A Second Look at the European Randomised Study Of
Screening For Prostate Cancer

Last week, The Lancet published 13-year follow-up results from the European Randomised study of Screening for Prostate Cancer (ERSPC), an international trial of PSA testing in seven countries (the Netherlands, Belgium, Sweden, Finland, Italy, Spain, and Switzerland). (Unfortunately, the complete study is behind a paywall.) The core finding reported was that after 13 years of follow-up, prostate cancer screening cuts deaths by about 20%. However, the investigators concluded that screening should be rejected pending “further quantification of harms,” with their elucidation “a prerequisite for the introduction of population-based screening.” Fair enough.

Even though the results were covered by more than 100 news outlets internationally, absent from the many reports were critical questions about the trial that speak to the trustworthiness of the findings. Study limitations were also given short shrift by the trial investigators and the editorialists.

In proceeding with this story, I learned first hand that even though outsiders reviewing the study pinpointed flaws, they placed near the top praise for the study’s conclusion, that screening be looked at skeptically, based on the knowledge base today.

Here, I take the liberty of sharing the pitfalls, believing that for patients to view screening without bias, honest communication, however complicated, is imperative.

What I learned about the trial sure startled me.

Just Two of Seven Countries Showed a Screening Benefit

Reviewing the trial for PatientPOV.org, Anthony Zietman MD, immediate Past President of the American Society for Radiation Oncology, and Professor of Radiation Oncology at Harvard Medical School, raised this question:

“An unexplained aspect of this multinational study is that the “benefits” of screening were seen in Holland and Sweden, but not in any of the other half dozen European nations contributing patients. Explain that if you can! I know I can’t.”

In an email, Peter Albertsen, MD, Professor of Surgery, University of Connecticut Health Center, Farmington, CT, explained it this way:

“Swedes have a very high incidence of prostate cancer –higher than the rest of Europe and equivalent to US African-Americans. Screening works better the higher the incidence of disease. The Holland study was barely statistically significant. Some have argued that the screen detected cases were treated more aggressively. The big question is Finland. They contributed the most patients, but screening made no difference. They took a population-based approach, rather than Holland that invited men to participate before enrolling them in the study. In all the other countries, the sample sizes were too small. Therefore there was insufficient statistical power.”

American Cancer Society Chief Medical Officer Otis Brawley, MD, amplified issues surrounding the findings in Finland. Like Albertsen, he pointed out that the Finnish component of the trial was negative. “It was the largest part of the trial and Finns have a high rate of prostate cancer as well.”

In addition to the pitfalls noticed above, Brawley said:

Sweden had an unusual non-straightforward randomization that biases toward a finding that screening works. The control group was never informed that they were in a clinical trial. They randomized census rolls. This means that men with metastatic disease at the time of randomization on the screen arm got to opt out, while men in the control arm did not.

Moreover, Brawley questioned whether those in the control arm had the same access to quality of care as the screened arm:

“The screened individuals were treated by experts running the study. The control group got whatever was in the community.”

Brawley considers some of the issues in the trial so troubling that he has called for independent external review of the trial.

Praise for Investigators Opposition to Screening

Opposition to population-based screening has grown in recent years and commentators in this story praised the study’s conclusion as well. In an email, Brawley wrote:

“I agree with that [the conclusion] and it’s consistent with a number of current recommendations, including the American Cancer Society and the US Preventive Services Task Force, which are against ROUTINE screening, but speak positively toward true informed decision-making. The benefits are possible, but are small if they exist, as several studies have shown.”

Albertsen added:

“This study and the recent SPG-4 [Scandinavian Prostate Group 4] results are actually quite consistent.  PSA testing does find some prostate cancers that are eventually fatal.  Radical prostatectomy does cure some prostate cancers that would have been fatal. But in the process of detecting these cancer, a large proportion will not progress, hence overtreatment occurs. In addition, when doctors find very aggressive cancers, they are especially lethal and treatment does not alter outcome. So screening works for some cancers, but not for others.  Now the problem is how to tell these two groups apart.”

Nonetheless, rejection of prostate cancer screening remains a bitter pill for many Americans to swallow. Some question whether they are trading a risk for death from cancer with harms that they think simply don’t compare.

