Alternatives to Random 12-Core Biopsy of the Prostate

Senior patient about to receive an MRI scan

Every year 15,000 urologists from around the world attend the annual American Urology Association (AUA) meeting to present their latest findings from ongoing medical research and share the most recent breakthroughs in prostate cancer management. The May 2017 event revealed progress in pursing alternatives to the 12-core random needle biopsy of the prostate. Here, we'll discuss two of these new alternatives—the OPKO 4k blood test and the 3T multiparametric MRI (MP-MRI).

Both effectively lower the need for using a 12-core random biopsy.

More than one million men undergo the 12-core random biopsy every year. This procedure leads to serious infections, impotence, and other complications. Worst of all, it results in the unnecessary diagnosis of Grade 6 prostate cancer for more than 100,000 men annually; over the last 10 years, experts have learned that Grade 6 should never have been considered cancer in the first place, as it has no metastatic potential. Nevertheless, after being diagnosed with Grade 6—almost always as the result of a 12-core random biopsy—upwards of 50,000 men annually undergo radical surgery or radiation to treat this essentially harmless condition. It’s easy to see why alternatives to the 12-core biopsy are beneficial and exciting.

Benefits of a Simple Blood Test

In a presentation at the 2017 AUA, Dr. Stephen Freedland from Cedars Sinai in Los Angeles discussed the ability of the OPKO 4K blood test to predict clinically significant prostate cancer (CSC).

This is defined as Gleason 7 or higher prostate cancer, the type of prostate cancer that needs to be treated. He and his co-investigators compared the OPKO test to a standard PSA algorithm enhanced by other important predictive factors such as the patient’s age and digital rectal exam.

The trial involved 366 men and the OPKO test was demonstrated to achieve a statistically significant improvement in accuracy over the PSA algorithm for predicting CSC.

The test was also found to be accurate in African American men (a population with the world’s highest incidence of prostate cancer). Since it is a simple blood test, OPKO is the logical first step for the evaluation of undiagnosed men with PSA levels above the normal range for their age.

Advancements in Prostate Imaging

Historically, prostate scans were terribly inaccurate. Even now, scanning is so new that prostate cancer diagnosis still relies heavily on the 12-core random biopsy. This is why imaging is one of the hottest and most rapidly developing areas of prostate cancer research.

There are several revolutionary aspects to imaging with multiparametric MRI (MP-MRI):

  1. MP-MRI, rather than random biopsy, can be the first diagnostic step. A scan preformed at a center of excellence is much more accurate than a random biopsy for detecting clinically significant prostate cancer.
  2. If the scan detects an abnormality, needle biopsies can be directed straight at the potential tumor using a limited number of targeted biopsies. If cancer is present, the information about the Gleason grade is more accurate.
  3. Determination of the cancer’s stage is far more accurate. For example, cancer invasion of the seminal vesicle (outside the gland) is much easier to detect by MP-MRI than with a random biopsy.
  1. Men with low-grade cancer, who have decided to monitor their situation with active surveillance, have the alternative of using MP-MRI rather than doing 12-core random biopsies on a regular and ongoing basis.

One of the most important breakthroughs in the field of prostate imaging has been the development of a uniform system to quantify abnormal spots (otherwise known as “lesions”). The most popular, Prostate Imaging Reporting and Data System (PI-RADS), grades lesions on a one-to-five scale. Patients should realize that this system is new, and the doctors who read these scans are still learning how to use PI-RADS to its greatest advantage.

Doctors Peter Pinto and Peter Choyke from the National Cancer Institute reported on the accuracy of PI-RADS for detecting clinically significant prostate cancer (CSC), which again, was defined as Gleason 7 or higher. They evaluated 339 patients who underwent an MP-MRI. Abnormal lesions were further evaluated by doing a targeted biopsy. When PI-RADS level 5 lesions were biopsied, CSC was diagnosed 72 percent of the time. However, only 22 percent of PI-RADS 4 lesions, 12 percent of PI-RADS 3 lesions and 10 percent of PI-RADS 2 lesions showed CSC.

Based on this information obtained from a leading center of excellence, it seems logical to consider performing a targeted biopsy for men who have PI-RADS 4 and 5 lesions and simply monitoring men by repeating the MP-MRI in 6 to 12 months if a PI-RADS 1, 2, or 3 lesion is detected.

How Accurate Are These Scans?

According to additional research into the PI-RADS system for reading MP-MRI, authored by Dr. Gerald Andriole and others, the correct assignment of PI-RADS score by trained radiologists requires innate talent, not just experience. Accurate results are not dependent simply on long experience with reading scans. In this study, researchers looked at the accuracy of the PI-RADS readout from four radiologists of varying experience and found that accuracy was not improved by greater experience.

