The PSA and beyond: An update on prostate cancer biomarkers
There is perhaps no hotter topic in prostate cancer treatment today than the use of prostate cancer biomarkers. To learn more about them, we posed a few questions to Todd Morgan, M.D., a surgeon in the U-M Multidisciplinary Urologic Oncology Clinic.
QUESTION: First, Dr. Morgan, can you provide a basic definition of a cancer biomarker?
Dr. Morgan: A biomarker is any type of indicator that can be found in blood, urine or tissue that can be used to identify or predict something – such as when cancer is present, how aggressively a cancer is growing, or how a given tumor will respond to different therapies. Some biomarkers predict only one thing, while some have multiple clinical uses.
Among the most familiar and heavily used cancer biomarkers is the prostate-specific antigen, or PSA, a blood test which came into use in the 1980s in the diagnosis and treatment of prostate cancer. Despite recent controversy surrounding the test, PSA remains the primary predictive tool in prostate cancer.
QUESTION: Can you provide some background into that controversy?
Dr. Morgan: PSA has proven to be an extremely useful marker in patients known to have prostate cancer. After diagnosis, it can help gauge how aggressive the cancer is; after initial treatment, it can reveal whether the cancer has returned; and in patients with advanced disease, it is very useful in determining response to therapy.
The controversy arises when the PSA alone is used to help determine whether healthy men with elevated PSA levels should undergo needle biopsies for the initial diagnosis of prostate cancer. While prostate biopsies are a straightforward procedure, there is some associated discomfort and a small risk of infection. Moreover, only about 40% of biopsies performed for an elevated PSA alone detect any prostate cancer. So we’re anxious to identify new and better predictors to help us avoid unnecessary biopsies.
QUESTION: Can you give us an example of how you’re using other biomarkers to help patients make treatment decisions?
Dr. Morgan: I’ll give you four scenarios we see frequently in our clinic:
Let’s start with the common situation described above – determining whether a man with an elevated PSA level should undergo a prostate needle biopsy. Today, we have four emerging biomarkers that may be helpful for sorting this out. Two are blood tests – the Prostate Health Index (PHI), an FDA-approved test which just became available in the U.S., and the 4K Score, which is still being studied and is likely to receive FDA approval in the next several years. The third, a urine test, measures secretions of the biomarker PCA3. The fourth, the Michigan Prostate Score or MiPS, was developed here at the University of Michigan. MiPS is also a urine test and it measures both PCA3 and another biomarker called TMPRSS2:ERG.
A second example is the patient who has an elevated PSA but has previously had a negative prostate needle biopsy. If the PSA keeps rising, should he undergo another biopsy? Facing the same risks and limitations of the biopsy, we are currently employing many of these same markers to aid in these decisions. In addition, a new test called ConfirmMDX assesses the tissue itself from the original negative biopsy to look for signs of nearby cancer or suspicious cells that might have been missed. Which of these markers is most valuable in this setting still remains to be determined.
A third scenario is the man who has been diagnosed with prostate cancer through a positive needle biopsy. Primary treatment options include prostatectomy (removal of the prostate) or radiation therapy. But if we are able to categorize his cancer as low risk (indolent), then major surgery or radiation might not be warranted. In this case, another option might be active surveillance, which combines regular PSA testing with occasional repeat biopsies in order to identify changes in the cancer if they occur. Distinguishing between indolent and aggressive prostate cancer is a major factor in treatment planning, and we’re optimistic that two new biomarker tests, Prolaris and OncotypeDX, may help us better meet that challenge. Both test tissue from the positive biopsy for abnormal genes that appear to help predict the aggressiveness of the disease.
The last scenario is the patient who has undergone a prostatectomy, and standard pathologic testing on the tumor tissue suggests he might benefit from additional radiation therapy. A new genomic biomarker test called Decipher might be helpful for better quantifying his risk of recurrence, again in the hope that we will be able to administer radiation to only those who need it and are most likely to benefit from it.
QUESTION: What one piece of advice would you give a prostate cancer patient to help him make a wise treatment decision?
Dr. Morgan: Treatment decisions are complex. What these examples don’t highlight is the importance of the patient’s own personal preferences – they are the most important factors to consider and to share with your physician as you work together to determine the best strategy for you. Once you fully understand your options and have arrived at a decision with which you are comfortable, don’t second guess it. Trust yourself.