Expanding Radioligand Options Redefine mCRPC Management and Individualize Patient Care

As new radioligand agents reshape the prostate cancer treatment paradigm, these rapid advances in prostate cancer management underscore the importance of patient-centered care discussions, according to Alicia Morgans, MD, MPH.

In an interview with OncLive®, Morgans highlighted the current role of radioligand therapies for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and emphasized the importance of shared decision-making with patients in prostate cancer management, especially with the increasing number of treatment options.

She also discussed the clinical applications of radium-223 plus enzalutamide (Xtandi) in patients with mCRPC in another part of the interview.

Morgans is a genitourinary medical oncologist and director of the Survivorship Program at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School in Boston, Massachusetts.

OncLive: Where do radioligand therapies fit into the mCRPC treatment paradigm?

Morgans: Lutetium Lu 177 vipivotide tetraxetan [Pluvicto] is the currently available radioligand therapy that is a PSMA-targeted agent available in a heavily pretreated, post-chemotherapy and now prechemotherapy mCRPC setting.¹ We are enthusiastically awaiting the first-line use of this agent in [patients with] metastatic hormone-sensitive prostate cancer. We expect to see [the phase 3 PSMAddition trial (NCT04720157) of the agent in this setting] report out soon, because we’ve heard that it may be a positive trial.² In that trial, [in patients with] metastatic hormone-sensitive disease, lutetium Lu 177 vipivotide tetraxetan is added to androgen deprivation therapy [ADT] and an androgen receptor pathway inhibitor [ARPI] vs ADT plus an ARPI [alone]. [Those data are] going to be interesting.

This agent is being assessed in various additional areas. The radioligand therapy area is one that we are going to see a lot of change and advance in over the next few years, because the drugs that are being developed may use lutetium 177 as a radioactive component, but some of them are using other agents, like actinium 225, copper, or lead. There are multiple radioactive moieties that are being used and delivered to prostate cancer cells, including beta-emitting ones such as lutetium 177, as well as alpha-emitting ones. One of the most advanced there is actinium 225. We may see these different options open up for us.

We also see that [investigators] are targeting different proteins or different parts of the cancer that might also give us new opportunities [beyond the] PSMA protein. There’s a lot going on in radioligand therapy. There’s a lot of discovery and a lot of learning from a clinical perspective and from a patient perspective. We should keep our eyes on this, because this area of care is destined to change rapidly over the next few years.

What factors influence your decision to use radioligand therapies in your practice?

We use radioligand therapies in patients in part of a shared decision-making process. For patients with advanced disease, [such as] those who have already received chemotherapy and some who may have already received radium-223, we’re considering using treatments like lutetium Lu 177 vipivotide tetraxetan, but integrated earlier [into the treatment paradigm]. Importantly, one size does not fit all. Even when it comes to radioligand therapies, there’s a lot of enthusiasm around PSMA-targeting agents, but they’re not necessarily the best treatment for every patient, and we have conversations with patients about all their options. These include chemotherapy, radium-223, a PARP inhibitor, or a PARP [inhibitor–based] combination, depending on the patient’s germline and somatic genetic testing [results]. Any of these could be options, or perhaps a clinical trial might be of more interest or a better fit for an individual patient.

Many patients are using radioligand therapies, particularly lutetium Lu 177 vipivotide tetraxetan, earlier [in the treatment course], but we are also still using radium-223, chemotherapy, and everything else. Having open and candid conversations about all the aspects of treatment, including monitoring dosing frequency, [being aware of] whether [the treatment is administered] orally or intravenously, [knowing] what the adverse effects are, [and knowing] what the restrictions may be regarding radiation safety, when it comes to the radioligand therapies, are all important considerations for patients. We end up using [radioligand therapies] at various points across the spectrum after these long and important conversations with patients, as well as with their families.

How do you integrate patients’ goals and preferences into your treatment decision-making strategies?

Shared decision-making is still a critical part of prostate cancer care and may be increasingly important as the number of treatment opportunities continues to grow. All these nuanced details end up coming into play in those conversations and may be more or less important to any individual patient. It’s important that we take the time to have those conversations, and that we give patients materials or resources to use, so if they can’t make a choice right now, they can go home, think about it, read about it, learn about it, come back, and continue to have conversations if [the decision is] not clear right away. Shared decision-making isn’t going away in advanced prostate cancer care. The more [treatment] opportunities we have and the more advances we make, the more opportunities we’ll have to match each patient with the right treatment for them.

References

1. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed October 15, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
2. Novartis Pluvicto demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. News release. Novartis. June 2, 2025. Accessed October 15, 2025. https://www.novartis.com/news/media-releases/novartis-pluvictotm-demonstrates-statistically-significant-and-clinically-meaningful-rpfs-benefit-patients-psma-positive-metastatic-hormone-sensitive-prostate-cancer