The Life-Saving Benefits of PSA Screening

Two Studies:

ERSPC and PLCO

The Spring 2009 issue of Quest was devoted to the subject of prostate cancer screening in response to the high interest in the topic created by the publication of two studies in the New England Journal of Medicine. (Articles from that Quest are available on the URF website: www.drcatalona.com)

The European Screening Trial (ERSPC) provides conclusive evidence that PSA screening can save lives; whereas, the United States trial (PLCO) essentially contains no useful information.

Moreover, it is likely that the mortality benefit in ERSPC is an underestimate because of the relatively short follow-up, the relatively long screening interval, the non-use of digital rectal exam as a screening test after the first round, and contamination in the control arm.

In contrast, it is unlikely that the misleading PLCO results will change substantially with further follow-up because the study was fatally flawed from the beginning. The basic flaws included:

1. 43% of the study group was prescreened, eliminating high-risk Prostate cancer from the study population.

2. 52% of the control population was screened during the study thereby contaminating the actual results.

3. No requirement was made for men with abnormal screening results to undergo biopsy and only 40% of those identified did, thus compromising early detection and treatment

4. It takes patients about 13 years after recurrence following a radical prostatectomy to die of prostate cancer, but the median follow up for men with cancer in the PLCO was 5-6 years, insufficient to evaluate mortality results and

5. Men were included up to age 74 and they are less likely to have a mortality benefit from screening.

Dr. William J. Catalona

I Recommend PSA Screening

I continue to recommend PSA screening to my patients. PSA testing provides the best estimate of risk for having prostate cancer and the greatest chance of avoiding death from this disease.

PSA screening has been widely accepted in the United States and many other countries because it works.

Patients and physicians who are concerned about decreasing the death rate from prostate cancer have relied upon the test because it gives them valuable information and because death rates have continued to fall during the PSA era.

Although the PSA test is not perfect, it is effective in identifying men at high risk for prostate cancer and for detecting it early. Moreover, a strong correlation exists between PSA and aggressive forms of the disease.

Decrease in Advanced Stage Diagnosis

During the PSA screening era in the U.S., there has been an 85% decrease in the percentage of prostate cancer cases that present with advanced-stage disease and a 40% reduction in the age-specific prostate cancer mortality rate.

Similar trends have been reported from the World Health Organization Database in countries that have adopted PSA screening but not in those that have not. These impressive trends would not have occurred if screening detected only harmless cancers.

Screening Makes Treatment More Effective

Early detection would be useless without effective treatment.

The most effective curative treatment, radical prostatectomy, was available before the PSA era, but this treatment didn’t show falling death rates until PSA testing was implemented.

Curative treatments are effective mainly in patients with early disease, which is why the most important factor responsible for the falling death rates is PSA screening.

Cure Is the Goal

The physician’s job is to ensure that patients receive effective, high-quality treatment to maximize cure rates and minimize side effects.

Goal of Screening

The goal of screening is to detect cancers that could cause suffering and death, but screening may also detect cancers that would never cause symptoms. Currently, because of limited ability to distinguish between harmless and lethal cancers, most cancers are treated.

Over-diagnosis Is Minimal and Inevitable

Some “over-diagnosis” and “overtreatment” will occur with early detection screening, but research on my 5,000+ patients shows it is minimal compared to the “underdiagnosis” of prostate cancer.

To date, no validated test is superior to PSA as a screening device. There is always hope that the PSA test, itself, may be further refined or some other test discovered that would be even more precise. The intelligent use of such tests could certainly diminish, but never completely eliminate, some over-diagnosis and over-treatment.

Presently, no one is able to predict the aggressive or non-aggressive traits of diagnosed prostate cancer. Which patients or doctors would choose to play a game of Russian Roulette with the diagnosis of prostate cancer when so many men die from it?

Letter From Patrick C. Walsh, MD:

Prostate Cancer Testing Is Best Option
for Men

Until an alternative exists, prostate cancer testing is the best option we have to allow men to make an informed decision. Disparaging testing does a great disservice. Because prostate cancer produces no symptoms until it’s too far advanced to cure, as appropriate, men should have a PSA test and examination.

In 1990, before PSA testing, only 68% of newly diagnosed men had localized cancer and 21% were metastatic.

Today, 91% are diagnosed with localized disease and only 4% have metastases.

With the ability to diagnose cancer earlier and treatment advances, U.S. deaths from prostate cancer have fallen 40% in ten years, a greater decline than for any other cancer.

Today, men have a choice that once did not exist: Undergo testing and, if there is cancer, make an informed choice for treatment or observation, or do nothing and run the risk of a diagnosis until it’s too late.

I choose to know.

*Patrick C. Walsh, M.D. is the University Distinguished Service Professor of Urology at the James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions

Under-diagnosis Needs More Attention

“Under-diagnosis” and “under-treatment” are important concerns that have received much less attention than “overdiagnosis” even though they have life-threatening consequences.

“Under-diagnosis” and “under-treatment” occur when prostate cancer is not detected until it has spread beyond the prostate and when that unnecessary delay in treatment prevents a cure that would have been the result of earlier treatment.

Research on my 5,000+ patients shows “underdiagnosis” is more of a concern than “over-diagnosis.”

Concern Over Active Surveillance

Active surveillance and focal therapy have emerged as strategies to guard against over-treatment; however, physicians should be careful not to throw out the baby with the bath water.

With active surveillance (also known as “watchful waiting”) or focal therapy (also known as “the male lumpectomy”), potentially life-saving treatment may be delayed in patients with initially under-graded or understaged tumors. Some will slip through the cracks and have unnecessary suffering and death from prostate cancer.

Dr. Catalona at a recent meeting with Dr. Fritz Schroeder.

Dr. Schroeder, who led the European Randomized Study on Screening for Prostate Cancer (ERSPC), began his interest in the study after he was introduced to Dr. Catalona’s work on PSA testing for early detection.

“In 1990,when Dr. Catalona was our visiting professor at Erasmus University in Rotterdam, I saw the data that he would soon publish in the New England Journal of Medicine, which showed that PSA testing led to the earlier diagnosis of curable disease. This inspired me to initiate pilot studies,” he said.

Those studies culminated in the landmark ERSPC.