Changing the Oligometastatic Prostate Cancer Landscape Using Novel Therapies

Oligometastatic prostate cancer is a difficult disease to treat, as urologists and oncologists still define subgroups of patients based on metastases and how best to manage them. William K. Oh, MDdiscusses this complex disease state in a recent presentation given at the New York GU 2022 Interdisciplinary Congress on Prostate Cancer and Other Genitourinary Malignancies.1 In the following interview, he summarizes the main points of his presentation as well as emerging research in this area. 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 presentation.

Oligometastatic disease in prostate cancer is actually a very hot topic right now, as new studies suggest that radiation therapy directed at metastases can delay cancer progression. Additionally, we recognize that our imaging for prostate cancer has been suboptimal for many years. Bone scans and CT scans have served us well, but they have always underestimated the disease. And one of the reasons we know they underestimate the disease is because the PSA [prostate-specific antigen] told us that the patients were progressing. And yet sometimes the source of the metastatic progression is not found. So I think what we’ve learned is that the degree of metastatic disease is actually underestimated by traditional imaging. And now, with new PET imaging, we have a greater ability to identify metastases. It’s in this 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 metastases [hormone-sensitive prostate cancer (mHSPC)]. There are now many studies that have shown that these doublets and triplets are better than ADT alone. So I think there’s no doubt at this point that most patients who present with de novo metastatic disease should not just receive ADT alone. I understand that in many practices they still view ADT alone as the only choice for their patients. But I think the evidence is so strong that these patients should be given either a secondary drug, like AR-targeted therapy, or apalutamide [Erleada]enzalutamide [Xtandi]abiraterone [Zytiga]or docetaxel chemotherapy, and now docetaxel plus darolutamide [Nubeqa], that these have changed the way we manage these patients. But, for example, the question of whether patients with less than 4 metastatic lesions should receive chemotherapy – this is obviously something that came out of the CHAARTED study. [NCT00309985]— really raises the question of whether there is an optimal way to approach these patients. Should they receive dual or triple therapy for mHSPC, but also receive radiation therapy for primary and oligometastatic lesions? These are questions that I believe have yet to be resolved. In general, patients should receive, at a minimum, ADT plus additional systemic therapy for mHSPC and should be considered for additional treatments, such as radiation therapy to a primary site and to oligometastatic lesions.

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

I think that we will see in the next few years a greater definition of the different cohorts. For example, should a patient with a certain type of metastasis receive certain types of therapy? Should they receive chemotherapy or not? Should they receive targeted AR therapy in combination with chemotherapy? Should they receive treatment for both the primary site and the oligometastatic lesions? There is also biology that we will understand more and more. Not all prostate cancers are created equal. There are patients who are guided by the AR pathway, and others who are not, some who are neuroendocrine and poorly differentiated, where AR targeted therapy may not be the right treatment for them and may simply add a additional toxicity. And radiation therapy, of course, has been proven as a treatment option for many, many years, but we still don’t fully understand how targeted radiation therapy to metastatic lesions actually prolongs overall survival. We know this can hold back progress, but I think this is the million dollar question we need to address over the next few years.

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

I think the most important thing is to remember that in order to do what’s right for your patient, use the data we have. I would generally prefer to offer more therapy if the patient is fit and able to receive these treatments, as we know that the combination of systemic and local therapies is usually associated with the best overall outcome. What this means to me, for example, if a patient presents with oligometastatic metastatic disease – metastatic, but only 2 or 3 lesions – usually I’m going to err on the side of considering primary prostate treatment, which has been demonstrated from STAMPEDE [NCT00268476] potentially beneficial in patients with relatively few metastases. I would strongly consider radiating oligometastatic sites. This is 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 think our audience should know about this topic?

I think there’s a lot going on in terms of new imagery. For example, PSMA PET has now been approved for use in the United States. This changes our ability to identify what oligometastatic disease even means. I also think we’ve obviously had fluciclovine PET for a number of years and we have these new systemic options that show more and more that early use of these drugs can matter in terms of better long term outcomes . I think one of the issues is that we run out of treatments for a lot of these patients at some point. We also want to focus on the quality of life of our patients. So I think the most important thing to remember is [to] keep all these options open, try to use these new technologies as they arise, and seek out research that helps guide the best clinical care for our patients.

Reference

1. Oh W.K. Oligometastases in prostate cancer. Presented at: 2022 New York GU Interdisciplinary Prostate Cancer Congress and Other Genito-uriary Malignities; New York, New York. March 11-12, 2022

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