Two large prostate cancer screening trials led to different conclusions about the disease's impact on mortality: One found that screening reduces prostate cancer deaths by 20%, and the other found that it makes no difference at all.
The results were published online to coincide with a press briefing at the European Association of Urology Annual Congress in Stockholm.
The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial followed 77,000 men for up to 10 years and found similar rates of prostate cancer death among those randomized to regular screening with prostate-specific antigen (PSA) testing or to usual care (50 vs. 44 deaths).
Conversely, the European Randomized Study of Screening for Prostate Cancer (ERSPC), which included 182,000 men, found that routine PSA screening significantly reduced the rate of prostate cancer mortality, compared with usual care. But the savings come at a price, admitted primary investigator Dr. Fritz Schroder and his colleagues: More than 1,400 men would need to be screened and 48 additional cancers treated to save one life.
After reading the two studies, physicians and patients may be as confused as ever about balancing the risks of long-standing adverse treatment effects with the benefits of early diagnosis and treatment, Dr. Philip W. Kantoff said in a discussion sponsored by the New England Journal of Medicine.
“The deceptively simple PSA test inevitably leads to a cascade of biopsies, which lead to prostate-cancer diagnoses, leading to aggressive treatments for those prostate cancers, leading to men having substantial side effects from those treatments [including] urinary incontinence and sexual dysfunction,” said Dr. Kantoff, director of the Lank Center for Genitourinary Oncology at the Dana Farber Cancer Institute, Boston.
“And many of these men suffer those downstream troubles for a cancer that was never, ever destined to cause them harm in their lifetime,” he noted.
Dr. Michael J. Barry, who wrote an editorial that accompanied the papers, concurred. “The trade-offs reflected in these data, like beauty, will be in the eye of the beholder,” wrote Dr. Barry of Massachusetts General Hospital, Boston.
“Some well-informed clinicians and patients will still see those trade-offs as favorable, others will see them as unfavorable. As a result, a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever” (N. Engl. J. Med. 2009;360:1351–4).
From 1993–2001, PLCO randomized 77,000 men aged 55–74 years to either annual screening (PSA testing for 6 years and digital rectal exam for 4 years) or usual care, which sometimes included screening. The PSA cutoff for biopsy was 4 ng/mL.
Dr. Gerald Andriole and his colleagues reported outcomes after 7 and 10 years of follow-up (N. Engl. J. Med. 2009;360:1310–9). At 7 years, prostate cancer had been diagnosed in 2,820 in the screening group and 2,322 in the control group, a significant difference. At 10 years, there were still significantly more cancers diagnosed in the screening group (3,452 vs. 2,974).
At 7 years, 50 men had died from prostate cancer in the screening group and 44 in the control group—a nonsignificant 13% difference. By year 10, with data in for 67% of the subjects, 92 in the screening group and 82 in the control group had died—also a nonsignificant difference. The difference stayed nonsignificant when the data were analyzed by tumor stage or previous screening at baseline.
Although treatment-related complications arose, those data were not included. Instead, they are being analyzed as part of an upcoming quality of life study.
The authors noted that the lack of mortality reduction could be caused by improved prostate cancer treatment over the trial period or by the short follow-up time, which might not have been enough for all cancers to develop. “However,” wrote Dr. Andriole of Washington University, St. Louis, “We now know that prostate-cancer screening provides no reduction in death rates at 7 years and no indication of a benefit … by 10 years.”
ERSPC examined outcomes in 162,000 men aged 50–74 years who had been included in seven European health registries, wrote Dr. Schroder of Erasmus Medical Center, Rotterdam. Subjects were randomized to PSA screening once every 4 years or to no regular screening. The screening protocol varied by country; PSA cutoffs triggering more investigation ranged from 2.5–4 ng/mL (N. Engl. J. Med. 2009;360:1320–8).
Overall, screening nearly doubled the number of prostate cancers diagnosed (5,990 in the screening group vs. 4,307 in the control group). But the increased diagnoses carried a price. Of those who underwent biopsy for an elevated PSA, 76% had a false-positive result. The positive predictive value of a biopsy was also low—just 24% on average.