INCREASE OF METASTATIC PROSTATE CANCER

Last week, major news outlets such as CBS, Newsweek, and Chicago Tribune reported what many US urologists have feared and anticipated: that a study showed metastatic prostate cancer was on the rise in the United States. Some of the media coverage also indicated that controversial recommendations, which have led to less prostate-specific antigen (PSA) testing, were to blame, at least in part.

The study did not prove either point, said critics, including, most prominently, Otis Brawley, MD, chief medical officer of the American Cancer Society, who dissected both the study and the popular interpretation of its results.

Dr Brawley, quoted in an article in the Philadelphia Inquirer, said "it is very possible" that less early detection will result in a higher rate of advanced disease. Nevertheless, "They simply did not prove it," he also said about the new study.

The source of the controversy was an analysis published July 19 in Prostate Cancer and Prostatic Diseases.

In the study, researchers from Northwestern University and the University of Chicago, Illinois, identified all newly diagnosed cases of prostate cancer from 2004 to 2013 in the National Cancer Data Base (NCDB) at 1089 different healthcare facilities in the United States.

They reported that the annual number newly diagnosed cases of metastatic prostate cancer increased in the latter years of study period, from 2007 to 2013 (with an annual percentage change of 7.1%, P < .05).

Also, they highlighted the fact that the annual number of newly diagnosed cases was 72% higher in 2013 (n = 2890) than in 2004 (n = 1685). A Northwestern University press release described this rise as a "skyrocket."

Additionally, the investigators found that the median PSA of men who were diagnosed with metastatic prostate cancer increased from 25.5 ng/mL in 2004 to 49.7 ng/mL in 2013, which is an indicator of a greater extent of disease at diagnosis, according to the press statement.

In their study's discussion section, the authors state that the "social and biologic factors underlying these PSA escapes and rising metastatic prostate cancer cases are unknown."

But a rise in aggressive cancers has been predicted by many experts to be an eventual outcome of US Preventive Services Task Force (USPSTF) guidance from both 2008 (recommending against routine PSA screening in men older than 75 years) and 2012 (recommending against routine PSA use in all healthy men).

In a press statement, senior study author Edward Schaeffer, MD, chair of urology at Northwestern University Feinberg School of Medicine, said, "One hypothesis is the disease has become more aggressive, regardless of the change in screening. 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."

In the study, the authors conclude: "It is likely that trends in the National Cancer Data Base reflect national patterns."

said that the study design does not allow anyone to conclude that the rate of metastatic prostate cancer is increasing in the US population.

"The way epidemiologists measure things like incidence and mortality is to study rates, the number of cases per a number of people (usually per 100,000) to look for trends. But this study, done by a group of urologists, didn't do that. Rather than measure rates of metastatic disease, they looked at the number of cases. That is far from the same thing," he wrote.

The researchers acknowledged this problem to some degree. "Limitations to the current study include the lack of national annual incidence rates in the NCDB," they write. However, they do not explain the significance of that missing data or discuss the crucial difference between incidence (ie, the number of cases) and incidence rates.

The increased number of cases could have various explanations, further commented Dr Brawley.

"Epidemiologists learned long ago that you can't simply look at raw numbers. A rising number of cases can be due simply to a growing and aging population, among other factors," he said.

Another expert expressed similar doubts about the study in an article in the New York Times titled "Flawed Study of Advanced Prostate Cancer Spreads False Alarm." Christopher Filson, MD, an assistant professor of urology at Emory University School of Medicine, Atlanta, Georgia, said, "I don't want to claim their results are wrong. They may be true, but the way they looked at the question brings in too many possible alternative explanations."

To their credit, the researchers did not lay full blame for the increased number of metastatic prostate cancer cases on the USPSTF guidance.

"These findings cannot be explained completely by reactions to the USPSTF recommendations alone, as increases in metastatic prostate cancer began in the years before its release," the authors cautioned.

But media accounts and some related commentary from urologists not involved in the study suggested that the USPSTF recommendations were at fault.

For example, in the above-mentioned Philadelphia Inquirer article, Eric Horwitz, MD, chair of radiation oncology at the Fox Chase Cancer Center in Philadelphia, Pennsylvania, was paraphrased as saying "the new study gives credence to anecdotal reports of spikes in metastatic cases — and to fears that the shift away from screening has gone too far."

In their paper, Dr Schaeffer and colleagues speculated that other factors could explain the increase in the number of cases. "Changes in aggregate screening before the USPSTF grade D recommendation, alterations in the biological aggressiveness of prostate cancer or increases in the ascertainment of metastatic disease (through increased sensitivity and utilization of imaging) are plausible explanations," they write.

In that regard, the authors encouraged restraint about interpreting the results.

But the press statement from Northwestern may have incited dramatic media headlines, suggested Dr Brawley.

He also said that a lot is at stake with this subject, and care must be taken by investigators, public relations departments, and the media.

"The issue of whether and how screening may affect deaths from prostate cancer in the U.S. is an incredibly important one. This study and its promotion get us no closer to the answer, and in fact cloud the waters. We hope reporters understand that and use this study to ask another important question: can we allow ourselves to be seriously misled by active promotion of flawed data on important health matters?" Dr Brawley said.