Prostate Cancer Study: Update to PSA Screening Data Renews Controversy

Rationale for prostate cancer screening continues to be debated as an update to a large European trial reconfirms a reduction in death rates from prostate cancer in men who are screened for the disease. The study, however, found no significant difference in overall mortality between the two arms of the trial.

The most common screening tool is the prostate-specific antigen (PSA) test.

PSA screening has undergone intense scrutiny in the past few years

Part of the controversy stems from a US Preventive Services Task Force draft report from 2008 that suggests, based on analysis of the literature, PSA testing in asymptomatic men is not necessary.

The long-term results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) study, published today in the New England Journal of Medicine may help to clarify the utility of prostate cancer screening. The results show a 21% relative reduction in death risk from prostate cancer in men who were screened using the PSA test compared to those who were not (P = .001). In absolute terms, screening prevented 1 death among 1000 men who were randomized in the study. Median follow-up time for men in the study was 11 years. In the regularly screened group, 299 deaths from prostate cancer occurred compared to 462 in the control group, though overall mortality did not differ between the two study groups.

As Anthony Miller, MD, of the Dalla Lana School of Public Health at the University of Toronto, Canada noted in an accompanying editorial, the single death prevention came at the "considerable use of resources," and he points to contradictory findings in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, that he feels "are more applicable to the situation in the United States."

In the PLCO trial, 76,693 patients were randomized to receive either annual screening (PSA testing and digital rectal examination) or usual care. After 7 years of follow-up, there were 2820 incidents of prostate cancer in the screening group and 2322 incidents of prostate cancer in the control group, and there were 50 deaths in the screening group and 44 deaths in the control group.

Study Design

The multicenter ERSPC study enrolled men in 7 European countries between 1994 and 2003. Over 162,000 men between the ages of 55 and 69 were enrolled in the study and screened every 4 years (every 2 years in Sweden) using serum PSA levels and biopsy if the PSA value was found to be elevated.

One of the reasons for recommending against prostate cancer screening is the high chance for overdiagnosis and risk from potentially unnecessary biopsies that can cause complications. Additionally, men who undergo radical prostatectomy do not have a significantly better outcome compared with those who are assigned "watchful waiting." For example, the Prostate Cancer Intervention Versus Observation Trial showed that after 12 years, there was no significant effect on outcome between the invasive procedure and vigilant monitoring in men who have positive biopsies.

One question that remains is the effect of quality-of-life on men who have regular prostate cancer screenings and who may undergo biopsies as a consequence of detection of elevated PSA levels. "More information on the balance of benefits and adverse effects, as well as the cost-effectiveness, of prostate-cancer screening is needed before general recommendations can be made," concluded lead author Fritz H. Schrder, MD, department of urology at the Erasmus University Medical Center, and coauthors.

In his editorial, Dr. Miller notes the potential for treatment imbalance between the screening and control group that may account for the differential result, compared to previous prostate cancer screening trials. The men in the control group in the current study were not contacted directly, but instead, their records were reviewed in the cancer registry, unlike the screening group. Also, the men who were screened were more likely to be treated in an academic institution than the men in the control group, raising the question of whether they received better treatment.

"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," concludes Dr. Miller.

There are no consistent guidelines from the United States to Europe and even within European countries, recommendations vary. PSA testing is recommended annually in the United States, but the results reported for the ERSPC trial show that this level of frequency might be unnecessary. Monitoring once every four years may be adequate. Currently, prostate cancer screening is not recommended as a healthcare policy in any European country and therefore, there are no valid recommendations on a screening interval schedule, according to Dr. Schrder.

Dr. Miller also noted that before any practice-changing recommendations may occur based on these results, a detailed analysis of the balance between the study groups is needed. The ERSPC study is continuing.

"Our mortality curves show we may expect a larger difference in prostate cancer mortality between the arms and an increasing risk reduction of deaths from prostate cancer by screening," explains Dr. Schrder.

The crux of the matter is the balance between the positive and negative aspects to screening: the data in the current study seems to suggest screening does help to reduce death risk from prostate cancer in the long term, but the drawback is that there are still many overdiagnoses and unnecessarily aggressive treatment of slow-growing, not life-threatening prostate cancers. "The new data strengthen the argument for screening, but don’t resolve the issue," says Dr. Schrder.

Dr. Schrder believes that the patient, with the aid of his doctor, needs to make an educated decision for himself. "In the existing situation of uncertainty, decision making needs to be individualized. It is not the doctor but the potential patient who is confronted and who has to deal with the existing uncertainties. We as doctors have to assist in this matter by pointing out the up and down sides and providing decision aids."