Maha Hussain, MD, FACP, FASCO

Question 1. What should be the basis for starting non-metastatic CRPC (nmCRPC) patients on one of the novel anti-androgens?

Answer
The critical part is determining who should receive them. There are 2 agents that are FDA approved for non-metastatic castration-resistant disease, apalutamide and enzalutamide. Multiple factors come into play, including PSA doubling time, the overall health of the patient, and the potential risk vs benefits potential. For someone who has a PSA doubling time of say, 2 years and has multiple significant comorbidities, I don’t think there is an urgent rush to treat. That’s different from the patient who has a short PSA doubling time. That’s where prescribing the medications preemptively might be better as opposed to waiting.

Question 2. What would you advise urologists regarding the management of adverse effects that impair QOL?

Answer
It’s not just about looking at lab results and PSA, but also having face-to-face discussions with patients and evaluating patients to better assess the cause of the side effects they are experiencing and manage accordingly. If someone develops a seizure, the drug should be stopped. If somebody has a fall that appears to be related to treatment, treatment should be stopped or switched. Issues such as fatigue and worsening hot flashes are something the urologist, the physician managing the patient, or nurse practitioner can manage. If they feel uncomfortable managing it, they should engage the palliative/symptom management team to help with managing symptoms.

Question 3. Who should NOT be treated with these medications?

Answer
When we give a treatment, we give it not because we can but because we should. Consequently, anyone who has significant comorbidities such that the risk from the treatment outweighs the benefits, or, because of age or other health factors, have a very short life span might not be candidates for treatment. These men do not die overnight from cancer. So anyone who has significant disease where the estimated survival because of that disease is short, then adding more toxicity from treatment is not necessary. It’s a balancing of risks and benefits overall.

Question 4. When men with nmCRPC are placed on one of the novel anti-androgens, what do you think should be the follow-up protocol?

Answer
There really is no general evidence-based guidelines in this setting. I usually see the patient about a month after he started the medication to evaluate tolerance, assess side effects, check chemistries. I am very cognizant of the cognitive effects of these treatments, and implement early intervention and/or evaluation by the neuro-cognitive team. Follow-up visits are scheduled based on the overall condition and adjust frequency accordingly. Generally, if all is well, we do a 3-month visit. For patients I am more concerned about because of comorbidities, drug interactions, and other issues, I will monitor them more frequently. Imaging is done at baseline and periodically based on symptoms or laboratory findings. I generally order conventional scans—bone scans and CT scans, if negative then I do order Axumin PET scan.

Question 5. If metastatic disease develops, what would be the next step in treatment?

Answer
It depends on what the patient has received and what kind of health they’re in and other factors. Certainly, other second-generation anti-androgen therapy is appropriate. For example, if somebody was on apalutamide, they could switch to abiraterone/prednisone or enzalutamide. Docetaxel can also be considered. If the patient has bone only metastases, then radium-223 is a consideration. Clinical trials are a critical option always. This all has to do with the case scenario, and the nature of the disease relapse. Decisions regarding therapy should take into account disease extent and biology, patient’s general health and safety considerations, medical appropriateness, and patient’s wishes.