Alan H. Bryce, MD, is the chief clinical officer, a professor in the Department of Molecular Medicine at the Translational Genomics Research Institute, and an oncologist at City of Hope Cancer Center Phoenix.

 Dr Heath, generally, how has the treatment landscape for prostate cancer evolved in recent years? All of us on this call have been doing it for several years, and it is different today than it was even 3 years ago, let alone 5 or 10. But where do you see, in terms of new treatment options, the greatest progress being made?

 We’ve been talking about it with PSMA [prostate-specific membrane antigen]-based treatment. The theragnostic approach after we diagnose, and we do a lot of handwringing about what to do with what’s been seen or not seen; you can’t unsee what you just saw. It’s making for very robust MGT [multidisciplinary team] meetings in most hospitals and institutes, but also in practice. There’s excitement that when patients and physicians see the target, and now there’s a drug to get to the target, there’s a sense of satisfaction with that. The world of genomic sequencing has already changed what we do. I think it’s now, what do we do with this information? We’re asking harder and deeper questions, and that’s exciting because it’s great for a group of drugs, but there will be more coming that will also use this type of approach. Even just with single agents, how to navigate is complicated, but then putting things together and getting in all sorts of other interesting discussions, like whether we should put them together, and for everyone or for a select group? It becomes the new way to think about prostate cancer. With our other colleagues with lung cancer and more molecularly based tumors that are treated, their conversations and conferences are a little different than what we’ve been doing.

I think we’re getting there, but our conversations are quite varied because it’s not knowing what it is, it’s using the data for when, so in some sense, it’s a bit more complicated because we have a lot of options, and it comes down to how many of our patients will get it all. There are data to show that second and third line, and there are a lot of folks out there still not getting treated, which is astonishing when you have all these different agents, but it makes our approach in the beginning critical. Starting from when you’re about to propose, and what are you going to do in the primary setting with locally advanced or local cancer. Everyone is having this conversation early so that we know the strategy, but it’s exciting times for sure.

Videos

Key opinion leaders provide a broad perspective on recent shifts in the treatment landscape for prostate cancer. 

Recent Progress in the Prostate Cancer Treatment Landscape 

 Dr Zhang, what about unmet needs or knowledge gaps in this space? There are a lot of knowledge gaps with a new technology, but what comes to mind?

 Sure. [Declan] Murphy, [MBBCh,]at ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] had a nice slide that pointed out, are we historic imagers, are we novel imagers? Using PSMA PET [prostate-specific membrane antigen positron emission tomography] allows us more accurate diagnosis, and we’re able to pinpoint disease. But how much of that information are we using today to confer our treatment selection, and also in terms of helping our patients understand what is needing to be treated, and what we would not have seen in the past? Our prior trials were all based on conventional imaging. I think that gap is an unmet need and an opportunity. In PSMA-positive disease, there are patients in the localized high-risk setting who are going to have some evidence of metastatic spread, whether that’s nodal or to a bone, but that is not clearly apparent on our conventional imaging. Those patients may be intensified with systemic treatment, and that’s not wrong in our current landscape. We can see that there’s metastatic disease. But how many of those patients are overtreated by adding that systemic treatment? I don’t think we know that answer.

The other possibility is that in our potentially oligometastatic disease by conventional imaging, those patients may be upstaged further by showing more sites of disease, so higher disease burden. If we were going to consider metastasis-directed therapy or treatment of the prostate bed for those in the salvage setting, and we skipped those treatments that potentially have life-prolonging benefit, then perhaps we are undertreating a portion of patients. There are gaps in what we know right now and how we practice for our patients. Hopefully, we are all being careful in trial design in order to show in prospective studies how to best treat these patients going forward.

