¹⁷⁷Lu-PSMA-617 has significantly impacted the management of metastatic castration-resistant prostate cancer (mCRPC), although challenges persist in optimal patient selection and treatment strategies due to disease heterogeneity. The effective optimization of this therapy requires a multidisciplinary effort between nuclear medicine experts and oncologists on dosing and scheduling.

There are 2 major changes that have transformed the way we manage prostate cancer. The first is the use of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) to diagnose prostate cancer, and the second is that we now have a therapy tied to that imaging: the radioligand therapy ¹⁷⁷Lu-PSMA-617. This has become an important new therapy because, unlike radium-223, it is not dependent on the sites of metastases, which could be in bone and any soft tissue. In the setting of mCRPC, we can now correlate the images with the therapy that is delivered directly to those locations. Since its US Food and Drug Administration (FDA) approval, we have been treating patients with ¹⁷⁷Lu-PSMA-617 both pre- and postchemotherapy.

Overall, we are excited about this first-in-class treatment, but it does not help all patients. Patients taking ¹⁷⁷Lu-PSMA-617 are thus far not cured, and the response rate is not 100%. There are toxicities as well. What this means is that we are still trying to find the best patient population for this therapy. There are features and variables that we do not fully understand because the disease itself is so heterogeneous.

So, who should we be giving ¹⁷⁷Lu-PSMA-617 to? When should we be giving it? Where does it fall in the classic dichotomy for mCRPC (eg, pre- or postchemotherapy)? Finally, what kind of imaging markers are we seeing that would trigger the use of this treatment? Because PSMA PET/CT had only been around for a few years before the FDA approval of ¹⁷⁷Lu-PSMA-617, we are still in the early stages of optimizing treatment based on factors such as dosimetry, schedule, and response. Looking at clinical trials, they do not always give us the granularity that is needed to make clinical decisions about the patients who are in front of us.

That said, the PSMA PET/CT scan gives me a sense of who is more likely to respond based on very simple criteria. For example, a mean standardized uptake value of greater than 10 has become a valuable pragmatic predictor of who is more likely to benefit from ¹⁷⁷Lu-PSMA-617, regardless of the disease state.

I think that for the average busy clinician, the reports need to be simplified in a way that say “yes” or “no” to a certain treatment. If we get to a point where we can say, “This patient is highly unlikely to respond based on these PSMA PET/CT parameters alone,” it would be a huge service. Right now, many PSMA PET/CT reports do not indicate this. Moreover, there is a discrepancy between PET/CT reports that I have seen from some private practices and academic centers. I think that over the next few years, we will reach a point where physicians will have more information to guide ¹⁷⁷Lu-PSMA-617 treatment.

When it comes to dosing and scheduling, we are still learning with ¹⁷⁷Lu-PSMA-617 and with radiopharmaceuticals for prostate cancer in general. Oncologists are not the health care providers who are treating patients with this drug—that is up to our nuclear medicine and/or radiation oncology colleagues. So, it is really important that there is communication about dose and schedule optimization across the treatment team to ensure patient safety and quality of life.