PSA Screening: Still Useful After All These Years?

Charles P. Vega, MD; Gabriel A. Rivera, MD, MBA


August 13, 2015

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Should We Screen for Prostate Cancer at All?

Charles P. Vega, MD: I am Chuck Vega, a clinical professor of family medicine at the University of California, Irvine. Joining me today is Dr Gabe Rivera, a hematologist/oncologist in Fresno, California. We are going to discuss prostate cancer screening—a very controversial topic.

In 2012, there were about 240,000 cases of prostate cancer in the United States and more than 28,000 related deaths.[1] Men in this country have a 16.5% lifetime risk for prostate cancer.

When we think of prostate cancer screening, we typically think of the prostate-specific antigen (PSA) test. But that test has performed fairly poorly in two major trials. In the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial,[2]PSA screening was not associated with any mortality benefit—even in terms of mortality from prostate cancer itself.

The European Randomized Study of Screening for Prostate Cancer (ERSPC),[3]another trial that came out a few years ago, found a 20% relative risk reduction in prostate cancer deaths in association with screening. But it required a high number of men—1410, to be exact—to be screened to prevent one additional death due to prostate cancer.

The goal of cancer screening is not just to detect cancer, but also to prevent morbidity and mortality. My question is: Should we screen for prostate cancer at all?

Gabriel A. Rivera, MD, MBA: This is by far one of the more controversial screening tests, because you miss several prostate cancer diagnoses at the lower PSA values (eg, 2.0 ng/mL). The two studies that you mentioned used different cutoffs. The median cutoff was 3.0 ng/mL in the European trial and 4.0 ng/mL in the PLCO study. But regardless of the cutoff chosen, prostate cancer was still found on each end of the spectrum.

It comes down to the PSA level being a poor marker, but like mammography, it's what we have for now.

Being such a poor marker of prostate cancer, is PSA useful to clinicians at all? I think it is. Just like mammography to screen for breast cancer in women aged 40-49 years, screening with PSA is an individualized decision.

When a patient undergoes PSA screening, there are risks. That person might need a biopsy. There are also potential complications from procedures and treatments, including radiation. These risks are important, and the patient must ask himself, "Is this an indolent cancer that will not take my life? Will I pass away from something else?"

Physicians need to have very concrete, yet delicate, conversations with patients, letting them know that a low PSA value may be of little use, unfortunately, in determining whether they will have prostate cancer later in their lives.

The higher PSA values (≥ 10 ng/mL) are more concerning. According to the National Comprehensive Cancer Network (NCCN) guidelines,[4] a biopsy is recommended with those high levels, along with other risk factors. Age is the number one risk factor for prostate cancer, but ethnicity is another one and is a controversial area.

African Americans, in particular, have higher PSA values and a higher incidence of prostate cancer. These relationships, however, have not been well studied in a randomized controlled trial. That must be done to assess whether PSA screening is associated with a significant absolute reduction in mortality in this population.

Another risk factor is whether a patient is known to have BRCA1 and BRCA2. There is a slight increased risk with that. These risk factors can guide you, but there needs to be a discussion with the patient. Once he knows the risk factors, the patient must decide whether to go forward with testing.

It is probably reasonable to start screening men aged 50 years or older. Similar to breast cancer, you want to know that their life expectancy is greater than 5 years.

PSA as a Marker

Dr Vega: Yes; if there is a life expectancy under 5 years, we have to question the value of any cancer screening.

I am intrigued by the idea of using a PSA as a marker, because the sensitivity, although not perfect, is fairly good, particularly at the higher levels.

For patients with lower PSA levels, some observational research[5] shows that for men who are younger than 56 years and below the median for PSA levels, their risk of eventually developing metastatic prostate cancer is well under 1%.

Another study[6] looked at PSA screening in 60-year-old men. Those men who had a PSA < 2.0 ng/mL still had some risk of developing cancer, but their cancer-related mortality rates were quite low. Whereas for those men whose levels were above 2.0 ng/mL, the positive predictive value of continued screening became pretty high. And the number needed to screen was fairly low to detect prostate cancer. The number needed to screen was 23, and that was actually to prevent one additional death from prostate cancer.

If you have a patient who has gone through the decision analysis and has decided to get screened year after year and has PSA values that are repeatedly coming in the > 1 ng/mL but < 2 ng/mL range, you may want to consider discontinuing screening. That is because the data, which have only emerged in the past few years, suggest that this man's overall risk for any cancer that poses a threat to his well-being is fairly low over his lifetime.

This is the ultimate in shared decision-making. Because the US Preventive Services Task Force recommends against prostate cancer screening,[7] I leave it until the end of my health maintenance activities—a fairly long list when you include all the cancer screening, vaccinations, and other screens and checks that we are supposed to be doing for our patients. Prostate cancer screening comes last.

Prostate Health Myths

In my practice, I hear a lot of prostate health myths, particularly about libido and erectile function. Prostate cancer can contribute to erectile dysfunction, but many of these patients also have obesity, diabetes, hypertension, and many other risk factors for erectile dysfunction. Getting a PSA test is not necessarily going to put these patients on the road back to improved libido and sexual function. That is something worth watching for in practice.

When it comes to prostate cancer screening, are there any other practical pointers you can think of?

Dr Rivera: The digital rectal examination deserves a brief mention. There is no clear evidence for doing it. However, in many of these studies, the digital rectal exam was paired with a PSA level. The PSA by itself is good enough.

Also, there are certain factors of which you should be aware that can raise the PSA value. For example, acute prostatitis can cause a transient rise in PSA levels for about 48 hours, but you can still order it. If the patient has acute prostatitis or urinary retention, you may want to wait 6-8 weeks until the symptoms resolve and the antibiotic course is completed before checking a PSA level.

Hopefully, neither the clinician nor the patient will become alarmed if you happen to check it sooner. If indicated, you should probably repeat it at a later time.

Dr Vega: I would not do a digital rectal exam in an asymptomatic patient. These exams are not associated with much benefit, and there can be rare complications, such as abscesses or microtears. Unfortunately, the finger is not the most sensitive instrument!

We are not saying that there is no place for prostate cancer screening. Prostate cancer is a very serious disease that costs thousands of lives each year. It can be prevented with appropriate treatment initiated in a timely fashion. However, for the majority of men, the decision to get PSA screening is going to be made with their healthcare professional. We don't have the tools right now that move it to the top of the list in terms of health maintenance and promotion.

It is important to recognize the limitations of screening and to share those with patients so they can make informed decisions. Those are the important pieces for the foreseeable future.


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