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Treating Hormone Sensitive Metastatic Prostate Cancer

Insights From: Evan Yu, MD, University of Washington; Ulka Vaishampayan, MD, Barbara Ann Karmanos Cancer Institute ; Neeraj Agarwal, MD, Huntsman Cancer Institute
Published: Sunday, Dec 02, 2018



Transcript: 

Neeraj Agarwal, MD: If you ask me what the difference in biology is between nonmetastatic castrate resistant prostate cancer [CRPC] and metastatic castrate resistant prostate cancer, I don’t think anybody knows. Essentially, the biology may be the same because one is nonmetastatic CRPC and one is metastatic CRPC; it’s a matter of volume of disease. From the hormone sensitive setting to castrate resistant setting, we know that biology changes. In terms of androgen receptor amplification and androgen receptor mutation, we know that disease biology becomes more aggressive from hormone sensitive to the metastatic or castrate resistant setting.

Evan Yu, MD: One of the key events in the life of a patient with prostate cancer is the development or transition from hormone sensitive to castration resistant disease. Hormone sensitive just implies the fact that their disease is still responding to androgen deprivation therapy: standard therapies like Lupron [leuprolide] or other testosterone lowering therapies. Now, castration resistant implies that they’re on such therapies, they have a low castrate testosterone level, their PSA [prostate-specific antigen] is rising, and the disease is potentially getting worse.

The treatment of metastatic hormone sensitive prostate cancer has recently been revolutionized by multiple clinical trials that have led to improved outcomes for our patients. For instance, a few years back the CHAARTED trial and the STAMPEDE trial showed a dramatic survival benefit in adding 6 cycles of docetaxel to patients who had new metastatic hormone sensitive prostate cancer, with the caveat that the CHAARTED trial actually broke patients down into a couple of different subgroups: those with low-volume disease and those with high-volume disease.

High-volume disease was designated as 4 or more bone metastases with at least 1 outside of the axial skeleton, or patients with visceral metastases. If you had lymph node metastases, if all your bone lesions were in the axial skeleton, or if you had a limited number of bone metastases, that would be considered low-volume disease. The key difference is that survival seemed to really be exemplified in the high-volume disease subset. When you followed the low-volume disease subset, there really was no survival benefit with docetaxel.

The other agent that’s also approved in that setting now is abiraterone acetate. That was from the LATITUDE trial and also an arm of the STAMPEDE trial that showed a dramatic survival benefit with the addition of abiraterone acetate. Now, the LATITUDE trial did not break down high-volume or low-volume disease like the CHAARTED trial did with docetaxel, but the thing to keep in mind is that the STAMPEDE trial did have patients who were in the M0 population. That means they didn’t have metastatic disease. If you look at the forest plots of the subgroup analyses, the 95% confidence interval just barely crosses 1, even for the patients with nonmetastatic prostate cancer.

In my practice, I tend to give abiraterone for those with low-volume disease given the fact that there was almost a statistical benefit for those with M0 disease. For high-volume disease, I talk to the patient about comorbidities, costs, financial toxicities, and all these sorts of things and make a decision on abiraterone and docetaxel based on that. I would say it ends up being about a 50/50 split.

Transcript Edited for Clarity 
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Transcript: 

Neeraj Agarwal, MD: If you ask me what the difference in biology is between nonmetastatic castrate resistant prostate cancer [CRPC] and metastatic castrate resistant prostate cancer, I don’t think anybody knows. Essentially, the biology may be the same because one is nonmetastatic CRPC and one is metastatic CRPC; it’s a matter of volume of disease. From the hormone sensitive setting to castrate resistant setting, we know that biology changes. In terms of androgen receptor amplification and androgen receptor mutation, we know that disease biology becomes more aggressive from hormone sensitive to the metastatic or castrate resistant setting.

Evan Yu, MD: One of the key events in the life of a patient with prostate cancer is the development or transition from hormone sensitive to castration resistant disease. Hormone sensitive just implies the fact that their disease is still responding to androgen deprivation therapy: standard therapies like Lupron [leuprolide] or other testosterone lowering therapies. Now, castration resistant implies that they’re on such therapies, they have a low castrate testosterone level, their PSA [prostate-specific antigen] is rising, and the disease is potentially getting worse.

The treatment of metastatic hormone sensitive prostate cancer has recently been revolutionized by multiple clinical trials that have led to improved outcomes for our patients. For instance, a few years back the CHAARTED trial and the STAMPEDE trial showed a dramatic survival benefit in adding 6 cycles of docetaxel to patients who had new metastatic hormone sensitive prostate cancer, with the caveat that the CHAARTED trial actually broke patients down into a couple of different subgroups: those with low-volume disease and those with high-volume disease.

High-volume disease was designated as 4 or more bone metastases with at least 1 outside of the axial skeleton, or patients with visceral metastases. If you had lymph node metastases, if all your bone lesions were in the axial skeleton, or if you had a limited number of bone metastases, that would be considered low-volume disease. The key difference is that survival seemed to really be exemplified in the high-volume disease subset. When you followed the low-volume disease subset, there really was no survival benefit with docetaxel.

The other agent that’s also approved in that setting now is abiraterone acetate. That was from the LATITUDE trial and also an arm of the STAMPEDE trial that showed a dramatic survival benefit with the addition of abiraterone acetate. Now, the LATITUDE trial did not break down high-volume or low-volume disease like the CHAARTED trial did with docetaxel, but the thing to keep in mind is that the STAMPEDE trial did have patients who were in the M0 population. That means they didn’t have metastatic disease. If you look at the forest plots of the subgroup analyses, the 95% confidence interval just barely crosses 1, even for the patients with nonmetastatic prostate cancer.

In my practice, I tend to give abiraterone for those with low-volume disease given the fact that there was almost a statistical benefit for those with M0 disease. For high-volume disease, I talk to the patient about comorbidities, costs, financial toxicities, and all these sorts of things and make a decision on abiraterone and docetaxel based on that. I would say it ends up being about a 50/50 split.

Transcript Edited for Clarity 
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