New Approaches to Localized Prostate Cancer Combat Overtreatment

Mark Emberton, MD

Both the diagnosis and treatment of patients with localized prostate cancer have recently been re-evaluated in an effort to address overtreatment. According to Mark Emberton, MD, FRCS, the most important factor for diagnosis is location, as it provides information to help decide how soon to treat or whether active treatment is necessary.

“Before you stick a needle in the organ, ask the question, ‘Where is the cancer?’ Just asking that question provides those extraordinary benefits,” Emberton said. “This is not a 10% or even 20% difference. This is a 100% difference in detection rates, which is lowering the risk of insignificant disease.”

OncLive: How has the diagnosis of localized prostate cancer evolved over the last few decades?

In an interview with OncLive, Emberton, professor of Interventional Oncology, Division of Surgery and Interventional Science, University College London, clinical director, Clinical Effectiveness Unit, Royal College of Surgeons of England, discussed updates in the diagnosis and treatment of patients with localized prostate cancer.Emberton: It hasn't been a good story, actually. For the last 40 years, the prostate has been unusual in that we have been [testing] men at risk of developing prostate cancer with a random needle deployment of the organ, which we don't do in organ systems in relation to cancer. I think we always knew that it is was unreliable and the diagnosis was uncertain, but I don't think we realized to what degree.

In the last 10 years, the role of imaging has been addressed, and has provided us with location for the first time in the last 100 years. This exposed the deficiencies that we had to live with historically. The worse deficiency was missed cancers, so we told people they were clear when they were not. The second worse deficiency was misdiagnosed cancers, and the third was diagnosing men with low-risk disease, which is an overdiagnosis.

Has a focus on multidisciplinary care helped in this communication?

The ideal pathway would correct all of those errors. This analysis discusses the degree to which deriving locations has helped us resolve those errors. In summary, it doubles the risk of detecting clinically significant prostate cancer, which is astounding. Over the last 10 years or more, we have been missing half of the men with clinically significant disease, so it is not surprising that many of our treatments don't work. We also will mitigate the problem of overdiagnosis to a large degree.There is no question that bringing in a mixed set of skills to a task results in benefit. It is quite interesting to look at my own professional relationships over the last 10 to 20 years. They have not been with other urologists, they are cross-disciplinary. My best friends are radiologists and pathologists because they are the people that I need in order to get the risk stratification right. One reason that we, as a unit, have been successful and able to research and innovate in the space is that we have had a team of superb radiologists that we work with constantly.

They give us a target, we verify the target, and we give them feedback on the validity of that target. The result is that detection rates go up, which means that we biopsy fewer men. The men that we do biopsy are very likely to have cancer. We are now getting up to detection rates of 80%, whereas historically, they have been in the order of 25% to 30%. It just shows how inefficient the system was before.

Considering the history of overtreatment, what is the current treatment of patients with localized prostate cancer?

Going forward, those relationships are going to have to expand, and we are starting to talk to our engineering colleagues and our computational biology colleagues. Interestingly, molecular medicine now with biomarkers is becoming increasingly important. Synthesizing all those bits of information, such as complex imaging data sets with biomarker data sets, is going to be the challenge for the next 10 years. The beauty of the new diagnostic pathway is that it does most of the work for us. It gets rid of men with low-risk disease; they cease to exist. We resolved the overdiagnosis issue there.

What has happened is that most of the patients who now present will have clinically significant disease. By deriving location, we don't necessarily have to treat them right away. Part of the impulse to treat was to correct the inherent error that we knew existed. If you did not know how much disease was there, by treating it, the risk of undertreatment was avoided. However, the result was overtreatment.

Now, a man comes to us who is at risk, we do some imaging, discuss it with him, and decide whether to biopsy the lesion. If we biopsy it and it is of moderate risk, we may decide to watch the lesion. If it grows, we may decide to treat it. Knowledge of location has been the most important variable that we have had in the last 10 years. It has changed our therapeutic target from the organ to the cancer. It is interesting to see radiotherapists now planning around the cancer, where they used to plan around the organ. They can get more dose on the cancer, and less elsewhere.

It seems this is turning into a more individualized approach for prostate cancer treatment.

What is your take-home message on the current state of diagnosis and treatment of localized prostate cancer?

Historically, everyone would get the same operation, and now, the operation can be adjusted based on location. The surgeon can go wide where the cancer is, and then try to preserve as much tissue as possible. That is exactly right. If you look at the historical pathway, it was very linear; everyone got the same treatment independent of grade, volume, location, and multiplicity. It was a one-size-fits-all approach, which is easier to implement. What I have described is much better for patients and healthcare systems, but it is complicated to implement. Everyone gets a slightly different treatment, which means that judgements have to be made all along the pathway. Those judgements are best made in a multidisciplinary setting. In early disease, the most important thing is to try and derive location with imaging. Currently, it is magnetic-resonance imaging, but there may be other ways to do that in the future. We are beyond evidence, and are now into the implementation and quality control phase. There will still be people struggling to get decent images, which is probably similar to mammography in the early days, before it was centralized, or radiologists specialized in that area. It is early days, but the challenge for the next 5 years is getting the quality up so that it does not matter where the patient goes; they will be exposed to high-quality imaging. This will provide the information required to allocate the treatment efficiently and effectively.