Patients who have high-risk disease to begin with (as defined by cancer grade, prostate-specific antigen [PSA], and tumor volume) are more likely to relapse, and to relapse earlier. They are generally characterized by earlier relapse and usually unfavorable PSA kinetics. The patients who have lower-risk disease who relapse late with favorable kinetics are the ones who either have locoregional recurrence or have tumors that may be metastatic or with favorable biology. This is where positron emission tomography (PET) imaging is identifying these patients. These could be patients who underwent initial therapy. You image them, and you find that they may have a solitary lymph node occurrence. We’ve seen supraclavicular metastases as well as mediastinal metastases – isolated relapses. It’s really defining how we manage these patients. As mentioned earlier, many patients who would have undergone systemic therapy alone are getting a more targeted approach with surgery or stereotactic body radiation (SBRT).

Most patients, when they develop metastatic disease – if they have been followed pretty closely during the transition from androgen sensitive to castration resistant – are going to be asymptomatic. If they have documentation of radiographic disease and they are asymptomatic and M1 CRPC, I am happy to discuss with them the options of sipuleucel-T, and/or starting a novel oral hormonal therapy, either abiraterone acetate or enzalutamide.

We’ve generated some phase 2 data demonstrating very nicely that one can combine sipuleucel-T with either abiraterone acetate or with enzalutamide. But usually, because sipuleucel-T is given over such a short period of time (4-6 weeks), it’s not really a challenge or a concern to start concomitant therapy. If the patient finishes the sipuleucel-T and then is started on a novel oral hormonal therapy [eg, he has bone-predominant disease, and maybe with some small, soft tissue disease but no visceral disease (which is a very common presentation)], I’ll start him on an oral therapy after we review the advantages and disadvantages of the 2 agents. Patients can have very long response duration, in the range of 12 and 24 months, or sometimes it is much shorter.

If while on treatment the PSA starts to rise and the patient is not necessarily showing any radiographic progression of disease and no change in symptomatology, I will maintain that therapy, and I rarely will make a switch – unless I am looking at a clinical trial. I also inform my patients that the use of all of these therapies is something that I want them to consider receiving over their cancer care journey. If there are new lesions and/or any change in symptomatology, then I will be very quick to switch to or add another therapy. I am not a proponent of switching from abiraterone to enzalutamide or enzalutamide to abiraterone, unless it’s part of a clinical study. In a real-world practice, I’d much rather consider radium-223, if, indeed, the patient is having some new symptomatology related to his bone disease, and there’s a good window of opportunity in my judgment to complete the recommended 5-6 cycles of radium-223.

Once patients present with symptoms due to advanced prostate cancer, all currently approved first-line mCRPC agents can be used, except for sipuleucel-T. There is a spectrum of how patients present, however, and in the modern world, patients are not really presenting as often with the prominent symptomatic disease they might have had in the past. That’s because, hopefully, if men have been treated for local disease and then they develop metastatic disease, and then they proceed to a castrate-resistant space, they’re being followed fairly closely. Their symptom evolution may not present as it might have decades ago, when patients would present more often with spinal cord compression or pathologic hip fractures. So, I think that, beyond minimal disease, with sipuleucel-T being one of those agents that you might want to think about first, everything else after that – unless you are really severely symptomatic – really comes down to whether the inclination is to use abiraterone or enzalutamide or radium-223 or docetaxel or other agents. It’s really up to the individual clinician and his or her comfort level, in conjunction with the patient and individual characteristics of the patient.

We published a paper recently in Urology on the consensus from RADAR II, where we looked at therapeutic layering, examining some of the principles involved in layering on newer agents. We’ve got new drugs that are all different. The idea of putting them together is challenging, but it’s also exciting.