There’s plenty more that has to be done if doctors and patients are going to get on the same page. A lot of work is underway to engage patients, share evidence-based data, and ratchet up understanding of the benefits, risks, and uncertainties.

These are complex issues and they don’t fit well into a simple slogan or headline. In writing posts like this, sharing what I hear patients saying about these issues, I hope to help bridge some of the gaps in understanding, further best care, and set in motion making informed choices.

NOTE: This post is the first of a series. There is a lot to discuss and I am interested in hearing from patients interested in these issues. I’ll try to get the next installment out before my summer vacation, but it may lapse until after Labor Day.

I invite you to comment below, tweet the link to the story, ask me about this on twitter @lauranewmanny, and by all means, like my Facebook page and discuss this there, and/or in comments below . I’d like to engage you all in further discussion.

With Prostate-Specific Antigen (PSA) Screening Questioned, Why Not Hurl Out the Next Unproven Prostate Tests?

The headline in the New York Times story this morning, “New Prostate Cancer Tests Could Reduce False Alarms,” by Andrew Pollack, had me scratching my head. Had I missed something in the story of advances in prostate cancer screening and diagnosis? The search for finding something better than PSA tests to reduce false positives and unnecessary biopsies has been going on for time immemorial, or more accurately, maybe the last 15 years. Also, separating the lethal from the cancers that amount to no trouble at all has also been a key research question.

Had The Times been bamboozled into a story by industry copywriters and urologists, hoping to bring back attention to the prostate? Clearly, the US Preventive Services Task Force, the American Cancer Society, and other groups stomped on routine prostate screening. Plenty of thought leaders agreed it is not a good prostate cancer screening test.

It’s also not just screening of asymptomatic men that is at issue. What about the men diagnosed with prostate cancer? Can they be better stratified so that men with lethal cancers are separated from those that require no treatment?

The New York Times article waxes poetic about the “more than a dozen companies that have introduced tests or are planning to in the near future.” It moves on to the transformative potential of molecular markers and a high-stakes battle looming ahead between Genomic Health and Myriad Genetics.

Are readers supposed to be wowed? I think so.

My favorite line in the story was this one:

“Some experts say that even if the new tests are not perfect, they are better than what is available now.”

Was The Times in the dark about thought leaders who thought all this is premature, urologic oncologists included? Apparently. Will more men and their loved ones insist on these unproven tests? Most likely.

I don’t dispute that we need a good test that separates the bad cancers, but the test is not here yet. The data is thin.

On the Urology Workforce, Targeted Screening,
And the US Preventive Services Task Force

It is abundantly clear that the US Preventive Services Task Force Draft Guidelines on Prostate Cancer Screening will not be welcome news to many urologists. I have attended numerous annual meetings of the American Urological Association, the physician organization for urologists. The majority of papers  concern that walnut-shaped gland, the prostate, usually taking up prostate cancer or an enlarged prostate, AKA BPH (benign prostatic hyperplasia). Some urology practices focus  exclusively on the prostate. Urologists will need to readjust.

As one doctor who has nothing to do with the US Preventive Services Task Force told me: “There is plenty of honest urology for them to practice….stones, incontinence, kidney cancer etc. But even in the world of prostate cancer a good 20% to 30% of patients have bad enough disease that they deserve attention and, perhaps, more of it than they have been given in the past due to the crazed gold rush towards the low-risk men.” I agree totally with this statement. If Americans could vote with their feet, I think too that they would want urologists to treat the truly important areas in urology, rather than a disease that the odds are will not cause trouble for most men.

Jeez, it would be welcome news if the public understood this and if it was talked about more openly. As a reporter, I have witnessed the fleeing of docs from real medicine to cosmetic surgery and the rich. How refreshing it would be if urology began to turn out more doctors that patients need.

On another note, the Draft Recommendations that will be released officially tomorrow are expected to address concerns of high-risk individuals. The word is out that there will be a call for research into whether or not there should be targeted screening. In other words, should high-risk men (e.g. because of family history) be screened, and at what intervals? That should come as some comfort to people who worry that the high risk will be lumped into one healthy asymptomatic category.

The comment period begins after the official release tomorrow. If you have thoughts about the draft recommendations, positive or negative, get them on the public record. There’s plenty that patients and the public  will want to mull over. Ask questions and don’t leave it to someone else.  I’ll be following this issue, providing follow-up links on where to send your comments, and more.