Three reasons why prostate cancer genomic testing is flawed
Commentary by Dr. Claus Roehrborn
When it comes to helping a patient choose between prostate cancer treatment and active surveillance, there’s rarely a 100 percent definitive answer. Many men and their partners want us to look into the future and tell them how the cancer might affect their life and their survival. Believe me – if we could, we would. While we don’t have a crystal ball at our disposal, genomic testing can be an additional help to guide patients with data. However, like any other test, there are some aspects of it that I’m not convinced are always in most patients’ best interest.
Genomic testing compares a protein expression profile in randomly biopsied samples of a patient’s prostate tumor to those of hundreds of men with known outcomes and determines the closest genetic match. This is how the patient is told that his cancer might behave in a very similar way. The comparison usually results in some number or percentage. For example:
- “In the next 10 years, your risk for developing advanced prostate cancer is 3 percent.”
- “The risk of you having aggressive cancer is 13 percent.”
- “The risk of you dying from this cancer in the next 10 years is 3.5 percent.”
We can use this number in our recommendation for patients to pursue active surveillance, radiation, or surgery. But while genomic testing can be helpful in combination with thorough conversations and additional health considerations, many urologists and patients may incorrectly assume it to be a 100 percent correct prediction tool – an opinion several experts expressed in an April 2018 article in The Wall Street Journal.
Selecting a prostate cancer treatment shouldn’t come down to one data point from one imperfect test. It’s vital for doctors to help patients understand exactly what the data mean and how the test results factor into the overall risk.
Three reasons why prostate cancer genomic testing is flawed
1. Sampling issues
Genomic testing is touted as a predictor for the future behavior of a tumor. However, the sample area usually is selected by random and might not represent the most advanced or aggressive area of the cancer in the prostate gland. If the patient is lucky enough to have the most severe portion of the cancer biopsied, he will have a more solid answer. Unfortunately, there is no way to tell whether that is the case.
For example, if a patient’s prostate is 50 grams, and the doctor takes 12 biopsies, we’ve sampled less than 0.1 percent of the prostate. Such a limited sample area means it’s likely to miss areas of the patient’s cancer or even additional cancers with different genetic makeups. The limits of the genomic tests mean we can estimate risk only for the cancerous tissue that is biopsied.
Most academic medical centers, such as UT Southwestern, typically perform high-resolution magnetic resonance imaging, or MRI, before a biopsy to determine which area of the prostate is at highest risk for cancer and therefore should be biopsied. This protocol can help some patients avoid biopsy altogether, and for those who have a biopsy, it helps us target the selection to the most advanced portion of the tumor, potentially leading to a more accurate result and more accurate testing.
2. Abstract data
Even if a biopsy is well-targeted, we have to keep in mind that the number is only one factor to consider when discussing treatment options. Patients expect to receive an answer they can follow. However, the tests often provide a range of uncertainty instead, and the report does not always convey that sense of uncertainty around what is known as the point estimate. For example, “Your risk of dying from this cancer in the next 10 years is 3.5 percent, but the range of uncertainty may be from 0.5 to 15 percent.”
Furthermore, even the best test can only provide a snapshot of what the cancer might look like today, but:
- A cancer that appears low-risk on today’s biopsy might turn more aggressive in a year or two and require treatment.
- Conversely, the test might suggest a cancer is high-risk, but the tumor might never get worse or require treatment.
I see my patients every six months. Will a prostate cancer advance so quickly that a patient could die in six months? It’s highly unlikely. But the patient’s situation can change enough in that time that he needs to discuss different treatment options. The reality is that prostate cancer genomic testing is more a gauge of what's happening right now than a glimpse into the future,
3. Life is a continuum
The data from prostate cancer genomic testing are meant to suggest a patient's risk over the next 10 years – but the human mind is not wired to think about life like that. Life is a continuum with moving parts, not a straight line that can be cleanly divided into neat time segments in which everything or nothing could happen.
Different genomic tests usually focus on different outcomes, such as survival, developing cancer spread, needing radiation or more treatment, having a recurrence, etc. All these tests cost substantial money, and rarely will a single patient have access to all the tests to have as complete a picture as possible. This could lead to biases in decision-making as per the example below.
For example, imagine you need to buy a new refrigerator. You’ll likely look at various models with different benefits and warranties. Say you find one you like, but the salesperson says that the risk that the icemaker will break in 10 years is 5 to 9 percent. You might decide that's too much risk and choose a different model. But what about the risk of the light burning out, or the door not sealing property, or the temperature gauge breaking? You likely didn’t consider those risks because the salesperson gave you only one piece of information.
Similarly, prostate cancer genomic testing doesn’t account for factors outside the tumor itself, such as a patient’s risk for chronic diseases, smoking, or other risk factors, but all these are important to consider when choosing a treatment option. We must ensure the patient understands the number reflects not his risk of dying, but, rather, the risk that his cancer might spread. Life is not so black and white as to say, “This test definitely means you need surgery (or radiation or active surveillance).”
Other factors to consider when selecting treatment
No single test can return a recipe for what a patient should do. Every treatment plan must come down to a patient’s unique condition, needs, home life, professional life, and goals. The first data the doctor must gather should focus on whether the cancer is a threat right now, or whether the patient can avoid risks associated with treatment by undergoing active surveillance.
Then we must ask patients and their partners a series of questions to agree upon a treatment plan together:
- Do the symptoms affect your quality of life?
- Are you at risk for other conditions that could make the symptoms less tolerable?
- Do you want to undergo genomic testing?
- If the result is negative, do you want an MRI and a biopsy?
- Do you live close enough to the hospital to get radiation therapy for five weeks, or are you willing to travel for treatment?
More than 160,000 new cases of prostate cancer are diagnosed every year in the U.S. Many men can be monitored over time without immediate treatment because their cancers are small, low-risk, and not causing intolerable symptoms. Others have more advanced cancers that require treatment right away. However, many cases fall in the gray area where the decision is not as conclusive. Genomic testing can play an important role in these situations if doctors and patients have a thorough understanding of what the results mean.
Ultimately, treatment or surveillance is the patient’s decision, but doctors need to treat not only the cancer but the patient as well. We must look at the patient’s age, health history, and lifestyle along with the data to help make educated decisions about his care.