 Absolutely. One of the things I always try to emphasize with my patients is to say the imaging does not change the biology. It shows us what the disease is doing more clearly, but the disease was doing this whether we imaged it or not. The imaging isn’t changing the outcome, it’s just giving us more information by which to make our decisions. I think Dr Lowentritt’s point is one of the important ones of not overcalling disease. There are false positives, so we never want to deny a patient a chance at cure by overcalling a false positive on a scan. That’s probably the part I worry about most. I don’t worry so much about 19 metastases vs 17, conventional imaging vs PSMA, but it’s the patient who we label as incurable, that’s the one I worry about. That’s probably the biggest point of caution I would emphasize for the audience.

Medical oncologist Tian Zhang, MD, outlines the remaining unmet needs and knowledge gaps surrounding imaging of prostate cancer. 

Prostate Cancer Imaging: Unmet Needs and Knowledge Gaps 

 titled, “Key Updates in Nonmetastatic and Metastatic Prostate Cancer Treatment.” I’m Alan Bryce from the Mayo Clinic in Arizona, a professor of medicine, medical oncologist, and director of the Mayo Clinic Comprehensive Cancer Center here [in Phoenix,] Arizona. I’d like to welcome my esteemed fellow panelists to introduce themselves. We’ll start with Dr Elizabeth Heath.

 Hi everyone. Thanks for joining. My name is Dr Elizabeth Heath, I’m a professor of oncology at the Karmanos Cancer Institute in Detroit, Michigan. I’m also the associate center director for translational sciences. Thanks for having me.

 Hi, my name’s Ben Lowentritt, I’m a urologist practicing at Chesapeake Urology in [Baltimore,] Maryland, and the director of our comprehensive prostate cancer program. Thanks for having me.

 Hi, everyone. I’m Ed Posadas, I am the codirector of the experimental therapeutics program at Cedars-Sinai [Samuel Oschin Cancer Center] and the medical director of the urologic oncology disease research group for the Center for Urologic Research Excellence at Cedars-Sinai [in Los Angeles, California]. I’m happy to be here.

 Hi, it’s great to be here with everyone. I’m Dr Tian Zhang, I’m chief medical oncologist and associate professor at UT Southwestern Medical Center in the Harold C. [Simmons] Comprehensive Cancer Center in Dallas, Texas.

 Excellent. Welcome everyone, and thank you for joining me. Today we’re going to discuss several recent updates in the treatment of patients with nonmetastatic and metastatic prostate cancer that were presented at key conferences within the past couple of years. We’ll discuss the data in the context of guidelines, the existing treatment landscape, and potential impact on clinical practice. Let’s get started on our first topic. In the first module, we’re going to talk about recent paradigm shifts in prostate cancer. We’ll go around the panel here and start with Dr Heath. What do you think some of the most significant advances are in imaging for prostate cancer?

 I think we could start this conversation with PSMA [prostate-specific membrane antigen]. Those 4 letters have changed our landscape, whether it’s for imaging or for treatment. That’s a recent development. As many of us remember, it’s the start of something, and when the initial Gallium 68 PSMA was announced in December of 2020, it was then followed by Pylarify [piflufolastat F 18], and then again with the actual indication with the lutetium-177 compound. With the advent of that, all of our conversations shifted quite dramatically.

 Fair enough, absolutely. Considering how it’s impacting our daily practice, Dr Lowentritt, from a urology perspective, how about at initial diagnosis? How can clinicians use PSMA PET [positron emission tomography] in the initial setting now?

 There’s been a rapid acceptance among clinicians that we have superior staging imaging now. For those patients who are high risk, and select unfavorable/intermediate-risk patients, it makes sense for any patient you would consider imaging to consider one of the novel PSMA PET agents. We see more entrants coming every month, and another one likely coming with a radio-hybrid PSMA. Some of the results were shared at the recent ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] meeting that suggested we can get good true detection rates out of these PET scans with patients who otherwise we’d be considering for imaging prior to therapy. It’s becoming an essential part in helping us adequately stage our patients and cater the treatment as needed.

 What are the difficulties with using PSMA PET in that initial setting?

