The Evolving Treatment Landscape of Metastatic Castration-Resistant Prostate Cancer - Episode 9

Metastatic CRPC: Considerations for Radiotherapy

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Oliver Sartor, MD, considers the respective roles of Lu-PSMA-617 and radium-223 as radiotherapy in the setting of mCRPC.


Oliver Sartor, MD: We need to talk a little about history in order to understand how we got to where we are today. I’m going to take you way back to the 1990s, when the first radiopharmaceuticals were FDA [Food and Drug Administration] approved. These were things like strontium-89 and samarium-153. These are bone-targeted agents that could have some palliative effects, but they didn’t prolong survival.

The first radiopharmaceutical to prolong survival in prostate cancer was radium-223. Radium-223 targets bony osteoblastic lesions but doesn’t target any other lesions. It doesn’t change the PSA [prostate-specific antigen] very much. Nevertheless, in a prospective randomized trial called the ALSYMPCA trial, it was standard of care plus or minus the radium-223 that demonstrated that radium-223 prolonged survival. That was a very important finding.

Now we have PSMA [prostate-specific membrane antigen]-617–lutetium-177, which also has a prolongation in survival. But this targets all the PSMA PET [positron emission tomography]–positive lesions and we’re not targeting the PSMA PET–negative lesions. We’ve talked about that before. The radiopharmaceuticals, which I like to refer to as molecularly targeted radiation, play an important role because we can deliver the radiation so precisely. If you look at the scans that we can do after PSMA-lutetium treatment, with something called a SPECT [single-photon emission computerized tomography] scan, we can look at the distribution of where the PSMA-lutetium has gone and we see very precise delineation to PSMA PET–positive lesions, and we aren’t radiating areas of the body that aren’t PSMA PET–positive.

Having said that, I want to remind people that the parotids and salivary glands in the submandibular region are PSMA PET–positive and are going to receive some radiation too, hence the dry mouth. But overall, PSMA-lutetium is extremely well tolerated, and it’s this molecularly targeted radiation that provides the advantage. It isn’t the first to prolong survival. Radium-223 was the first. Radium-223 can still play a role for those who have bone metastatic disease within the context of the approvals that the FDA has given. But PSMA-lutetium will have a larger role because it incorporates about 87% of the patients who were treated in the VISION trial, at least by PSMA PET criteria. I’m looking forward to gaining a lot more experience with PSMA-lutetium after the FDA approval. Patients will be the beneficiaries.

There are variety of barriers that could be present. Let’s talk about several of them. No. 1, it requires a PSMA PET scan. PSMA PET scans are relatively new and there can be some reimbursement challenges with them. I’ve had to be on the phone with the insurance company saying, “This guy needs a PSMA PET scan in order to qualify him for the therapy.” The people I’m talking with on the phone aren’t always the brightest ones on the block. They’re going to say, “PET scan? We don’t approve FDG [fluorodeoxyglucose] PETs for these type of patients.” I’ll say, “No, I need a PSMA PET.” They’ll say “Oh, what is that one?” We’re still worried about the PSMA PET learning curve that the insurance companies have to endorse because quite frankly we need that PSMA PET in order to get the patient onto therapy.

No. 2, it requires an authorized user. An authorized user isn’t a medical oncologist like me. It’s typically going to be someone with training in nuclear medicine or radiation oncology. The authorized user may not be the one who’s really treating the patient. In my clinic, I follow the patients. If I want to refer the patient for PSMA-lutetium, I need to talk with my radiation oncologist. In other centers, we might talk to the nuclear medicine doctor. But that involves a handoff, so it takes a multidisciplinary team in order to optimize this therapy and get it to patients. We have 2 in our multidisciplinary teams, but not everyone has that, so they might not have somebody you can call. They might say, “I’m not familiar with that,” or “I’m not licensed for that,” or “I’m not familiar enough in order to be able to implement that in my clinics.”

You need to form these teams so that you can work together to provide this type of therapy for your patients. One clinician—a medical oncologist like myself or maybe a urologist who works with advanced patients—is going to be treating the patient all the way through. Then the referral is going to occur to that nuclear medicine or radiation oncology doctor who’s the authorized user to administer the PSMA-lutetium therapy.

In addition to those barriers, we’re also talking about selling ripe tomatoes, if you will. We have about a 7-day half-life. This isn’t a drug that sits on the shelf and is ready when you’re ready to take it off the shelf. You have to order it, it has to arrive, and if the patient doesn’t arrive at the same time, the dose may go bad because it’s only good for 7 days. If the radioactivity decays, then you don’t have sufficient dose to give to the patient. All of these represent challenges. We have authorized users, isotopes that have a limited half-life, multidisciplinary teams, and PSMA PET scans. Not everything is perfect, but it’s going to get better over time. Those are some of the barriers that I see today.

In addition to bringing in the radiation oncologist or nuclear medicine doctor and having a talk before the patients are treated, you also need to engage with radiation safety and anybody involved with the shipping and handling of radioactivity. It takes a team in order to do it together. It takes some planning. But I’ll simply say this: the patients are the beneficiaries, and if we’re able to get agents such as PSMA-lutetium to our patients, they will benefit. That’s why we need to do it. Not for us, but for the patients. These are solvable issues.

Transcript edited for clarity.