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Prostate Cancer Screening: Beyond the PSA Test

Weigh the pros and cons of screening, and ask about new options that may better gauge your risk and guide treatment decisions.

There may be no aspect of men's healthcare more controversial than prostate cancer testing.

Proponents say screening with prostate-specific antigen (PSA) blood tests and other methods saves lives because it detects prostate cancer at an earlier, more curable stage. Opponents note that screening can lead to complications from invasive biopsies and treatment of tumors that may never threaten a man's life.

For the most part, routine prostate cancer screening is no longer recommended for all men. Rather, experts advocate engaging in shared decision-making with your physician, carefully reviewing the pros and cons of prostate cancer screening before saying yes or no.

As part of that process, a Cleveland Clinic expert recommends discussing newer tests that may augment PSA's predictive power, refine screening, and help guide subsequent decisions about biopsy and (if necessary) treatment.

“PSA is not going away. It's the backbone of everything we do still,” says Eric A. Klein, MD, chairman of Cleveland Clinic's Glickman Urological & Kidney Institute. “Talk to your doctor about screening, and if you decide to be screened, ask about these other tests.”

Prostate cancer screening should be limited to men more likely to gain benefits from it, namely those with a life expectancy of at least 10 years and high-risk groups: African-Americans and men with a personal or family history of prostate cancer. Most medical organizations recommend that men begin discussions about screening around age 50 or 55 (and younger for high-risk groups).

When deciding on screening, consider your individual risk, based on your age, race and family/personal history of prostate cancer, Dr. Klein says. Take into account whether and how you would want to treat a cancer if it were found, weighing the risks of monitoring the cancer and delaying treatment (active surveillance) versus the risks of urinary and sexual side effects associated with surgery or radiation treatments.

“Based on the available evidence, I recommend a baseline PSA for men starting at around age 50, with the timing of follow-up PSAs based on the initial level and individual risk factors (such as family history),” Dr. Klein says. “I also recommend that men who reach age 60 with a PSA of less than 2.0 ng/mL no longer need to be screened.”

Elevated PSA levels may result from prostate cancer or non-cancerous conditions, such as benign prostate enlargement or infection. So, the PSA test cannot accurately predict which men have prostate cancer, nor can it distinguish fast-growing, aggressive tumors from those that may not require treatment.

So, researchers have developed tests to complement the PSA and better predict which men will have clinically significant prostate cancer, potentially reducing the number of unnecessary biopsies and treatment. One of these tests, the Prostate Health Index (PHI), measures a PSA precursor protein known as [-2] pro-PSA along with other PSA types. The PHI blood test is indicated for men with a PSA level of 4 to 10 ng/mL, a prognostic gray area that may prompt many doctors to consider recommending a prostate biopsy.

Another test measures prostate cancer antigen 3 (PCA3) a gene specific to prostate cancer. A urine-based test, the PCA3 assay is indicated for men who have had a negative biopsy but still have elevated PSA levels. But, research suggests that PCA3 also may be useful in guiding decisions about an initial biopsy.

“We use PCA3 for patients who come in before an initial biopsy with worrisome PSA levels, in the 3 to 7 [ng/mL] range, when we're not sure whether that indicates noncancerous prostate enlargement or prostate cancer,” Dr. Klein says. “If the PCA3 is low, we generally don't biopsy them. If the PCA3 is higher, we would proceed with biopsy.”

Dr. Klein and colleagues also have begun using a newer tool for predicting prostate cancer and reducing the number of biopsies: the 4K Score. The test measures PSA and other prostate-derived proteins and combines them with other patient characteristics to calculate the likelihood of finding high-grade prostate cancer on biopsy.

“4K can give a more precise estimate about whether you're likely to harbor a Gleason 7 or higher cancer,” Dr. Klein says. “If you are, that would justify doing a biopsy.”

The 4K Score and genetic tests like the Oncotype DX® Genomic Prostate Score (developed with assistance by Dr. Klein and colleagues at Cleveland Clinic) also may provide physicians with a tool to help decide which men diagnosed with prostate cancer require curative treatment or can be safely monitored with active surveillance.

The Genomic Prostate Score checks biopsy specimens for biologic characteristics associated with aggressive prostate cancer and can predict the likelihood that a cancer will grow and spread. Likewise, two others tests, Prolaris® and Promark ®, combine traditional risk factors with genetic testing of biopsy samples to estimate a cancer's aggressiveness.

Active surveillance is now recognized as a viable management strategy for low-risk and some intermediate-risk prostate cancers. Yet, some men on surveillance still develop metastatic prostate cancer or die from the disease.

“What that tells you is there's a real need for these tests,” Dr. Klein says. “The paradigm is set now. Many physicians understand that active surveillance is appropriate for many patients, but they still don't have confidence about how to pick the correct patients. The idea that these tests can help fill that void is gaining wide traction now.”

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