themselves, Dr. Filson said.

“The paper went through the appropriate peer-review process, but there should have been a more tempered response by the media,” Dr. Filson said.

Dr. Schaeffer said that he believes the findings will be validated by future studies.

“This work, at the present time, is hypothesis-generating and should be used as an impetus for further exploration,” he said. “Although the piece has been somewhat sensationalized by the media, we are glad that there has been so much intelligent discourse and attention on this important disease.”

More on Prostate Cancer:

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Landmark prostate cancer screening trial criticized

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