James is a professor of Prostate and Bladder Cancer Research, as well as a group leader in Prostate and Bladder Cancer Research, at The Institute of Cancer Research and The Royal Marsden Hospital, located in London, England.

Dr. Nicholas James 

Dr. Nicholas James discusses why it is important to identify which patients with high-risk prostate cancer will truly benefit from intensified treatment.

Understanding the Risk of Overtreatment in Prostate Cancer

It is important to target intensified therapy to patients who are most likely to benefit, thereby avoiding unnecessary treatment and toxicity in patients who are not likely to benefit from treatment. This message is highlighted in the STAMPEDE trial findings, which demonstrated that adding two years of Zytiga (abiraterone) to standard treatment for patients with high-risk, non-metastatic prostate cancer significantly reduced the risk of recurrence, according to Dr. Nicholas James.

To further discuss the topic, James sat down for an interview with CURE to discuss the importance of identifying which patients with high-risk disease will truly benefit from intensified treatment.

Why is it important to identify which patients with high-risk prostate cancer will truly benefit from intensified treatment? What have recent trials like STAMPEDE shown about adding Zytiga (abiraterone) to standard therapy in this population?

It's self-evident that if a patient receives a treatment they don't need, they will only experience side effects with no benefit. The way treatments tend to evolve — and as your question hints, this is true of all therapies, not just cancer therapies—is that we select a population of patients and hypothesize that a drug might work well for them. We then compare their outcomes with patients who did not receive the new treatment to see who fares better.

In the particular trial we're reporting results from here, we studied patients with aggressive prostate cancer — cancers with a high risk of spreading, but where, to our knowledge, the cancer had not yet spread. We know from experience that these patients have a high chance of recurrence after their initial treatment.

The patients we treated in this cohort had high-risk prostate cancer, meaning a very high risk of recurrence after initial treatment. The standard treatment for these patients involves two to three years of androgen deprivation, which switches off the production of male hormones, combined with a course of high-dose radiotherapy to the prostate and potentially to the pelvic lymph nodes if deemed necessary. Even with this approach, depending on how patients are selected, [the disease will ultimately recur in about] 30% to 40% of cases. Conversely, this also means that 60% to 70% of patients will do fine with the standard treatment.

In the STAMPEDE trial, which is apparently the only trial with mature results from this type of experiment, we took patients receiving standard treatment and divided them into two groups. Half received the standard treatment, while the other half received the standard treatment plus two years of a hormone therapy drug called Zytiga. Zytiga is approved for use in metastatic prostate cancer — prostate cancer that has spread. Initially, it was used in patients whose cancer had recurred after initial treatment, essentially as a palliative treatment.

Subsequently, based on my own trial, STAMPEDE, and a second trial called LATITUDE, we found that it worked better when given to newly diagnosed men with metastatic disease. On average, they lived about a third longer than patients for whom we reserved Zytiga or similar drugs for later use. So, if you are diagnosed with widespread disease, drugs like Zytiga, and a number of others with similar results, are part of the standard of care. However, if you have disease that might spread but hasn't yet, there's much less data, and STAMPEDE is the only trial that has provided data on this.

What we found was that giving just two years of Zytiga treatment to this high-risk group of men halved the risk of the cancer recurring after treatment concluded. These men received a fixed period of treatment—two to three years — and then stopped all treatment. We observed that even five years later, the relapse rate remained halved, which is a great result. As you might expect, if you don't relapse, you are not very likely to die from prostate cancer, and this translated into a 40% improvement in the risk of death from prostate cancer. This is a truly significant finding.

Transcript has been edited for clarity and conciseness

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Dr. Nicholas James

Understanding the Risk of Overtreatment in Prostate Cancer

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