PSA Screening Reduces Death From Prostate Cancer

Roxanne Nelson

March 14, 2012

March 14, 2012 — There is a great deal of controversy about whether routine prostate-specific antigen (PSA) testing reduces prostate cancer mortality. That controversy became more intense after a draft recommendation issued by the US Preventive Services Task Force (USPSTF) advised against routine screening of the general population.

However, the updated results of a large randomized European trial have confirmed a previous finding that PSA-based screening significantly reduces mortality from prostate cancer. The updated results, published in the March 15 issue of the New England Journal of Medicine, demonstrate a relative risk reduction of 21% with prostate cancer screening in the intention-to-screen analysis.

The initial analysis from the European Randomized Study of Screening for Prostate Cancer (ERSPC), was reported after 9 years of follow-up. The update has added 2 more years, for a total of 11 years of follow-up.

Tale of 2 Studies

This follow-up analysis confirms that screening reduces prostate-cancer-specific mortality but not all-cause mortality.

However, "to prevent 1 death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected," explains Anthony B. Miller, MD, from the Dalla Lana School of Public Health, University of Toronto, Ontario, Canada, in an accompanying editorial.

In addition, he describes conflicting results from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A recent update of that trial (J Natl Cancer Inst. 2012;104:125-132) confirmed the previous finding of no reduction in prostate cancer mortality with screening.

There are several possible reasons for the contradictory results, he writes, including differences in population size, screening interval, and cutoff for a positive PSA test (lower in ERSPC). But a fundamental issue is how the screening-detected cancers were treated in the 2 studies.

In the screening group in the ERSPC, men diagnosed with prostate cancer were more likely to have been treated at an academic center than control subjects. So men in the screening group could have received better treatment, which could have had a major effect on outcome, he suggests.

"Reconciling the ERSPC results with those of the PLCO trial is difficult," writes Dr. Miller. "Before accepting these results to guide policy, we need further clarification as to what actually happened in the trial, especially with respect to treatment, and confirmation that the 2 study groups were balanced," he notes.

The PLCO trial seems to indicate that adding organized screening to opportunistic screening will have no benefit but will increase adverse effects, such as false-positive screening tests, unnecessary biopsies, overdiagnosis, and impaired quality of life, explains Dr. Miller.

In the ERSPC, 13% of the screening tests were false positives, compared with 7% in the PLCO trial, and 76% of biopsies in the ERSPC did not result in a prostate cancer diagnosis, compared with 62% in the PLCO trial. Additionally, rates of overdiagnosis were about 50% in the ERSPC and 17% to 30% in the PLCO trial.

"We are left with an unsatisfactory situation, in which many practitioners will think there are insufficient data to recommend abandoning PSA screening for prostate cancer," Dr. Miller concludes. "However, the findings of the PLCO trial are more applicable to the situation in the United States, since the ERSPC was conducted in a largely PSA-naive population."

"Therefore, an intensification of PSA screening would be unwise, and I think it would be advisable to follow the preliminary recommendations of the US Preventive Services Task Force," he adds.

No Recommendations Made Yet

Despite the reduction in prostate-cancer-specific mortality, the ERSPC investigators note that more information is needed on the balance of benefits and adverse effects and on cost effectiveness before general recommendations can be made on screening for prostate cancer.

"I do not believe that there is a case for population-based screening in men of any age," explained lead investigator Fritz H. Schröder, MD, professor of urology at Erasmus University, Rotterdam, the Netherlands. "Balanced information and informed decision making is essential for everyone."

This information needs to be included in conversations between men considered to be at high risk and their doctors, he told Medscape Medical News.

Dr. Schröder agrees that more research is needed to balance the risks and benefits, but notes that their data do contribute to the "pro side" of the controversy. "This is because a doctor can now state with more conviction and certainty, if you decide to be screened, how your chance of death from prostate cancer is decreased in a significant way," he said.

Study Details

The ERSPC involved 182,160 men 50 to 74 years of age at study entry from 8 European countries. There was a predefined core age group of 162,388 men 55 to 69 years of age.

Participants were randomized to either PSA screening or no screening, and the primary outcome was mortality from prostate cancer.

The median screening interval was 4 years. In the screening group, 6963 prostate cancers were diagnosed (cumulative incidence, 9.6%), as were 5396 in the control group (cumulative incidence, 6.0%). There were approximately 1000 more cases of prostate cancer in each study group than in the previous analysis.

There were 299 deaths from prostate cancer in the screening group and 462 in the control group (mortality rate, 0.39 vs 0.50 per 1000 person-years). The rate ratio was 0.79 (95% confidence interval [CI], 0.68 to 0.91; P = .001), which corresponded to a relative risk reduction of 21%, in favor of PSA screening.

In addition, there was an absolute difference in mortality of 0.10 deaths per 1000 person-years, or 1.07 deaths per 1000 men randomized. After correction for selection bias and noncompliance, the authors found an adjusted rate ratio of 0.71 (95% CI, 0.58 to 0.86; P = .001) for screened men, corresponding to a 29% relative risk reduction.

The rate ratios for years 1 to 9 was 0.85 (95% CI, 0.71 to 1.03) and for years 1 to 11 was 0.79 (95% CI, 0.67 to 0.92).

Screening did not lead to a decrease in overall mortality, which was similar in the screened and control groups (18.2 vs 18.5 per 1000 person-years; rate ratio, 0.99; 95% CI, 0.97 to 1.01).

Dr. Schröder reports serving as a board member of European Urology; receiving consulting fees from GlaxoSmithKline and Ferring; and receiving lecture fees and travel support from GlaxoSmithKline, Ferring, Société International d'Urologie, and the European Association of Urology. His coauthors report their financial relationships in the paper. Dr. Miller reports receiving funding for consultancy from the US National Cancer Institute and the Canadian Partnership Against Cancer.

N Engl J Med. 2012;366:981-990, 1047-1048. Abstract, Editorial

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