The Truth About the Treatment of Non-metastatic Castrate Resistant Prostate Cancer

There is a sad truth about the current state of affairs for the treatment of non-metastatic castration-resistant prostate cancer. Our treatments can best be described as being antiquated. 

The available treatments include ketoconazole.  Ketoconazole (Keto) turns off the adrenal glands and reduces one source of androgens, but it has never been approved for prostate cancer. Keyto is an old-fashioned antifungal medication. We also can use estrogens.  Estrogens are given those by using either a patch or by mouth.  Estrogens can cause blood clots and breast enlargement and tenderness, so men don’t like them.  They are also hard to regulate when administered by using patches.  

We also have first-generation androgen receptor antagonists such as bicalutamide, flutamide, Nilutamide, Lupron, etc. The cancer almost always becomes resistant to those when it up regulates its androgen receptor. 

Sometimes, medication strategies involve double upping on some of those agents or rotating through them trying to get some effect. But there isn’t data showig that they help people live longer or that they increase the time to the development of metastatic disease. 

Let’s be honest, we are not treating the cancer, we are treating the PSA.   If we really want to be honest we also have to admit we aren’t even treating the PSA very successfully.

We also use AR-targeted therapies to block the actions of the androgens that are still being produced.  When we turn off the production of androgens from the testicles, we’re only blocking about 90% of androgens.  The cancer itself can produce some androgens, as can the adrenal glands. So, the rationale is to block the actions of those androgens by making them unable to bind to the androgen receptor. 

GnRH (gonadotropin-releasing hormone) agonists are those drugs that don’t have the testosterone flare. Most of what we use, such as Lupron (leuprolide), Eligard (leuprolide), or Zoladex (goserelin), are LHRH or GnRH antagonists. These drugs all cause an initial flare in the testosterone before they block it.  This flare can have serious consequences, especially for men with aggressive and progressed prostate cancer.  

There is a very new treatment option which does begin to change this paradigm, apalutamide (Erleada).  Apalutamide does delay the first onset of the development of confirmed metastatic prostate cancer in men who are castrate resistant, but do not have confirmed metastatic disease.  Additionally, preliminary data does show that early use of Xtandi as a similar effect of delaying the development of metastatic disease

Despite the recent FDA approval of Erleada, there is a substantial unmet need in non-metastatic castration resistant prostate cancer. 

Prostate cancer becomes symptomatic and deadly only when it becomes metastatic. Before that in the non-metastatic space, we were only treating a man’s PSA, which is just a lab result. The approval of apalutamide and what will hopefully be the near-term approval of the earlier use of Xtandi are an essential beginning. However, these are just a beginning and do not rise to the level of solving a critical problem.  

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs.  He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.