What to Do When Prostate Cancer Biopsy PSA Test Results Conflict.

Prostate cancer can be challenging to detect. Our screening and diagnostic tools—prostate-specific antigen (PSA) testing and transrectal ultrasound-guided (TRUS) prostate biopsy—aren’t perfect. And it becomes even more difficult when those tools contradict each other.

Finding high levels of PSA, a protein made in the prostate gland, in a man’s bloodstream can indicate prostate cancer. However, PSA testing has a 15 percent false-positive rate, which means the test may detect cancer that isn’t present.

And a high PSA level usually leads to a biopsy. A TRUS prostate biopsy samples less than 1 percent of the prostate, and the false-negative rate can approach 35 percent, meaning it shows no cancer even though cancer is present.

Learn more: Should men get a PSA test to screen for prostate cancer, and when?

So what are a man and his doctor to do when his PSA level indicates he has prostate cancer but his biopsy says he doesn’t?

Your doctor may suggest doing another traditional biopsy, but because it takes random samples, it can be like trying to find a needle in a haystack. Your biopsy also may find a low-grade cancer, which means the abnormal cells are unlikely to impact your life and may only need close monitoring, not treatment. Also, there are risks associated with repeat biopsies, including bleeding and infection.

When we encounter cases like these, we turn to two advanced options to guide our decision to do a repeat biopsy: MP-MRI or checking biomarkers. These options can:

• Rule out clinically significant prostate cancer, which can reduce your anxiety and potentially avoid a repeat biopsy.
• Indicate you may be harboring undetected cancer, which may prompt another biopsy and, potentially, treatment.

Using MP-MRI to target prostate cancer

Multi-parametric magnetic resonance imaging (MP-MRI) has emerged over the years as an imaging test that can improve the accuracy of detecting aggressive prostate cancer.

MP-MRI uses the same machine as other MRI imaging but differs in that it uses multiple, specific imaging sequences instead of just one. If a patient has an elevated PSA level but a negative biopsy, we can use MP-MRI to detect suspicious lesions. If such lesions are found, we can target them with a biopsy using a unique platform that fuses the previously obtained MRI images with real-time ultrasound in our clinic.

When an MP-MRI shows no suspicious lesions, the results are 89 percent accurate. And in men with a prior negative biopsy, up to 87 percent of tumors detected by MP-MRI are considered “clinically significant,” which means there is a tendency for these tumors to grow and potentially become metastatic.

While we regularly use MP-MRI for repeat biopsies, it’s also being studied as a first line of testing for prostate cancer. We might be able to avoid the potential negative effects of PSA testing and biopsy by screening at-risk men with MP-MRI instead. Until we have more data on that use, we’re glad to offer MP-MRI to men whose other test results are inconclusive.

Using biomarkers to guide our next step

While MP-MRI has proven to be an effective tool in diagnosing prostate cancer, not every facility has the technology needed to perform it—the MRI machine and special biopsy platform—or radiologists with the expertise to read a prostate MRI. In addition, the test can take up to an hour in an MRI machine, which can be uncomfortable for patients, particularly if he is claustrophobic.

In these cases, biomarkers can be useful to potentially avoid repeat biopsy. Biomarkers indicate whether a certain body process is normal or abnormal. These biomarkers can pinpoint men who actually need a repeat biopsy, as well as help us find more aggressive cancers.

Types of biomarkers we can use to detect prostate cancer include:

• Urine-based: This test looks for prostate cancer gene 3, or PCA 3. These genes make prostate cells produce a particular protein, and prostate cancer cells make more of this protein than normal cells. There are two parts to this test. First, you doctor will do a rectal exam to massage the prostate gland. This helps move the PCA3 into the urine. Then, you’ll give a urine sample. The reading will give an indication of your risk of prostate cancer. A higher PCA3 score also can indicate a higher-grade cancer.
• Blood-based: Tests, such as the Prostate Health Index (PHI) or 4K score, are based on PSA testing but are more sensitive than PSA alone. They combine multiple biomarkers, including total PSA, free PSA, proPSA and human kallikrein-2, to come up with a score that can tell what your risk of prostate cancer might be.
• Genomic: Noncancerous prostate tissue located near a tumor will show a “cancerization” process at the DNA level. The ConfirmMDx text looks for that process in a sample from the first biopsy in which cancer was not detected. This can indicate whether that sample is near cancerous tissue. These tests have been shown in clinical practice to decrease repeat-biopsy rates from 43 percent to 4.4 percent, helping men avoid unnecessary biopsies.

If a biomarker test suggests that the initial biopsy failed to diagnose prostate cancer, a repeat biopsy is recommended. Ideally, you would get an MP-MRI, but if you don’t have access to that technology, you may get a traditional prostate biopsy. However, if a traditional biopsy still doesn’t find high-grade prostate cancer despite biomarkers indicating it, you may want to travel to the nearest facility with MP-MRI.

A high PSA level and negative biopsy can certainly cause you and your doctor to feel nervous. But MP-MRI and biomarkers can provide reassurance that our next step is the right one.