Of patients who come to my clinic for the first time with mCRPC, some are within the spectrum are those patients who are M0, whereby radiographic evaluation reveals no demonstrable lesions, and therefore they are identified as having M0 CRPC based upon a rising PSA, usually obtained at least 2 times, with elevations from their nadir level and a demonstrated testosterone level of <50 ng/dL.

Most of those cases would likely have a very high Gleason score, with neuroendocrine differentiation, that tend not to respond to androgen ablation alone. Almost all initial metastatic prostate cancer – at least for a certain period of time – responds to hormones, unless you have a lot of neuroendocrine differentiation that doesn’t follow any of the normal hormonal responsive rules.

Just to take a step backward, with respect to presentations of advanced prostate cancer, the 2 big groups we are dealing with are advanced prostate cancer at presentation, or with initial therapy, and then those patients who relapse after therapy. In the United States, in a PSA-screened population, only about 2% of patients present with de novo metastatic disease. Most patients who present with metastatic disease in this country are patients who were thought to have localized disease under one initial therapy and then relapse.

With respect to hormonal-refractory disease, I think we have created this castrate-resistant arena, a lot of it, by taking patients who have biochemical failure after a local therapy and treating them with ADT, having a drop in the PSA, feeling good about it, and then seeing the PSA rise again. The resulting disease tends to fall into this category of M0 CRPC.

We wait for the transition from M0 to M+ CRPC, and that is the point at which all of the new treatments are used. As we are well aware, the longer the cancer is around, the more genetic heterogeneity exists, and the less responsive it is to therapy. And there is movement of the therapies earlier in steps – eg, from post-chemo to pre-chemo, etc. I believe that is where the future is.

I think the treatment considerations here are going to also depend on the disease state, locoregional vs distant metastases, the number of sites, and the biology. This is where these molecular markers such as androgen-receptor splice variant 7 messenger RNA (AR-V7) come in to define the biology. Germ line testing with hormonal-refractory disease has given us some insight into patients who may be candidates for poly ADP ribose polymerase (PARP) inhibitors. For advanced imaging and molecular profiling, disease state, and symptoms, all of these things are taken into account when choosing treatment. I think that, as a result, we are starting to have more precise recommendations based on much better evidence than in the past.