Expert discusses advances, unmet needs across prostate cancer continuum

In this interview, Timothy A. Richardson, MD, discusses the 2024 Prostate Cancer Academy, which was held April 4-6 in Dallas, Texas. Richardson is the director of the advanced prostate cancer program, the co-director of the clinical trials division, and oversees the radiopharmaceuticals infusion program at Wichita Urology Group in Wichita, Kansas. He is also a board member of LUGPA, the national nonprofit urology trade association.

Timothy A. Richardson, MD

Could you highlight some key takeaways from the 2024 Prostate Cancer Academy?

One of the big topics was radiopharmaceuticals. Another one–and this is not new, it's a topic of every conference–is genetic testing. That's simply because we're not doing enough of it. We're not doing it early enough, and it is an opportunity to get these patients on targeted therapy. At every conference that we have, it continues to be a big point of emphasis and a big discussion.

As far as new things, the biggest topic out right now is radiopharmaceuticals, the targeted radioligand therapy. There's obviously a lot of change with lutetium coming out and some more down the down the pipeline, but that seemed like a big topic of conversation. There are some other things coming down the pike that was briefly mentioned, [such as] AR degradation, medications, things like that, but it was mostly the radioligand therapies.

At the meeting, you moderated the session, “Panel discussion: BCR, ADT, low volume disease.”¹ Could you discuss some key take-home messages from that session?

The new regimen that we're considering now in patients with high-risk, biochemical recurrence, non-metastatic disease comes from the EMBARK trial. Christopher Pieczonka, MD, did a very nice job of presenting that data, and my job as the moderator was to go over a few example cases with the with the crew as a radiation oncologist. Neal Shore, MD, FACS and Christopher Pieczonka, MD, were part of the panel discussion. The EMBARK trial gives us an opportunity to add enzalutamide along with ADT, and in certain situations, possibly enzalutamide monotherapy for these patients with high-risk, biochemical recurrence, non-metastatic disease. The data did show an improvement in the survival without developing metastatic disease or progression. That was a good discussion on different case presentations.

The real conundrum is that the EMBARK trial used conventional imaging. Today, we're not using a lot of conventional imaging; we're using a lot of PSMA PET scans. In these patients today where we're seeing very microscopic metastatic disease on the PSMA PET scan, those patients in the EMBARK trial would have been assumed to be non-metastatic because their conventional imaging was negative. So, one of the real big discussion points was, what do we do with those patients today? Do we treat them the same way as we would in the EMBARK trial? Or do we treat them differently because we see metastatic disease on the PSMA PET scan? There's not a right or wrong answer. I think a lot of us are falling back to that EMBARK trial because it gives us an opportunity to give the patient a treatment break at 9 months vs signing them up for an indeterminate length of time for treatment.

What future advancements or breakthroughs in prostate cancer do you anticipate in the next 5-10 years?

Most of the breakthroughs, I think, are still going to come in the metastatic space. That's just simply where all the research is. There's not a lot of research being done for these patients with localized disease. I think there's a lot of research being done in molecular testing, genetic testing, that can be used in patients with localized disease, but a lot of the therapeutic studies and research are being done within the metastatic space. I think the targeted radioligand therapy is going to take hold and gain earlier approval, so we'll be able to use it earlier and earlier in the disease process, potentially even with localized disease. There are some things looking at potentially using targeted radioligand therapy when the patient is not even metastatic. But certainly, there are more and more radioligands coming out not only in prostate cancer, but in other cancers related to urology, and I think that's going to be the next big wave. Certainly, you'll have other therapies like the AR degraders, combo therapy, and PARP inhibitors along with androgen receptor inhibitors–those things are always going to be there. But if you're looking at the class that stands to see the biggest growth over the next 5 years, it'd be the targeted radioligand therapy, in my opinion.

You had also mentioned that genetic testing was a big topic of conversation at the meeting. Could you touch on the importance of genetic testing for early detection and targeted treatment?

The low hanging fruit is doing genetic testing on the patients that have metastatic disease. That's level 1 NCCN guidelines; any patient that has metastatic prostate cancer should get somatic and germline testing. That's the low hanging fruit, but we need to go further. In these patients that have significant family history [and] those that have high-risk disease, there's a significant number of those patients that could be tested as well. We need some help with the payers and with the guidelines to push acceptance of testing in those spaces. Many times, we'll have a patient with a significant family history, or they have high-risk disease, and their commercial insurance plan doesn't cover the genetic testing. It's pretty standard in the patients with metastatic disease, but [not in] those patients with localized high-risk disease. I think the times need to move forward and allow for more genetic testing in those patients as well, especially in the patients that are in the high-risk population–[such as] African American [patients] with a strong family history and first-degree relatives. I think especially in those patients genetic testing can give a benefit.

Is there anything else you want to add?

There's always a big push for early access to screening [and] better screening, if you will. We saw a big downturn after 2012 when the [United States Preventive Services Task Force] downgraded PSA screening. [From that,] we saw a huge rise in metastatic prostate cancer, in advanced prostate cancer. Thankfully, I believe it was in 2017 to 2018, they changed that rating to a C, to a shared decision making. But I think there's still progress that needs to be made, especially in the high-risk patients. Those patients that are African American patients with a first-degree relative, family history are at higher risk, and I think some work could be done to change the grading for those patients. The Prostate Cancer Foundation recently had a panel of experts that that reviewed [over 200] literature reports, and came up with some guidelines and statements regarding Black patients and patients with first-degree relatives.² The conclusion was that these patients do benefit from PSA screening and prostate cancer screening at an earlier age. So, I think the guidelines need to be updated to allow for these patients to be screened as early as 40, and potentially even beyond the age of 70, depending on the patient's scenario.

References

1. Richardson TA. Panel Discussion: BCR, ADT, Low Volume Disease. Presented at: 2024 Prostate Cancer Academy. April 4 - 6. Dallas, Texas

2. Garraway I. Prostate Cancer Foundation (PCF) screening guidelines for prostate cancer in Black men in the United States. Presented at 2024 ASCO Genitoruinary Cancers Symposium. San Francisco, California. January 25-27, 2024. Abstract 264