Prostate cancer treatment needs to get more personalized

As a group, men who choose not to treat their early-stage prostate cancer aren’t any more likely to die from the disease within 10 years as men who choose treatment with surgery or radiation, which often come with potentially life-changing side effects. That’s the main finding of a landmark trial published recently in the New England Journal of Medicine.

While important, this finding cloaks the reality that active surveillance — forgoing immediate treatment but regularly monitoring the cancer — isn’t a good option for all men. The study highlights the need for further research into an area that is showing great promise: personalized medicine, which uses tools like genetic testing to help more accurately pinpoint the aggressiveness of a man’s prostate cancer and better match a particular man and his cancer to the right treatment option.

The results of the long-awaited ProtecT clinical trial reinforced a growing belief that treating early-state prostate cancer with surgery or radiation therapy may be no more life-saving than monitoring it. There’s more to the story, of course.

It’s important to keep in mind that the men in the trial had very low-risk prostate cancer. That means when their cancer was diagnosed, it was confined to the prostate gland and the cancer cells were low-grade, or likely to grow and spread very slowly. So it wasn’t a surprise there were no differences in survival across the surgery, radiation therapy, and active surveillance groups. Yet even with such non-aggressive cancer, more men in the active surveillance group saw their cancer spread outside the prostate to their lymph nodes and bones within the 10-year study period. For them, the road ahead is likely to be tougher than it would have been if they had undergone treatment with surgery or radiation earlier. They’ll likely require aggressive interventions in the years to come, such as hormonal treatments and chemotherapy, and their chances of very long-term survival, well beyond the decade that the research took place, may be bleaker.

Although it’s important to push back against over-treatment for cancers that will never become life-threatening, physicians also must be able to make informed decisions about who can afford to wait and who should be treated quickly. While we can’t easily answer that question today, research underway in my health system and others is closing in on one.

With personalized medicine, we’re already seeing how these tools can be used to help men make more informed decisions about their disease and to customize treatments for them.

In my clinical practice, I recently saw a man with early-stage prostate cancer who had opted for active surveillance. I learned during the visit that some of his family members had developed prostate, breast, or pancreatic cancer. I recommended that he have a genetic test to get a better sense of his risk factors. It showed that he was carrying the BRCA genetic mutation. While well-known for its association with breast cancer, this gene variation is also common in men who develop aggressive, deadly prostate cancer.

Although a biopsy sample of his cancer showed that this patient was a good candidate for active surveillance, the BRCA mutation made it clear he was at higher risk than the average man with early-stage disease. He had surgery, and is currently doing well with no side effects. A pathology report of his entire prostate gland found that his cancer was significantly more aggressive than the biopsy had shown, confirming the decision to remove his prostate and potentially preventing the development of aggressive, life-threatening cancer.

The information we’re able to glean with tests for mutations like BRCA offers a good start, but it is just the beginning. Many genetic factors we can’t yet measure affect an individual’s chance of developing aggressive cancer. Several large studies currently underway seek to better understand the cancer risk associated with genes that are passed through generations.

At NorthShore University HealthSystem, for example, we are leveraging unique risk assessment methods to investigate genetic variations in men with prostate cancer who responded well to treatment compared to men who died from the disease. The goal of the study is to be able to predict the likelihood that a man’s prostate cancer is — or isn’t — an aggressive, potentially fatal type.

We are also working to develop better methods of assessing which patients are most at-risk of developing prostate cancer, which can help physicians decide when individual men should begin to receive screenings such as PSA tests. From this research has emerged a highly validated genetic risk score that provides personalized risk assessment for the development of prostate, breast, and colorectal cancer. We are using this score in combination with other tests such as the Prostate Health Index (a next-generation blood test for hidden prostate cancer) and the 4K score (a blood test to help clarify whether a biopsy is needed after a PSA test) to better understand who is at high risk for developing any form of the disease.

One of the many things we must still learn about prostate cancer is how to tell the difference between prostate cancer that will never threaten a man’s health or well-being and one that, as one of my patients put it, is a “ticking time bomb.” Our work, along with the work of countless other research teams in the United States and beyond, will help point the way toward tests that identify men who are susceptible to developing lethal forms of prostate cancer. This research will also translate to other cancers.

The ProtecT finding that active surveillance works for many men with prostate cancer shouldn’t lead us to believe that it is the right choice for all men with the disease. Prostate cancer is the second leading cause of cancer death in men in the United States, killing more than 25,000 men a year. With the help of ever more effective genetic assessments and other personalized medicine tools, we can reduce the heavy burden of this disease.

Brian Helfand, MD, is a urologic oncologist with NorthShore University HealthSystem’s Center for Personalized Medicine in suburban Chicago.