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.

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