In this study, a targeted biopsy was used to measure the accuracy when the radiologist assigned a PI-RADS level 4 or 5 lesion, whether the biopsy showed a Gleason score of 7 or above. In the study, the images for these patients were de-identified and then loaded by a blinded third party. The radiologists, therefore, interpreted all prostate MRIs independently. A “mistaken” read was defined as the assignment of PI-RADS 4 or 5 with a follow-up biopsy that showed either Gleason 6, or no cancer whatsoever. Another “mistaken” read was the assignment of PI-RADS 1, 2 or 3 when the biopsy result was Gleason 7 or above.

The accuracy of the doctor’s readouts ranged from 56 percent to 75 percent and more accurate findings did not correlate with the length of the physician’s experience reading MP-MRI. So, what does this mean to a patient? It turned out that a compilation of interpretations from all four radiologists gave the most accurate results. This suggests that consensus interpretation of prostate MRI may be a way to improve predictive accuracy.

What Impact Do Testosterone Levels Have on Scans?

Now that MP-MRI is increasing in popularity, another important question has arisen, “How do low testosterone levels impact the accuracy of MP-MRI scans?” This is a critical issue. As men get older, their testosterone levels frequently decline. Since lowering testosterone is well known to have an anticancer effect, how might these low testosterone levels affect MP-MRI?

Another study, also originating from the National Cancer Institute, analyzed 522 hypogonadal patients. Their median PSA was 6.66 and median testosterone was 171. These 522 men were compared with another, much larger group of men whose median testosterone was 311. It turns out that the imaging results between the two groups were similar, though there was a somewhat lower detection rate of clinically significant cancer in the hypogonadal men (28.8 percent vs. 37 percent). However, the detection rates when a targeted biopsy was performed were similar (40.4 percent vs. 43.6 percent).

Of the 522 men, 78 went on to be treated with surgery. The final pathology reports in these 78 patients, (compared to another group of surgically treated men with normal testosterone), showed a higher rate of Gleason score upgrading (22.2 percent vs. 12.5 percent), more frequent seminal vesical invasion (11.1 percent vs 6.0 percent) and more frequent lymph node invasion (11.1 percent vs 7.5 percent). Based on these study results, low testosterone levels should cause doctors to be a little warier of favorable findings reported on MP-MRI.

Another study from the University of California, San Francisco evaluated how well PI-RADS predicts the pathology findings after surgery (presumably in men with normal testosterone). In this study of 121 patients, the researchers looked at how well PI-RADS predicted the occurrence of either a high Gleason score (4 + 3 = 7 or higher) or spread of cancer outside the capsule of the prostate gland. The MP-MRI prior to surgery indicated that 69 of the 73 patients with adverse pathology had either PI-RADS 4 or 5. While the authors concluded that a PI-RADS score of 4 or 5 is highly sensitive for the detection and prediction of adverse pathology, PI-RADS 4 or 5 over-predicts adverse pathology to some degree. For example, of all the men with PI-RADS 4 or 5 prior to surgery, only two-thirds were found to have adverse pathology.

MP-MRI also offers a significant advantage over the 12-core random biopsy for men on active surveillance—an increasingly preferred way to manage Grade 6 prostate cancer. Modern research has concluded that Grade 6 has no metastatic potential. In other words, it can’t spread and it’s not really a cancer. Active surveillance enables men to safely postpone surgery or radiation for many years.

Active Surveillance and Grade 6 Prostate Cancer

If it’s true that men on active surveillance observation shouldn’t be concerned about Grade 6, the real concern is the possibility of harboring Grade 7 or higher cancer that was missed by the initial random biopsy. Studies show that random biopsy misses higher-grade disease 25 percent of the time. The study from UCSF, cited above, reported that MP-MRI detects Gleason 4 + 3 = 7 or higher 95 percent of the time. Clearly, this study supports the premise that men with Gleason 6 who are contemplating active surveillance should undergo an MP-MRI to make sure there is no CSC that was missed by the random biopsy.

In another study, a group of doctors based in Ann Arbor, Michigan also looked at the issue of doing MP-MRI in men pursuing active surveillance. They did a retrospective review of 225 men, 209 with Gleason 3+3=6 and 16 with Gleason 3+4=7. All underwent MP-MRI followed by a targeted biopsy if there was a suspicious lesion. Results indicated that without undergoing an MP-MRI, 12 patients with higher grade disease would have been missed and would have inappropriately been placed on active surveillance. Targeted biopsy showed Gleason score upgrading to Gleason 4+3=7 in two patients, to Gleason 4+4=8 in 9 patients and to Gleason 4+5=9 in one patient.

A Word From Verywell

The 12-core random biopsy, first developed in the late 1980s, was, at one time, the only way to diagnose early-stage prostate cancer. However, we now know that each year more than 100,000 men who have harmless grade 6 disease are diagnosed by means of random biopsy. This diagnosis leads to unnecessary treatment in 50,000 men annually. Until we learn how to defuse the scary terminology associated with Grade 6, the best protection is to avoid the random 12-core needle biopsy altogether. Men with high PSA levels should consider doing an OPKO 4K blood test. If the test results indicate that the risk of high-grade disease is over 10 percent, a MP-MRI at a center of excellence would be the next logical step.


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