About those prostate-study numbers ...

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When the PSA test was developed in the early 1980s, researchers thought it would have a major effect on prostate cancer deaths, just as mammography did for breast cancer and the Pap smear for cervical cancer. Some hoped it would reduce deaths by 50% or more.

Conservative researchers thought its value should be proved in a clinical trial, but there were many objections. For one thing, such a trial would be costly and complex, involving tens of thousands of men. True believers argued that it would be unethical to withhold the screening from some patients because they ‘knew’ it would work. Some physicians urged African Americans not to participate in such a trial because they have an elevated risk of prostate cancer, so it is important that they get screened.

The American trial finally got under way in 1992 under the leadership of Dr. Gerald Andriole of the Washington University School of Medicine in St. Louis. (Here’s today’s story: Studies cast doubt on prostate cancer screenings.) Half the patients were given yearly PSA tests and digital rectal examinations. The rest were assigned to ‘normal’ care by their physicians; that care could include screening if the patient and his physician desired it. As a result, 40% of the men in the control arm received PSA screening in the first year of the study; by the end, 51% were receiving it, muddying the results. In a true controlled study, men in the control arm would not have received screening, but the researchers did not feel that could be justified ethically.

Men were subjected to biopsies if their PSA measured more than 4 or if they had an abnormality in the rectal exam, routine procedure in this country.

Dr. Andriole and his colleagues reported Wednesday in the online version of the New England Journal of Medicine that, at the end of 10 years, 17% more cancers were diagnosed in the screened group than in the control arm. There were 92 prostate cancer deaths in the screening group and 82 in the usual treatment group, a difference that was not statistically significant.

The study ‘basically confirms what we already know: Screening is not going to benefit anybody in the first five years,’ said Dr. S. Adam Ramin, a urological oncology specialist at St. John’s Medical Center in Santa Monica. ‘They didn’t follow the patients long enough to see a benefit.’

The study was halted prematurely because the Data Monitoring and Safety Board overseeing it found a continuing lack of evidence that the screening reduced death. The preliminary results also suggested that the screening was causing men to be treated unnecessarily.

A European study, led by Dr. Fritz H. Schroeder of Erasmus University in the Netherlands, was actually a compilation of data from seven trials, each of which had slightly different criteria. In general, the men in the screening group were screened less often -- about every four years, on average -- and were less likely to receive a rectal exam than men in the U.S. study. Few men in the control arm were screened because PSA testing is much less common in Europe.

And the threshold for biopsies was lower, usually a PSA reading of 3 to 3.5.

After nine years of followup, Schroeder and his colleagues reported a reduction in prostate cancer mortality of seven deaths per 10,000 men screened, a 20% reduction.

But the results were a ‘weak signal’ and ‘we don’t have 100% confidence in them,’ said Dr. Otis W. Brawley, chief medical officer of the American Cancer Society. He noted that a Swedish trial of treatment versus ‘watchful waiting’ showed a similar weak signal after 10 years, then no benefit after 12.

Moreover, the 73,000 men in the screening group underwent more than 17,000 biopsies, which are painful, expensive and fraught with complications. For those who undergo treatment, complications are more severe, including impotence and incontinence in men who have surgery and rectal and bladder irritation from radiation. The surgery also has an 0.5% death rate.

And clearly, Brawley added, many of those men who were treated would die with their cancers, not from them. ‘We’re curing men of cancers that don’t need to be treated,’ he said.

-- Thomas H. Maugh II