The Differences Between mCRPC and nmCRPC

Neeraj Agarwal, MD:The hallmarks of castrate-resistant metastatic prostate cancer: It is a disease that is characterized by a painful state. Taking a step back, what is the most common cause of suffering and death in our patients with advanced prostate cancer? Skeletal-related events; bone pain fractures, which requires these patients to go on pain medications; and ultimately, when most of the systemic therapies fail, this is 1 of the major reasons to go on hospice care. So how can we prevent these complications of prostate cancer, which occur during the stage of castrate-resistant metastatic prostate cancer? And these characteristics, these symptoms, differentiate metastatic castrate-resistant prostate cancer from hormone-sensitive or castration-sensitive prostate cancer, or nonmetastatic castrate-resistant prostate cancer.

How do we differentiate between castration-sensitive prostate cancer versus castrate-refractory prostate cancer? As we all know, or as anyone who has seen patients with these cancers knows, the first line of androgen deprivation therapy stops working for these patients in a phase that is characterized by onset of bone pain increasing the size and number of bone metastases. This is basically a painful state. This is castrate-resistant metastatic prostate cancer, as opposed to castration-sensitive prostate cancer, which is still responding extremely well to ongoing therapies.

The most important biological change: As we know, the castration resistance is still driven by the androgen receptor. So androgen receptor amplification [and] androgen receptor mutations remain the most important molecular aberrations, which are the drivers behind castrate-resistant metastatic prostate cancer. We also know of several of the mutations, such as, for the sake of discussion, an increase in the PI3 kinase pathway, C-Met pathway, and many other mutations that may kick in. But I think, as we know, the most common molecular aberration underlying castrate resistance remains androgen receptor amplification or mutations.

Transcript edited for clarity.