Andrew J. Armstrong, MD, MSc: The main factors that I look at when I’m assessing a patient with mCRPC [metastatic castration-resistant prostate cancer] are their prior therapy exposures, genetic profile, and phenotype: basically, the pattern of spread and the clinical prognostic factors that help you make a decision. Generally, the NCCN [National Comprehensive Cancer Network] guidelines, which we recently updated, can provide a lot of this information. Genetic profiling could be helpful even in the frontline setting. For example, the PROpel and MAGNITUDE studies suggest that if a patient has a BRCA2 mutation, there may be a substantial benefit to the combination of abiraterone plus olaparib or niraparib, pending FDA authorization. But in most patients who are HRD [homologous recombination deficiency] negative, using an AR [androgen receptor] inhibitor as a frontline therapy is the most common practice.

We’re increasingly seeing these therapies move into earlier settings. When a second AR inhibitor isn’t the standard of care and you’re picking a non–cross-resistant drug or something else that may benefit the patients, radium, [lutetium-] PSMA [prostate-specific membrane antigen], docetaxel, and cabazitaxel are good weapons. Molecular profiling can also help. If a patient has had an AR inhibitor and has an HRD mutation, olaparib and rucaparib are available. For a patient who has MSI [microsatellite instability]–high [disease], I’ve seen some of the greatest remissions that I’ve ever seen with pembrolizumab. It would certainly be worth testing for the 3% to 5% of patients who can have an extraordinary response.

Scott Tagawa, MD, MS, FACP: Thankfully for me and the patients I see every day, we have more options today than we did before. That being said, for the average practitioner who sees many types of cancers, it can be complicated. One [clinical pearl] I’d offer is don’t be afraid to ask for help, whether that’s reaching out to a consultant or sending the patient for a second opinion. That’s quite important.

It’s important to recognize that multiple drugs are better than a single drug in the first-line [noncastration] setting. That’s one of the biggest travesties that I see. Our data are a little behind, but there are still too many patients receiving only ADT [androgen deprivation therapy] or ADT plus a nonsteroidal or old-fashioned antiandrogen, such as bicalutamide, in the first-line setting. But at least 2 drugs, and potentially 3, are indicated for most patients.

[It’s also important to] remember clinical trials. As I mentioned, clinical trials are available for every single line of therapy. If you’re in private practice and running out of options, it’s a no-brainer to find out what clinical trials [exist]. But they also exist for earlier lines of therapy, including frontline therapy. Patients as well as physicians can benefit from participation in clinical trials.

Oliver Sartor, MD: I’ve mentioned a few clinical trials and I’d like to emphasize them again. One is the PSMAfore trial, which is looking at patients with metastatic CRPC who have failed a novel hormone, such as apalutamide, darolutamide, enzalutamide, or abiraterone. We also have the SPLASH trial that’s in a similar space. Both of these use PSMA-lutetium. But [another] important trial is PSMAddition, where [we have a] hormone-sensitive patient who’s PSMA-positive and give them novel hormones—ADT-apalutamide, ADT-abiraterone, whatever—[including or excluding] PSMA-lutetium.

Moving forward, we’re going to explore other isotopes. We have isotopes right now with thorium-227 and another trial with actinium-225 that we’re exploring. We have a variety of radiopharmaceutical trials, targeted trials with AR mutations, and some bispecific [antibody] trials, including targeting STEAP1. All of these are of potential interest for those with advanced prostate cancer.

Transcript edited for clarity.