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.

If you’re considering your next step after a high PSA result and negative biopsy, or you want to know what type of prostate cancer screening you may need, request an appointment with one of our doctors.

How Doctors are Screening Smarter for Prostate Cancer

Washington, D.C., September 27, 2017 - The prostate-specific antigen (PSA) test is one of the best screening tools for prostate cancer. While there’s no doubt this simple blood test has saved lives over the years, it’s not perfect. There’s been a lot of debate over who should be screened and when—and whether men should be screened at all.

Since the PSA test became widely available in the late 1980s, deaths related to prostate cancer began to decrease. In fact, mortality rates fell nearly 40 percent between the early 1990s and 2008. However, there also have been some negatives associated with the test, the biggest being its 15 percent false-positive rate. This means 15 in 100 men who get an elevated PSA test result do not actually have prostate cancer.

PSA testing also can increase the risk of overtreatment. Most diagnosed prostate cancers are low-grade, which means the abnormal cells are unlikely to impact a man’s life in any way. Prostate cancer is a slow-growing cancer, taking 10 to 15 years to progress and even longer to cause death. These tumors may only need close monitoring over the years, also known as active surveillance, and not treatment.

“PSA testing is not a one-size-fits-all approach to prostate cancer screening,” said Ross Krasnow, MD, a urologic oncologist at MedStar Washington Hospital Center. “The key is to have an honest conversation about the potential benefits and harms for each man based on his specific risk factors.”

For a man at average risk for prostate cancer, the discussion may center more on the potential benefits and harms of a PSA test. However, the conversation may take on a more urgent tone if the man has factors that put him at increased risk for prostate cancer. These can include:

  • Family history: Having a first-degree relative, such as a father or brother, who had the disease.
  • Genetic mutations: Continually learning more about how certain gene mutations can increase a man’s risk for prostate cancer. This includes mutations of the BRCA1 and BRCA2 genes, which are more commonly associated with breast and ovarian cancers.
  • Race: African-Americans have double the incidence of prostate cancer compared with white men, and their risk of dying from the disease is two to three times higher.

A man’s age also should be taken into effect. “Because prostate cancer grows so slowly, there’s little benefit to screening older men whose life expectancies are less than 10 to 15 years,” said Dr. Krasnow. “When I see a patient who is 70 or older and has been referred to me for a PSA test, I usually advise against it unless they are extremely healthy for their age.”

Prostate cancer is the most common cancer in men, with one in seven men in the United States projected to get the disease in their lifetime. And the District of Columbia has the second highest prostate cancer incidence rate in the country behind only Louisiana, with 123 out of 100,000 men diagnosed with the disease in a given year.

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

Prostate cancer is the most common cancer in men, with one in seven men in the United States projected to get the disease in their lifetime. And the District of Columbia has the second highest prostate cancer incidence rate in the country behind only Louisiana, with 123 out of 100,000 men diagnosed with the disease in a given year.

One of the best screening tools we have for this disease is the prostate-specific antigen (PSA) test. While there’s no doubt this simple blood test has saved lives over the years, it’s not perfect. There’s been a lot of debate over who should be screened and when—and whether men should be screened at all. Even national health organizations differ slightly on their PSA testing guidelines.

PSA testing is not a one-size-fits-all approach to prostate cancer screening. The key is to have an honest conversation about the potential benefits and harms for each man based on his specific risk factors.

Tune in to this podcast to hear Dr. Krasnow further discuss PSA testing, including what men may expect from future prostate cancer screening.

Benefits and risks of PSA testing

Prostate-specific antigen is a protein made in the prostate gland and present in semen. A small amount of PSA enters the bloodstream, but high levels in a man’s blood can indicate prostate cancer. After the PSA test’s introduction in the late 1980s, deaths related to prostate cancer began to decrease. In fact, mortality rates fell nearly 40 percent between the early 1990s and 2008.  

This was a huge win in our fight against prostate cancer. However, there also have been some negatives associated with the test, the biggest being its 15 percent false-positive rate. A false positive is when the test detects cancer that is not present.

This means 15 in 100 men who get an elevated PSA test result do not actually have prostate cancer. Unfortunately, to confirm this, they’ve likely undergone an unnecessary biopsy. While generally safe, biopsies can cause complications, such as bleeding or infection and can induce unnecessary stress for the patient.  

