Performance status is an important factor to consider in a patient with progressive metastatic castration-resistant prostate cancer (mCRPC). However, it’s also important to determine why performance status is poor, says Celestia S. Higano, MD, FACS. Poor performance status can be attributed to comorbidities or to cancer-related symptoms. In the latter case, a gratifying and fairly rapid response to chemotherapy can often be achieved, notes Higano.
At this point, the cumulative myelosuppressive effects of docetaxel and radium-223 are unknown, so they cannot be given together, comments Raoul Concepcion, MD, FACS. Higano agrees, noting that although radium-223 is not myelosuppressive by itself it can be when combined with chemotherapy, which requires dose adjustment. However, radium-223 can safely be given sequentially in a patient who becomes symptomatic after chemotherapy.
Returning to a previous case study of a patient progressing 8 to 12 months after chemotherapy, abiraterone plus prednisone would be a good option, suggests Joseph Renzulli, II, MD, FACS. Enzalutamide would not be an option because the patient has had seizures. Good palliative care services can be invaluable for pain management in this case, continues Renzulli. Cabazitaxel would also be a reasonable choice for this patient, if he did well with docetaxel, adds Petrylak. There are data showing that abiraterone and cabazitaxel can be given together safely at their full dosages.
There are several “right answers” in this case scenario, and the details of the patient’s situation will help to sort out the most appropriate choice, adds Chris Evans, MD, FACS. If the patient had difficulty with docetaxel-related toxicity, abiraterone would be a good choice, he agrees. There is an emerging agent, galeterone that will be evaluated in a phase III trial. Galeterone is a multitargeted oral steroid analogue that works by both androgen receptor modulation and CYP17 inhibition. It appears to be most effective in the patients who are AR-V7-positive, and will be tested in that setting.
After fully discussing the case scenario, the panelists conclude by providing their feedback on a variety of topics. Evans notes that guidelines are very useful for helping to steer treatment selection toward the right and wrong therapies; this can be the starting point to approach a particular patient. Guidelines and clinical trials continue to guide the treatment of each individual patient. However, sometimes the patient sitting in front of you doesn’t fit into a category for which there’s a guideline or trial, which requires the physician to exercise the art of medicine, emphasizes Higano.
Given the enormous amount of data and the different options that are available for patients as they move through their disease states, comments Renzulli, earlier definition of metastatic disease will benefit patients: earlier is better. There is a need to find molecular markers to aid in distinguishing patients, adds Petrylak. AR-V7 is a start, but other markers are necessary to determine whether a patient should go on early chemotherapy or isotopes, and to suggest the best ways to combine agents.