The field of prostate cancer has experienced transformational change over the past decade, with new treatments and technologies revolutionizing detection and treatment. In an interview during the 2022 LUGPA Annual Meeting, Ashley Ross, MD, PhD, discussed these advances as well as unmet needs in prostate cancer. Ross is an associate professor of urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
Urology Hours: Could you describe some of the biggest unmet needs in prostate cancer, in your opinion?
Dr Ross: There have been many advances in prostate cancer, particularly over the last decade or so. Most of the unmet needs, at least in the short term, will have to do with the implementation of new technologies. If you think about screening tests, we’ve had a lot of new tools that have been used for prostate cancer screening, in diagnosing clinically significant diseases, different biomarkers that can tell people their risk, the use of imaging: the MRI should be standard before biopsies, including the techniques we use for biopsy, perhaps transperineal approaches that reduce infection or the need for antibiotics. If we look at the use of these across the country, they are nowhere near 100%. Certainly, there are also some health inequities that are stratified by socioeconomics, race, and location of the individual and physician.
Furthermore, if we look at advanced disease (cancers that have been detected and we know to be aggressive), there has been a lot of evidence that multimodal therapy for those men, even in the hormone-sensitive setting, shows that combining 2 or sometimes , even 3 agents can increase your overall survival. But the implementation of that has also been delayed. So that’s a life-saving therapy that hasn’t been used. If we ask, “What’s the path to the next level of discovery, pretending we’re implementing everything perfectly?” I think the border will be twofold. In the advanced environment, we have good tools that we can use in advance in the first and second line of therapy. But we still have to deal with the more androgen-insensitive, transformed cancers, particularly those that are moving into the neuroendocrine or small cell type. In the localized setting, it is about reducing morbidity. There have been some advances on the radiation side, there are some early signs that focal therapy may work. We are also constantly improving surgical approaches.
You talked a little bit about some of the emerging technologies and advances in the treatment of prostate cancer. Could you talk specifically about the emergence of PSMA-PET imaging and how it is transforming the field?
That’s a great question. For a long time in prostate cancer, we imaged it based on things like lymph node size or bone turnover, looking at technetium and MDP in MDP bone scans. PSMA-PET has been in development for a little over a decade, I believe. It has recently been approved in this country for staging and staging across the board; really, anytime you suspect there might be metastatic disease, either up front, at the time of recurrence, or at the time of disease progression. It has been shown in randomized trials to be more accurate in all settings and also more sensitive for detecting small amounts of disease. It’s just better. There is some preliminary evidence that it may improve decision making and outcomes for patients. What we know for sure is that it is simply a better image in terms of accuracy.
Right now, due to its superiority, PSMA-PET imaging should be the first thing you turn to when trying to determine if someone has metastatic disease. As I mentioned, there is still data that needs to be confirmed to see if using PSMA-PET imaging to guide your treatment decisions will lead to better overall patient outcomes or not. That is yet to be determined. There are some controversies there, but on a basic level, understanding where the cancer is in a person’s body and how much cancer is in the person’s body will lead to better management.
What do you think have been some of the major advances in prostate cancer discovery in recent years?
In recent years, I would say, as we mentioned, better imaging, particularly the use of PSMA tracers for PET imaging, has been a huge advance. The second big advance in the field of localized diseases and now a little bit in the field of more advanced diseases is the use of genomics and genetics, specifically molecular tests like Decipher that give you a better risk prognosis and guide you to make decisions of treatment. In the advanced setting, the most important thing has been to understand that upfront combinatorial therapies using androgen deprivation therapy, but also another androgen signaling inhibitor, perhaps even with chemotherapy in some cases, can improve overall survival . And then in the castration-resistant setting, there’s also the use of genetics to guide therapies like PARP inhibitors. Finally, there is the use of PSMA as a radioligand to deliver therapies such as lutetium PSMA. That has shown greater efficacy so far in late-stage disease in trials, but now it’s being tested in earlier-stage disease where I think the impact will be even greater; what I mean is previous lines of treatment.
Please discuss your own research in particular.
I cover the spectrum of what we just talked about. My research is very focused on using existing tools and implementing those tools and then running clinical trials. There was a point, maybe 5 or 10 years ago, where we were really very entrenched in discovering basic things. I had a wet lab where we did experiments with mice and genomics. Now, actually, we have many tools available. My passion has been, how do we use them correctly? And then when we are using them, how do we disseminate that knowledge? Obviously, the standard for how we use these things properly in humans is through trials, and the more we can put people into trials and do clinical trials, the better. For example, we have performed different PET imaging assays to analyze PET for staging and local disease identification. We are using PET/MR in those studies.
As far as risk stratification, I’ve done a lot of work with genomics, looking at gene expression and how that can guide treatment decisions, how it can stratify cancers into different subtypes. Now, there has been a new understanding that maybe we can use artificial intelligence in pathology to recognize some of these features in a higher throughput way. We’ve done a lot to bring our screening tools together and put them into different nomograms that can be easily used to identify your risk of having prostate cancer and if you need a biopsy. And then in more advanced staging, in partnership with industry, we’re doing a lot of trials on hormone-sensitive status to see if we can extend overall survival, maybe even removing some therapies, going to bimodal versus trimodal therapy. .