A Clinical Perspective
There are over 150,000 prostate cancer articles and abstracts published each year. Trying to select which are the most important is impossible. These are just a few new developments that are changing the way that prostate cancer is diagnosed and managed.
A new genetic test has been developed that can predict the most aggressive types of prostate cancer. A prostate biopsy pathology report is assigned a Gleason grade of 3, 4 or 5 by the pathologist (2 grades are added to create the Gleason Score.) Grade 3 (Score 6) cancer cells are considered to be the slow growing variety and these men are often assigned to a program of Active Surveillance. But as many as 30% of these men will be found to actually have more aggressive disease and require therapy at a later time . The ability to understand the behavior of these grade 3 tumors would separate those who really have a more aggressive tumor from those that do not. The OncotypeDx Genomic Prostate score uses a panel of 17 genes that have been associated with prostate cancer gives us that ability.
In one study, biopsy samples were analyzed in a group of 400 men who subsequently had prostate surgery and initially, they were all thought to be of low risk for cancer recurrence. Dr. Peter Carroll and his associates found that the risk category was changed in 23%.  The implication is that not all grade 3 or even some grade 4 tumors may not behave as expected. A test to clarify the potential aggressiveness of these cancers can spare more men from unnecessary treatment and treat those who would derive the most benefit from treatment. The test results are likely to be helpful in half of the patients and highly significant in a quarter of the patients who participated in this study.
The use of MRI in prostate cancer management is being done with increasing frequency. The specific name for this is a multiparametric-MRI, or mp-MRI. This imaging study used to be done with a probe in the rectum (endorectal coil) and after 45 minutes of experiencing the probe and the loud pounding of the machine, most men did not want to return. Now, the probe is not usually necessary but the pounding noise remains.
Mp-MRI allows us to see abnormalities in the prostate that are suspicious for aggressive prostate cancer. The test does not detect every small, aggressive tumor. It tends to miss cancers that are considered to be insignificant or low grade, which actually is a good thing. No test is perfect but in experienced hands, the ability to detect Gleason score 7 and 8 tumors was accurate in 98% and the ability to predict the absence of aggressive tumors was 91%.  Pretty good!
The radiologist reading the MRI images of the prostate assigns a score on a 5 point scale to express the probability of high grade, aggressive cancer being present. If the score is 5/5, the possibility of an aggressive tumor is > 90%. If the score is 1/5 the probability of there being a high grade cancer is less than 10%. If there is a 4/5 abnormality the positive biopsy result for an aggressive tumor is > 75%. A 2/5 is associated with a low probability of there being an aggressive cancer and a 3/5 means that we don’t know what’s going on.
Here is how this information is being used. When a man visits a urologist because of an elevated or rapidly rising PSA, an mp-MRI can not only help determine the probability of an aggressive cancer but also where it is located within the prostate. This allows a more targeted approach to doing a needle biopsy. If the radiologist reports a 4/5 or a 5/5, a targeted biopsy is advised. A 1/5 or a 2/5 is usually adequate evidence that a biopsy is not necessary. A 3/5 means that you have to decide for yourself whether or not to have a biopsy based upon other factors. New biopsy techniques permit a prostate biopsy to be done at the same time that the mp-MRI is performed. Another method is to overlay the images on ultrasound in order to biopsy the most relevant areas. The mp-MRI is also very useful for following patients with prostate cancer who are on Active Surveillance. The number of follow-up biopsies can be reduced which makes everyone happier. Mp-MRI is also being used to assess the nerve bundles and any unusual anatomic features prior to surgery.
Here’s the problem. It takes the right kind of MRI, not all MRI’s are the same. Most experts argue that a 3-Tesla MRI is needed. Most important, a highly trained and experienced radiologist is critical to perform and interpret the study and there aren’t that many of them. There is also the issue of cost. This is an expensive test that is not always covered by insurance. Undoubtedly, the mp-MRI has an important role in the diagnosis and management of prostate cancer, but how it will be integrated into clinical practice will need further study.
Medications to treat osteoporosis in men who are receiving “hormone therapy” have been used for years. But now we have learned that men who have bone metastases can have a stabilization and regression of the tumor with the use of these agents. Denosumab, also known as Prolia and XGEVA, are being used with good results. In fact, in a recent publication, Dr. Matthew Smith and his colleagues reported that the use of Denosumab can be a preventive agent and delay the onset of bone metastases in patients who are at high risk.
Another agent that has recently been approved by the FDA called Xofigo is used to treat existing bone metastases in men who are having pain . Xofigo consists of radium that is injected into the bloodstream. The radioactive radium has a special affinity for metastatic spots in the bone so when it localizes near the cancer it ends up delivering a high dose of radiation directly to the cancer. Xofigo is available at various sites throughout the country. There is low toxicity but high effectiveness.
The plan going forward for this column is to continue providing quarterly updates of the recent developments in scientific literature in future issues of Insights. In the next issue, we’ll enter the confusing world of “Alice in Dietland.” We’ll see if we can make some sense of the many confusing articles that have been published about the role of diet and prostate cancer.
Helpful links for further research: