PSA SCREENING DOES MORE HARM THAN GOOD

AMSTERDAM — To the ongoing debate over whether routine screening for prostate cancer reduces prostate cancer mortality comes a new analysis that suggests that it does more harm than good.

The total harms that men experience in terms of impotence, incontinence, and other side effects from prostate cancer treatment can severely affect their quality of life, lead author Mathieu Boniol, MD, said here at the European Cancer Conference 2013 (ECCO-ESMO-ESTRO).

Dr. Boniol and colleagues conducted a systematic review of the literature for data on results of prostate-specific antigen (PSA) testing, biopsy rates, and mortality/associated side effects from radical prostatectomy, as well as hospitalization rates associated with biopsy. They also used data from the European Randomized Study of Screening for Prostate Cancer, which is the study showing the most favorable outcomes for PSA screening.

Overall, they found that the harms outweigh the benefits on a population level. This should further discourage the use of routine PSA testing for prostate cancer in the general population, Dr. Boniol said.

He did acknowledge, however, that there are high-risk groups, such as men with a family history of aggressive disease, who can benefit from PSA testing.

"Presently, we do not know if PSA screening decreases mortality," said Dr. Boniol, who is research director at the International Prevention Research Institute (IPRI) and a professor at Strathclyde Institute for Global Public Health at IPRI, Lyon, France. "We have conflicting data. It may save lives, but is testing helpful in the general population?"

The United States Preventive Service Task Force (USPSTF) recently recommended against routine screening with PSA for men who are symptomatic. However, this recommendation has invoked a great deal of controversy and disagreement among physicians and professional organizations.

In Europe, screening varies considerably from country to country, because there is no standard policy across the continent. But Dr. Boniol stated that PSA testing was widely implemented in France, where 55% of men between the ages of 55 and 69 years received PSA testing. He pointed out that family doctors routinely add PSA when ordering routine blood work.

"In France, a large proportion of men are receiving this test," he said during a press briefing. "More than 80% of men aged 65 years have received a PSA test during the past 3 years."

Dr. Boniol emphasized that according to statistics, PSA testing has not lowered prostate cancer mortality. In the 1980s, before the advent of testing, the incidence of prostate cancer in France was 5%, and disease-specific mortality was 2%.

But in the era of testing, he explained, incidence is now 14%. "But the risk of dying did not go up, it is still 2%."

"We are now finding cancers that never would have appeared in these men," he said, pointing out that upon autopsy, about 70% of men have changes in the prostate that are indicative of cancer, but it is disease that never would have been fatal.

Harms Outweigh Benefit

Dr. Boniol and colleagues estimated the total harm that men would endure if exposed to PSA testing by applying different side-effect estimates to a virtual population of 1000 individuals aged 55 to 69 years. They also included a group of 1000 unscreened men as a control group.

Under the best scenario from prostate cancer screening efficiency, the prevention of 1 death from prostate cancer is associated with a significant additional adverse event burden from undergoing biopsy and from the treatment of the diagnosed disease. These can severely affect the patient's quality of life and argue against using PSA for mass screening, they say.

In a group of 1000 men, the authors estimated that there will be 116 biopsies and 60 cases of prostate cancer. Overall, there will be 119 deaths in this population, of which 5.17 would be as a result of prostate cancer. In the population exposed to screening, there would be 270 biopsies performed and 96 prostate cancers diagnosed.

The mortality would be similar, with 191 deaths overall and 4.1 from prostate cancer. For 1 cancer death to be prevented among 1000 men, there would have to be an additional 154 biopsies, of which 9 would require hospitalization for severe adverse events; another 0.2 deaths would result from biopsy complications.

There would be 35 additional prostate cancers diagnosed primarily from low-risk men (32 cases). These cases would be associated with 12 additional cases of impotence, 2 cases of incontinence, and 1 case of fecal incontinence.

The authors note that a high percentage of prostate cancer–related surgery (18%) was performed on men who were older than 70 years. In addition, 183 deaths (0.15%) occurred 60 days after prostate cancer surgery. The overall risk of dying was 0.11% for men aged 40 to 69 years, and this number jumped to 0.36% for those 70 years or older 60 days after surgical intervention.

Awaiting a Tiebreaker

Breast, colorectal, and cervical cancers have well-established screening programs, and prostate cancer could benefit from a similar program because it is a very common cancer, commented Jack Cuzick, PhD, professor of epidemiology at the Wolfson Institute of Preventive Medicine at Queen Mary University of London, United Kingdom.

Dr. Cuzick gave a related talk on prostate cancer screening during European Cancer Conference 2013.

He reminded the audience of the 2 major trials that gave conflicting results as to the benefit of screening. The ERSPC (European Randomized Screening for Prostate Cancer) showed that routine screening lowered prostate cancer mortality, whereas the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) did not show an effect.

Although a number of reasons have been suggested to explain the differences between the 2 trials, Dr. Cuzick noted that a large, currently ongoing trial "may be the tiebreaker."

The UKCAP/PROTECT trial includes 450,000 men and is expected to report its findings in 2016.

"One of the real challenges, and in my mind, the major challenge that has to be resolved before we can really embrace screening is to separate the indolent from aggressive cancers," said Dr. Cuzick. "There is a crucial need to identify which cancers are likely to be fatal, and new molecular markers are needed."

"In countries like the US, where screening is done routinely, the incidence is almost 8-fold higher than mortality, so if you have prostate cancer, there is little chance of dying from it," he continued. "Yet most of these men are having radical treatment. If we can identify which men are likely to benefit from radical treatment accurately, we might be able to get those gains from screening, without overtreatment."

Offering his own opinion, Dr. Cuzick concluded that he does not think we will be ready for prostate cancer screening in the general population until better markers are established.

The study was funded by the International Prevention Research Institute, Lyon, France.

European Cancer Conference 2013 (ECCO-ESMO-ESTRO). Abstract 1481. Presented September 30, 2013.