Advances in Metastatic Castration-Sensitive Prostate Cancer - Episode 5

The NCCN and AUA Guidelines for Treating nmCRPC

Neeraj Agarwal, MD:The treatment paradigm of nonmetastatic castration-resistant prostate cancer has gone through a revolution over the last year. We saw the approval of apalutamide, we saw the approval of enzalutamide, and we are going to see a darolutamide approval happening very soon. We have these 3 drugs with level 1 evidence, based on clinical trials with more than 1000 patients in each of these trials. So these were very rigorously conducted clinical trials.

Not surprisingly, these drugs are already a part of the NCCN [National Comprehensive Cancer Network] and AUA [American Urological Association] guidelines. Especially enzalutamide and apalutamide, which are already approved and are mentioned in the guidelines as level 1 evidence.

If we look at these guidelines, there are levels of evidence. This refers to how strongly the panel members of these guidelines feel about these drugs. And without any surprise here, we see that these drugs are endorsed by the NCCN and AUA guidelines for the treatment of nonmetastatic castrate-resistant prostate cancer with level 1 evidence.

What do the guidelines say about using abiraterone plus prednisone for nonmetastatic castrate-resistant prostate cancer? As we know, there has not been a rigorously conducted phase III trial, registration trial, supporting the use of abiraterone with prednisone in this setting. However, there are going to be some patients who may be candidates for this option, for abiraterone, like patients who have had seizures in the past. They’re obviously not eligible for treatment with enzalutamide, for example. So if they’re not eligible for these newer drugs, like enzalutamide and apalutamide, of course we need other options.

Abiraterone doesn’t have the level 1 evidence, category 1 recommendation, for nonmetastatic castrate-resistant prostate cancer. But if I have a patient who’s not eligible for treatment with apalutamide or enzalutamide, I would be very glad to use abiraterone and prednisone.

Do I have a preference for any of the agents, like apalutamide, enzalutamide, or darolutamide, for the treatment of nonmetastatic castrate-resistant prostate cancer? The answer is no, right now. These drugs have not been compared with one another. I agree that these drugs were tested in large phase III trials, and were compared with placebo. But we all know there are caveats. And because they have not been compared with one another, as of today, I cannot say 1 of these drugs is better over another.

I think we need studies comparing these drugs—comparing quality of life, comparing treatment outcomes—to be able to say which drug is better and which should be used. As of now, I think all 3 drugs—apalutamide, enzalutamide, and darolutamide—are considered equal. I don’t have any specific preference for 1 of these right now.

Transcript edited for clarity.