Expert Perspectives on Advanced/Metastatic Prostate Cancer

EP. 1A: Treatment Overview: Metastatic Hormone-sensitive or Castration-resistant Prostate Cancer

In the first interview of the series, Judd W. Moul, MD, provides an overview of the management of mHSPC and mCRPC including key considerations in the use of the androgen deprivation therapy leuprolide with or without novel hormone therapy or chemotherapy.


Metastatic prostate cancer has unfortunately become more common over the last several years—and in addition to being more common, the death rates from advanced prostate cancer are going up.

When a patient presents with metastatic prostate cancer, [which] is called hormone-sensitive M1 or metastatic prostate cancer, the first thing we do is try to risk-assess that patient to determine how severe his cancer is. We try to determine if it’s a low-volume or a high-volume metastatic prostate cancer, because the treatment approaches will vary.

The baseline treatment, the backbone treatment, for all patients who present with hormone-sensitive metastatic prostate cancer is traditional ADT. The term traditional ADT means a shot, a pill, a combination shot or pill, or even removal of the testicles.

The injections or shots would be a drug such as leuprolide acetate, which [has been a] common treatment for advanced prostate cancer [for a] long time. It has a number of different brands and slightly different formulations. Or, instead of leuprolide acetate, it could be a drug called degarelix, which is a GnRH [gonadotropin-releasing hormone] pure antagonist that could be used, and there are advantages and disadvantages [with each approach]. Most recently [added to our options] is an oral agent called relugolix, which does the same essential thing as the degarelix injection. Finally, if patients did not want to take one of these injections periodically or did not want to take the daily relugolix pill, they could have their testicles removed, which is called a orchiectomy or castration.

Traditional ADT, such as leuprolide acetate, degarelix, or relugolix, will form the backbone treatment for advanced prostate cancer. Over the last 5 to 7 years, research has clearly shown that adding one of these novel hormonal therapies or adding docetaxel chemotherapy definitely improves survival—no question about it. Virtually all patients who present with metastatic disease, who present with hormone-sensitive M1 or metastatic prostate cancer, should receive something else with the traditional ADT. There are currently 4 FDA-approved options [to be added to the ADT]: oral enzalutamide; oral apalutamide ADT or oral hormonal therapy ; abiraterone acetate plus low-dose prednisone; or docetaxel chemotherapy given every 3 weeks for a course of 6 cycles.

The [hormone therapy] pills—enzalutamide, apalutamide, or abiraterone acetate—are all effective whether the patient has low-volume or high-volume metastatic disease, so they could be used in any patient. However, the effectiveness of docetaxel chemotherapy has been proven only in high-volume metastatic disease. So, as a urologist, the first thing I look at is whether my patient has low-volume or high-volume metastatic disease.

So far, we’ve been talking about hormone-sensitive metastatic prostate cancer. Eventually, the vast majority of these patients progress to castration-resistant disease, meaning their disease is getting worse despite [the treatments] we just talked about. Sometimes, these [same] oral agents are used in the castrate-resistant setting. Let’s say, for instance, the patient had previously received docetaxel; next, he may go onto one of the oral therapies. But if a patient had already received one of the oral therapies, then perhaps we would go on to chemotherapy next, because we’ve learned that these novel hormonal therapies are great as first-line [treatments], but once a patient starts to progress after having been on one of these oral agents for several years, [if you] add the second oral agent, you usually don’t get as much bang for the buck.

What we’ve seen in the last 7 years is that using ADT [alone] for metastatic prostate cancer is not enough. Even though leuprolide acetate, degarelix, [and the newest], relugolix, [have been] game changers, those treatments alone are not sufficient for the typical patient presenting with metastatic prostate cancer. They need to add one of the novel hormonal agents—enzalutamide, apalutamide, or abiraterone acetate—or docetaxel chemotherapy. We know that adding those definitely makes a difference. The problem is, data still show that up to 50% of our patients in the United States who present with metastatic prostate cancer do not get this effective therapy. They’re getting just ADT alone and [are] not getting the benefit of one of these additional agents that we know clearly improve survival. In my opinion, the greatest unmet need is having our urologists and medical oncologists who work in the field of advanced prostate cancer do a better job of getting patients on this dual therapy: ADT plus either one of these novel oral agents or 6 cycles of chemotherapy.

Transcript has been edited for clarity.