 The first and foremost hurdle is the insurance coverage, which we unfortunately still must deal with. Otherwise, you must make sure you have imaging readers that are comfortable. You must make sure you know what you’re looking for and where you’re looking for the most likely yield for finding disease. We still see some strange findings that are unlikely cancer-related but lead to some handwringing. I think we’re introducing some uncertainty with a new agent, but in general, the information we get is helpful in patients that can alter therapy and maybe save them some degree of adverse effects or potentially increase their chance of long-term response. I think we’re getting there with our ability to finding out who we can most benefit early.

 Dr Posadas, what about the guidelines, are they helpful at this point? And where can clinicians look when trying to decide whether to use conventional imaging or next-generation imaging in prostate cancer?

 This is a good question, and it rolls into what Dr Lowentritt was speaking to, which is that there’s now incorporation of PSMA-based imaging into guidelines like the NCCN [National Comprehensive Cancer Network]. There are additional guidelines like RADAR [Radiographic Assessments for Detection of Advanced Recurrence] VI that have come out. The payers have not always taken these to heart because they ask a question about how this is impacting survival, and they may put up a fuss, which is a bit frustrating because we as clinicians have seen value. But until certain things read out with end points, it’s going to become more difficult. It’s exciting to see this move forward. It opens up new opportunities for patients. Hopefully those of us involved in the guideline formation can further push the importance of this type of imaging for our patients, both with metastatic and nonmetastatic prostate cancer, to get further insight into both the staging and the molecular nature of their disease, which helps guide important decision-making.

Five expert panelists in prostate cancer consider how recent advances in imaging, particularly PSMA-PET, have impacted the field, and highlight guidelines that may aid clinicians in selecting amongst the available imaging modalities.

Breakthroughs in Imaging Modalities for Prostate Cancer 

Edwin M. Posadas, MD, medical director, Urologic Oncology Program, co-director, Translational Oncology Program, associate professor of medicine, Cedars-Sinai Medical Center, discusses unmet needs in prostate cancer.

The main factor, Posadas says, is identifying the best treatment for a patient before they get to the point of requiring treatment with abiraterone acetate (Zytiga) and docetaxel. Circulating tumor cell assays and new imaging technologies may enable oncologists to do this in the future, but it won’t come in the near future. With that being said, identifying lethal forms of prostate cancer as early as possible is the biggest urgency in the field right now. Effective treatment is available for early-stage prostate cancer.

The second unmet need is understanding the entities of nonandrogen receptor (AR)-driven prostate cancers. For the last 70 years, Posadas says, physicians have relied on AR signaling to control prostate cancer. What’s likely to become a bigger problem in the future, Posadas adds, is that as these agents are used earlier in the natural history of the disease, what emerges after resistance is a more aggressive prostate cancer.

Dr. Posadas on Unmet Needs in Prostate Cancer

Edwin M. Posadas, MD, medical director, Urologic Oncology Program, co-director, Translational Oncology Program, associate professor of medicine, Cedars-Sinai Medical Center, discusses the future of early detection in metastatic castration-resistant prostate cancer (mCRPC).

Though some medical centers will take a biopsy of the prostate every month, asking for a blood draw is less invasive. Physicians debate the use of with prostate-specific antigen (PSA) within the prostate cancer field; however, it can be useful tool for a large subset of tumors, Posadas explains.

However, there are many tumors that don’t produce PSA or have alterations that PSA does not reflect. In these cases, something like a circulating tumor assay may be complementary and add information that PSA testing may not provide. The combination has given physicians new insights into how prostate cancer behaves.

Edwin M. Posadas, MD, medical director, Urologic Oncology Program, co-director, Translational Oncology Program, associate professor of medicine, Cedars-Sinai Medical Center, discusses the future of detection in metastatic castration-resistant prostate cancer (mCRPC).

Edwin M. Posadas, MD

Articles

Recent Progress in the Prostate Cancer Treatment Landscape

Prostate Cancer Imaging: Unmet Needs and Knowledge Gaps

Breakthroughs in Imaging Modalities for Prostate Cancer

Dr. Posadas on Unmet Needs in Prostate Cancer

Dr. Posadas on the Use of Circulating Tumor Cells in mCRPC