Changing the landscape of oligometastatic prostate cancer using novel therapies

Oligometastatic prostate cancer is a disease that is challenging to treat, as urologists and oncologists are still defining metastases-based subgroups of patients and how to best manage them. William K. Oh, MD, discusses this complex disease state in a recent presentation given at the 2022 New York GU Interdisciplinary Prostate Cancer Congress and Other Genitourinary Malignancies.¹ In the following interview, he summarizes the main points of his presentation along with emerging research in this space. Oh is a clinical professor of medicine at the Icahn School of Medicine, Mount Sinai in New York, New York.

Please summarize the main points of your talk.

Oligometastatic disease in prostate cancer is actually a very hot topic at this time, as new studies suggest that metastasis-directed radiotherapy can delay cancer progression. Also, we recognize that our imaging for prostate cancer has been suboptimal over many years. Bone scan and CT scans have served us well, but they've always underestimated disease. And one reason why we know that they underestimate disease is because the PSA [prostate-specific antigen] has told us that the patients are progressing. And yet, sometimes we can't find the source of the metastatic progression. So, I think what we've learned is the degree of metastatic disease is actually underestimated by traditional imaging. And now, with newer PET scan imaging, we have a greater ability to be able to identify metastasis. It's in that context that something else has happened, which is that we have new therapies, both AR-targeted therapies as well as the use of SBRT, or targeted radiotherapy, that have changed the landscape.

How will the rise of doublet and triplet therapies affect the treatment and management of prostate cancer in the future?

Recently we learned at GU ASCO, that the combination of androgen deprivation therapy (ADT) plus chemotherapy plus darolutamide is better than the combination of chemotherapy plus ADT in metastatic [hormone-sensitive prostate cancer (mHSPC)]. There are many studies now that have shown that these doublets and triplets are better than just ADT alone. So, I think that there’s no question, at this juncture, that most patients who present with de novo metastatic disease should not just be receiving ADT alone. I understand that in many practices, they still do consider ADT alone as the only choice for their patients. But I think the evidence is so strong that these patients should be receiving either a secondary drug, like an AR-targeted therapy, whether it’s apalutamide [Erleada], enzalutamide [Xtandi], abiraterone [Zytiga], or docetaxel chemotherapy, and now, the combination of docetaxel plus darolutamide [Nubeqa], that these have changed the way we manage these patients. But, for example, the question of whether patients with fewer than 4 metastatic lesions should receive chemotherapy—that was obviously something that came out of the CHAARTED study [NCT00309985]—really brings up the question of whether there's an optimal way to approach these patients. Should they get doublet or triplet therapy for mHSPC but also receive radiotherapy to both the primary and the oligometastatic lesions? Those are questions that I think are still left to be resolved. In general, patients should be receiving, at the very least, ADT plus an additional systemic therapy for mHSPC and should be considered for additional therapies, such as radiation to a primary site and to the oligometastatic lesions.

What further research would you like to see in this space?

I think we're going to see in the next few years a greater definition of the different cohorts. For example, should a patient with a certain kind of metastatic pattern receive certain kinds of therapies? Should they receive chemotherapy or not? Should they receive AR-targeted therapy in combination with the chemotherapy? Should they receive treatment to both the primary site and the oligometastatic lesions? There's also biology that we're going to understand more and more. Not all prostate cancers are created equal. There are some patients who are driven by the AR pathway, and some that are not, some that are neuroendocrine andpoorly differentiated, where AR-targeted therapy may not be the right treatment for them and may just add additional toxicity. And radiation, of course, has been tried and true as a treatment option for many, many years, but we still don't fully understand the degree to which targeted radiotherapy to metastatic lesions actually prolongs overall survival. We know that it may delay progression, but I think that's the million-dollar question that we have to resolve in the next few years.

What advice would you give to fellow urologist/oncologist on managing this complex group of patients?

I think the most important thing is to remember that, in an effort to do what's right for your patient, use the data that we have. I would generally err on the side of offering more therapy if the patient is fit and able to get these treatments, because we know that both the combination of systemic and local therapies is usually associated with the best overall outcome. What that means to me is, for example, if a patient presents with metastatic oligometastatic disease—metastatic, but just 2 or 3 lesions—in general, I will be erring on the side of considering primary therapy to the prostate, which has been shown from STAMPEDE [NCT00268476] to have potential benefit in patients with relatively few metastases. I would be strongly considering radiating the oligometastatic sites. That's in addition to the use of ADT, but also the use of at least 1 AR-targeted therapy in most of these patients.

Is there anything else you feel our audience should know about this topic?

I think that there's a lot going on in terms of new imaging. For example, the PSMA PET has now been approved for use in United States. It's changing our ability to identify what oligometastatic disease even means. I also think that we've obviously had the fluciclovine PET for several years and we have these new systemic options that are showing more and more that earlier use of these drugs may matter in terms of better long-term outcomes. I think one of the problems is we do run out of treatments in many of these patients at some point. We want to also focus on quality of life for our patients. So, I think the most important thing to remember is [to] keep open all of these options, try to use these new technologies as they come, and look out for research that helps guide the best clinical care for our patients.

Reference

1. Oh WK. Oligometastases in Prostate Cancer. Presented at: 2022 New York GU Interdisciplinary Prostate Cancer Congress and Other Genitourinary Malignancies; New York, New York. March 11-12, 2022