PSA testing also can increase the risk of overtreatment. Most diagnosed prostate cancers are low-grade, which means the abnormal cells are unlikely to impact a man’s life in any way. Prostate cancer is a slow-growing cancer, taking 10 to 15 years to progress and even longer to cause death. These tumors may only need close monitoring over the years, also known as active surveillance, and not treatment.

Do the potential benefits of PSA testing outweigh the potential harms? It depends on the person. Some of my patients who have received a false positive were relieved to know their cancer status for sure. Others, while relieved, continued to worry about their elevated PSA level as we monitored them over the following years. And still others were frustrated that they had to go through the biopsy process, which, while not painful, is awkward and uncomfortable.  

What studies and guidelines say about PSA testing

Actor Ben Stiller made waves in 2016 with a blog post titled “The Prostate Cancer Test That Saved My Life.” In the article, he attributed surviving prostate cancer to having a PSA test at age 46—earlier than most guidelines would recommend—despite having no indicators that he was at increased risk for the disease.  

He wrote: “If (my doctor) had waited (to get me a PSA test), as the American Cancer Society recommends, until I was 50, I would not have known I had a growing tumor until two years after I got treated. If he had followed the U.S. Preventive Services Task Force guidelines, I would have never gotten tested at all, and not have known I had cancer until it was way too late to treat successfully.”

If you’re looking to various health organizations for guidance on when you should have a PSA test, you may be confused by the differing recommendations. And these recommendations also may change over time. For example, the U.S. Preventive Services Task Force slightly revised its guidelines since Ben Stiller had his PSA test based on new evidence and studies.

Here is what some health organizations currently recommend:

  • American Cancer Society: The organization recommends that men at average risk for prostate cancer begin discussing screening with their doctors at age 50. Men at increased risk should consider screening at age 45.
  • American Urological Association: The organization recommends that doctors begin discussing screening at age 40 to 54 for men at high risk, 55 to 69 for men at average risk, and 70 and older for some men in excellent health with a 10- to 15-year life expectancy.
  • U.S. Preventive Services Task Force: The group in 2017 recommended that while the PSA test should not be used routinely, physicians should discuss the benefits and harms with men age 55 to 69. It recommends against PSA screening for men 70 and older. This is in contrast to its 2012 guidelines that recommended against PSA screening in men without prostate cancer symptoms.  

So what’s a man supposed to do? The answer lies in the common theme to these recommendations: a discussion between doctor and patient.  

How I advise men about screening for prostate cancer

I once treated a man in his 40s who was exhibiting signs of benign prostatic hyperplasia, a condition in which the prostate is enlarged. We decided to do a PSA test, despite most guidelines recommending against PSA testing for a man younger than 50 with no increased risk factors for prostate cancer. The test showed elevated PSA levels, but a traditional biopsy only found very low-grade cancer.  

This didn’t make sense considering his high PSA levels. We had a long conversation about how to proceed, and we decided to do advanced testing. An MRI-guided biopsy that is increasingly being used to detect prostate cancer revealed a high-grade prostate cancer that, left unchecked, would have been lethal.  

PSA test guidelines aren’t hard and fast rules—as my patient and Ben Stiller would attest to. The key is an open, honest conversation in which the patient and doctor come to a decision together.

Related reading: Shared decision-making: It’s no longer “doctor knows best”

For a man at average risk for prostate cancer, the discussion may center more on the potential benefits and harms of a PSA test. However, the conversation may take on a more urgent tone if the man has factors that put him at increased risk for prostate cancer. These can include:

  • Family history: Having a first-degree relative, such as a father or brother, who had the disease.
  • Genetic mutations: We’re continually learning more about how certain gene mutations can increase a man’s risk for prostate cancer. This includes mutations of the BRCA1 and BRCA2 genes, which are more commonly associated with breast and ovarian cancers.  
  • Race: African-Americans have double the incidence of prostate cancer compared with white men, and their risk of dying from the disease is two to three times higher.

A man’s age also should be taken into effect. Because prostate cancer grows so slowly, there’s little benefit to screening older men whose life expectancies are less than 10 to 15 years. When I see a patient who is 70 or older and has been referred to me for a PSA test, I usually advise against it unless they are extremely healthy for their age.  

I think as medical professionals, we’re doing a better job of screening smarter and being more selective in who gets a PSA test. But discussion is the key.

Request an appointment to talk to a doctor about your prostate cancer risk and screening options.