Risk Stratification Critical to Optimal Prostate Cancer Care

Erik P. Castle, MD

The prostate cancer paradigm continues to evolve with emerging treatment and imaging modalities, but risk stratification is the key to creating an appropriate management strategy—even between very low-risk and low-risk patients, explains Erik P. Castle, MD.

Various factors come into play when deciding whether such patients should undergo active surveillance or active treatment, he adds, including age, biomarkers, and family history.

“It is very important to keep the best interest of the patient at heart,” said Castle. “Take all of the factors into consideration, use that information that we can draw from in a very intelligent way, and educate our patients to give them the best treatment.”

OncLive: Please provide an overview of your presentation.

In an interview during the 2018 OncLive^® State of the Science Summit™ on Genitourinary Cancers, Castle, consultant, Department of Urology, professor of urology, Mayo Clinic, spoke on the importance of risk stratifying low- and intermediate-risk localized prostate cancers.Castle: I spoke about risk stratification for both low- and intermediate-risk prostate cancer, primarily clinically localized cancer. This is the kind that one might be trying to decide whether you’re going to pursue active surveillance or some sort of definitive treatment. You can even sub-stratify low risk into very low-risk and low-risk disease.

Active surveillance rates have increased in recent years. What can be done to further increase these rates?

The talk was an overview of the standard stratification techniques or approaches using different modeling and scores that are out there and available, but it focuses on the evolving use of biomarkers—and even imaging nowadays—when managing patients with newly diagnosed prostate cancer.It’s important to understand that there is a very big difference between very low and low risk. For very low risk, regardless of what the life expectancy is—unless it’s over 20 years—active surveillance is absolutely the preferred and recommended management. While active surveillance is recommended for low-risk disease, that’s also with the nuance of utilizing age, life expectancy, and patient factors to help make that decision. Therefore, we can do a lot more with active surveillance and increase the utilization of it if we do a better job of not only stratifying our patients, but knowing what their expectations are and educating them with what to expect with these low-risk and very low-risk cancers.

Have you ever a treated a patient in that particular scenario?

However, that is not to say that there isn’t a role for treatment, even in low-risk prostate cancer—particularly in a 50-year-old man who has a strong family history for prostate cancer-mortality or has good functional status, and we know that risk in his lifetime is developing significant cancer.Absolutely. For young men with prostate cancer, I usually recommend treatment. The reason I say that is we use different terminology nowadays. We don’t say “prostate cancer screening,” we say, “the early detection of prostate cancer.” This means we are trying to identify patients who truly are at risk of death or suffering from their disease.

What are some staging modalities for patients with high-risk prostate cancer?

One of the biggest risk factors is young age and diagnosis. If a man is diagnosed at a very young age, we know that he is at a significant risk in the span in his life of having issues with the disease—so we tend to treat them more. While active surveillance is still appropriate, what it ends up being is delayed intervention. Therefore, we are trying to preserve a young man's functional status from an erectile function standpoint, but still balance that with the risk of monitoring this cancer. Utilizing these new biomarkers and newly developed imaging studies and approaches are very useful in these patients to help us decide how aggressive we need to be, and when to be aggressive.High-risk prostate cancer, for the most part, is going to be treated unless the patient has a life expectancy that is less than 5 or 10 years. In those patients, there isn’t as much out there besides standard imaging, which would be a CT scan and some sort of bone imaging.

We are now moving away slightly from classic technetium-99 bone scan and using sodium fluoride and PET imaging. There ae some new PET imaging modalities such as PSMA-PET that has yet to be fully FDA approved. Choline C-11 PET scan is available at Mayo Clinic for patients who have been treated for high-risk prostate cancer and have had a biochemical recurrence. Then, there's 18F-Fluciclovine PET/CT.

Clinical trials have looked at adjuvant versus early salvage radiation therapy in early prostate cancer. Do you have a preference?

Utilizing these imaging studies to help better identify patients that are going to benefit from combined therapy with androgen-deprivation therapy (ADT) or a sequence of therapies with radiation, surgery, and ADT is going to be what we will see coming down the pipes here in the next few years.I am more of a fan of observing my patients and giving early salvage therapy. However, there are data that demonstrate a survival benefit in adjuvant radiotherapy in post-prostatectomy patients who have some high-risk features, stage III disease, positive margins, and in some cases positive lymph nodes. There are still data that are yet to be fully analyzed in some trials that are currently ongoing and accruing comparing early salvage to adjuvant therapy.

Why do we say that? We have quite a few patients that we know, from even the original open prostatectomy series where patients were just followed until they were symptomatic, that there are a large percentage of patients who will not recur and not be a risk for dying even though they have high-risk features. We can spare some patients the risks of having this adjuvant therapy. While I absolutely believe that there is a role for adjuvant therapy, especially in patients who are at high risk for recurrence, there are young patients who are clearly going to need trimodal therapy, I tend to advocate monitoring my patients very closely and in a very tight schedule of prostate-specific antigen (PSA) testing and utilizing their time to recurrence, and PSA kinetics to determine how aggressive I’m going to be with radiation.

What recent clinical trials have been impactful in the field of prostate cancer?

We spoke briefly about some tests, particularly the Decipher genomic test that has been utilized in patients to help predict not only prostate cancer-specific mortality, but patients who will benefit from adjuvant therapy in radical prostatectomy cohort.The clinical trials that we tend to talk about the most, and quote frequently, in the world of prostate cancer include the original ADT trial used for patients who had positive lymph nodes at the time of radical prostatectomy, which was the trial [by Edward M. Messing, MD] that demonstrated a survival benefit for early use of ADT. All of the trials that were done not only by [Michel Bolla, MD] and colleagues but the various radiation and RTOG trials that have demonstrated the benefits of using ADT along with hormonal therapy through various different regimens and schedules have shown benefit, as far as patients undergoing RT. Then, of course, the more recent trials that have shown an increasing role of adjuvant therapy in the prostatectomy series are out there.

What are some key things for community oncologists to keep in mind when risk-stratifying their patients?

However, we need to be careful with all of these trials because each patient needs to be treated as an individual. We have to remember that these trials don’t control for individual expectations of patients. There are some other factors that are often very difficult to assess when you’re looking at a cohort of 500 patients. When the patient is sitting in front of you and all of his family members have died of prostate cancer, even if everything suggests it might be low or at best intermediate risk, you might have a different take—compared with an 81-year-old patient who now has a biochemical recurrence and had a radical prostatectomy 10 years ago. I’m not going to assume I need to give [that patient] radiation.It is important that we do a better job of incorporating all of our available expertise. Patients should consult with a medical oncologist when they are at risk for recurrence or having some sort of biochemical recurrence, and they want to know what all of the available options of treatments and imaging are out there. For patients diagnosed with low- to intermediate-risk prostate cancer, they should see not only a urologist or a radiation oncologist, but see both so they can see both sides of treatment options.

The landscape of prostate cancer treatment has changed dramatically over the last 10 to 15 years. Fifteen years ago, we didn’t have much in the way of treatment besides maybe some docetaxel and hormonal therapy. Now, there are different ways to deliver that; there are different genomic tests we can offer. The community oncologist, having knowledge about all of these things that are available in our armamentarium for treating prostate cancer, is going to be key for them giving them optimal treatment and the options for the patients that are going to be seeing them.