PSA Screening Does Reduce Deaths, but Is Not Recommended

Roxanne Nelson

August 06, 2014

Routine prostate-specific antigen (PSA) screening for prostate cancer does save lives: the updated results from the European Randomised study of Screening for Prostate Cancer (ERSPC) confirm that there is a substantial reduction in prostate cancer mortality attributable to PSA screening.

The updated results were initially presented in April at the European Association of Urology 29th Annual Congress and have now been published in the Lancet.

However, despite these findings, the authors remain cautious about population-based screening programs, because the high rate of screening-related overdiagnosis and overtreatment still needs to be addressed.

"The time for population-based screening has not arrived," commented lead author Fritz Schröder, MD, a professor of urology at Erasmus University Medical Center in the Netherlands. There is no population-based PSA screening in Europe, although there has been widespread use of PSA for screening for prostate cancer in the United States.

"Further research is urgently needed on ways to reduce overdiagnosis, preferably by avoiding unnecessary biopsy procedures, and reducing the very large number of men who must be screened, biopsied, and treated to help only a few patients," Dr Schroder said in a statement.

These sentiments are echoed by the authors of a linked commentary. Ian Thompson, MD, at the University of Texas Health Science Center, San Antonio, and Catherine Tangen, PhD, at the Fred Hutchinson Cancer Research Center, Seattle, Washington, comment that "the new findings from ERSPC are crucially important," but they add that at present, PSA screening is imperfect. Aside from detecting cancers that will never be life threatening or causing patients to undergo unnecessary treatment, they point out that "an often-overlooked issue with screening is that it does not prevent all disease-related deaths."

"It is this trio of drawbacks (overdetection, treatment complications, and disease progression) that leads to the uncertainty about the role of screening," they write.

They hope that an "improved understanding of prostate cancer might tip the balance towards increased use of screening."

"In future publications from the study, the distribution of prostate cancer deaths by Gleason score and PSA at diagnosis will be important to understand how to tailor screening and treatment," the editorialists add.

Long Follow-up Data

Routine screening for prostate cancer has been heatedly debated for about 20 years, and the question of whether the practice does more harm than good has been muddied by unclear data on whether there is a mortality benefit.

The EPSPC has previously shown that PSA-based screening does reduce mortality from prostate cancer, but these results conflict with the results of the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which found that screening does not reduce deaths from the disease.

The ERSPC reported its first results after 9 years of follow-up, and then an update added 2 more years, for a total of 11 years of follow-up. The current article now reports on 13 years of follow-up.

The ERSPC began in 1993 and included men between the ages of 50 and 74 years from 8 countries (Belgium, Finland, France, Italy, the Netherlands, Spain, Sweden, and Switzerland) who were randomly assigned to receive either PSA screening every 4 years (2 years in Sweden) or no intervention. Participants were referred for biopsy if their PSA concentration was higher than 3.0 ng/ml.

A total of 182,160 men were included, with a predefined core age group of 162,388 men 55 to 69 years of age. Of this group, 145 died between randomization and screening. At 13 years' follow-up, 7408 prostate cancer cases were diagnosed in the screening group, and 6107 cases were diagnosed in the control group.

Among the screened men who underwent a biopsy, 4883 (24.2%) were diagnosed with prostate cancer within 12 months after testing.

The incidence of prostate cancer was 9.55 per 1000 person-years among screened men and 6.23 in the control group, and at 13 years, related mortality was 0.43 per 1000 person-years in the intervention group and 0.54 per 1000 person-years in the control group (rate ratio [RR], 0.79; P = .001). This rate is similar to that reported at 11 years, note the authors.

After making adjustments for nonparticipation, there was an RR of 0.71 (P = .001) after 11 years and 0.73 (P < .0007) after 13 years.

Screening appeared to reduce prostate cancer deaths by 15% (RR, 0.85) at 9 years, and this improved to 22% (RR, 0.78) at 11 years. At the 13-year follow-up, no further improvement in the relative reduction in prostate cancer mortality was observed (21%; RR, 0.79).

But importantly, the authors write, the number needed to invite to be screened to prevent 1 death declined from 1410 at 9 years to 781 at 13 years. Similarly, the number needed to detect cancer fell from 48 to 27, which demonstrated continuing improvement in the absolute effect of screening.

Expensive Public Health Disaster

However, the scientist who discovered PSA in 1970 says its use for routine screening has been a "hugely expensive public health disaster." Richard Ablin, PhD, research professor of immunobiology and pathology at the University of Arizona College of Medicine in Tucson, has publicly expressed his views before, such as in a New York Times opinion piece. He lamented that PSA was never meant to be used for routine screening, because it cannot detect prostate cancer. He pointed out that infections, over-the-counter drugs such as ibuprofen, and benign swelling of the prostate can all elevate PSA levels. More importantly, the test cannot differentiate prostate cancer that is rapidly growing and potentially fatal from cancer that is growing slowly and will not kill.

Now Dr. Albin has come out with a new book, The Great Prostate Hoax: How Big Medicine Hijacked the PSA Test and Caused a Public Health Disaster (Palgrave Macmillan, March 2014), which he says "exposes how the PSA test was illegally promoted by Big Pharma and misused for profit by Big Medicine, leaving countless millions of men with life-altering side effects from unnecessary treatment."

"Men and their families need to know of this book and the tragedy of over millions of men by those who have placed greed over patient care," he told Medscape Medical News.

Each center had its own funding responsibility. Several of the coauthors have declared potential conflicts of interest, as noted in the article.

Lancet. Published online August 7, 2014. Abstract


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