William K. Kelly, DO, discusses the evolving imaging techniques and emerging therapeutic approaches in prostate cancer.
William K. Kelly, DO
Developments in screening and localized treatment for prostate cancer are two components that have been part of the prostate cancer field’s transformation, explains William K. Kelly, DO, adding that treatment of these patients must involve a multidisciplinary approach. “Prostate cancer is not 1 disease; it is [made up of] multiple diseases and it takes multiple people to treat a patient,” Kelly said.
With regard to active surveillance, the United States Preventative Services Task Force (USPSTF) released draft recommendations in April 2017 that physicians should have decision-making conversations with their patients aged 55 to 69 regarding the benefits and risks of prostate cancer screening. This differs from the USPSTF’s previous opinion, which was against routine prostate-specific antigen (PSA) screening for the disease.
Novel imaging approaches, such as prostate-specific membrane antigen (PSMA)-PET scans, could revolutionize the paradigm, he says, to track microscopic disease in a particular area as the technology has high-detection sensitivity rates.
In an interview during the 2018 OncLive® State of the Science SummitTM on Prostate Cancer, Kelly, professor, director, Division of Solid Tumor Oncology, Thomas Jefferson University Hospital, discussed the evolving imaging techniques and emerging therapeutic approaches in prostate cancer.Kelly: It starts off with localized disease; we are really starting to rethink what we can do with [that setting]. In the meeting, Dr Edouard Trabulsi introduced the fact that, even in patients with locally advanced disease, there is a role for local control of tumor. We forgot that before because, in all of the other tumor types, we have maximized local control of the tumor.
Years ago, we swung away from that. Anybody who had a locally advanced prostate cancer we shied away from [doing] local disease control on them. There is a swing backwards—even in those patients who had micrometastatic disease. We are now doing surgery in those patients because it does give optimal local control. However, it also brings up the multimodality approach that is approaching with prostate cancer.When you see a task force go back and forth, that means there are limited data to guide them; there are not black-and-white data, it’s really gray. There are a lot of things that go into a decision about active surveillance—not only about the tumor type, but it is based on anywhere from the pathology to the genomics to other characteristics. We have to also include the patient preferences because they actually drive [the decision]. We need to understand patient preferences and their comorbidities.
There are some studies coming out that are trying to define those prostate cancers [for active surveillance]. We [need to continue our] understanding that prostate cancer is a very heterogeneous disease, both in the characteristics of the primary tumor but in individual patients also. They are first in shock and say, “What do you mean I have cancer?” But it is a better understanding of cancer. It is a societal problem in the United States, because if you go to Europe, they are much more accepting of active surveillance. Here in America, we have hyped it up too much and we're doing some “back stepping” to diffuse it. Now it’s, “If you have a low-grade cancer, that’s okay, we can monitor it." We have much better tools that we can actually use to make patients more comfortable now for active surveillance. It is much more acceptable nowadays than before. That is an evolving area right now. We are trying to understand which tumors are truly oligometastatic, which means a limited number of sites versus those who have more diffuse metastatic disease that is not seen on common imaging right now. With the new imaging agents that we have, such as the PSMA-PET scans or the Axumin [fluciclovine F 18] scans, these are showing much more microscopic disease defined in that area. However, you still have to think about treating these patients aggressively, because there is a small set of them that possibly can be cured with aggressive treatment. Right now, it has not infiltrated the United States as much as Europe and Australia, which are the 2 leaders in the area right now. It has really changed their practice greatly over there. It will influence us greatly in the future because this is a much more sensitive test. However, what we're really waiting for is to understand how to use them better, when to use them, and how they are going to direct treatment decisions, so they actually improve patient benefit. Everybody has been excited about immunotherapy. There are immune therapies everywhere; however, it hasn’t been true in prostate cancer. We need to understand the disease a little better to develop immunologic approaches to prostate cancer and there are ways that we're starting that. However, at the end of the day, we have to have better drugs and a lot of the drugs we have right now are a continuation of what we have done before. We have to break out of that mold and find new targets and drugs for prostate cancer. One of the [challenges with] immune therapy is that we are dealing with a cancer that has been there for a long time. We have an older population and some immune tolerance that has built up over time. We have to understand the microenvironment that is associated with prostate cancer and try to develop therapies that are related to this older population that may be immune-tolerant. We work on a lot of different things. We have many targeted therapies that are going on right now; we are looking at new targets that look at N-terminal domain of the androgen receptor. We are looking at other factors that inhibit the chemokines and cytokines, which could delay metastatic disease, but we are every interested in understanding the biology of prostate cancer. We have developed techniques that will help us understand how the microenvironment impacts prostate cancer.
It is really a multidisciplinary team. I work with more than 28 investigators who are basic scientists, population scientists, et al. The other thing is that if we're going to have an impact on prostate cancer, we have to understand the population a little better. In Philadelphia, we have one of the highest rates of prostate cancer. African-American patients die 3 times faster than whites in this area. One of our issues is why there is such disparity between them in this area, and much of our effort is going to the neighborhoods and trying to find that out.