Concepcion Details Treatment Decisions for 2 Prostate Cancer Patient Scenarios
Published Online:3:24 PM, Wed November 23, 2016
Raoul Concepcion, MD
In the first case, the patient was a 79-year-old male who was referred to urology with an elevated PSA of 12.9 ng/dl. Prior PSA values had been between 4.0 to 5.0 ng/dl from 2007 to 2011. The patient was an ex-smoker, who smoked 2 packs per day for 35 years. He also had a positive family history of prostate cancer, however, he did not have any voiding symptoms at the time he was referred to urology.
The patient was positive for hypertension, CAD, and COPD, but did not have evidence of metastatic disease at the time of diagnosis.
TARGETED ONCOLOGY: What are the treatment options for this patient?
Concepcion: The gentleman we discussed was an elderly gentleman, 79 years old. He presented with prostate cancer, but because of his advancing age, he was started initially on luteinizing hormone-releasing hormone (LHRH) therapy, and was then lost to follow-up. Then, when he went back to his original urologist, at that point [he was found] to have castration-resistant prostate cancer with metastatic disease. He was elderly, but he was relatively asymptomatic.
Your treatment options now in patients who have metastatic castration-resistant prostate cancer (mCRPC) really do follow certain guidelines—both American Urological Association Allied (AUAA) and National Comprehensive Cancer Network (NCCN). The options for therapy include immunotherapies, which would be sipuleucel-T (Provenge); oral agents, including abiraterone acetate (Zytiga), which is a androgen synthesis inhibitor; an androgen receptor inhibitor, which would include enzalutamide (Xtandi); an alpha emitter radiopharmaceutical, which is radium-223, as well as traditional taxane therapies, which would be docetaxel (Taxotere), and for men who have failed docetaxel, it would be cabazitaxel (Jevtana).
In this particularl gentleman, what the guidelines do not tell us is particularly which agents to use. All the studies for these agents have been monotherapy trials. They were not used in combination. They were not done head to head. We know that in patients who are asymptomatic, who have a good performance status, who have a life expectancy greater than 1 year, what the guidelines might indicate is that that patient might be ideally suited for sipuleucel-T, which again is an autologous immunotherapy.
However, when patients progress beyond that, you have to take a look at the patient’s individual characteristics, you have to take into account all of his comorbidities, his functional status, whether he has heart disease or neurological deficits, does he have a history of seizures, does he have a history of strokes, does he have significant cardiovascular disease, is he symptomatic, and is he having a lot of bone pain, because 90% of people who have metastatic prostate cancer will have bone metastases. So all of those things will come into play when we determine the optimal therapy.
[With] traditional cytotoxic chemotherapy vis-à-vis docetaxel or cabazitaxel, a lot of patients do want to steer away from those because of the side effect profile of those medicines. They’re associated with myelosuppression and significant neuropathies. People, if given the choice between an oral therapy—a pill, like abiraterone acetate or enzalutamide—versus an intravenous cytotoxic chemotherapy, they will pretty much try to go with a pill.
Radium-223, the indication for that drug is for patients with bone metastases who are minimally symptomatic and who have very little soft tissue disease.
In this particular patient, he was elderly, and by the time he had progressed he was already in his mid-80s and he had already failed androgen depravation therapy (ADT), although we continue to treat patients with ADT, and with LHRH analogs, because that continues to be part of the treatment scheme. The best choice for this patient, given his history, was really abiraterone acetate, which is [given] 1000-mg daily, taken with prednisone (Deltasone), 5 mg, BID.
TARGETED ONCOLOGY: What are the next steps? When would you order scans?
Concepcion: Once a patient has started on treatment for mCRPC, the follow-up is somewhat dependent on what agent you use. For abiraterone acetate, because it can cause an element of hepatotoxicity—liver dysfunction—the follow-up for patients on abiraterone is that every 2 weeks for the first 3 months, you have to check liver function, potassium, blood pressure, and basically do a more aggressive monitoring because it can potentially be a hepatotoxic agent. That’s one of the difficulties in monitoring patients with abiraterone acetate.
If you choose enzalutamide therapy, which again, is an oral androgen receptor inhibitor, it doesn’t have the hepatotoxic effects, so the monitoring scheme is a little less intense. It doesn’t require every 2-week monitoring of liver enzymes, as well as potassium.
I think most of us, generally, when we start patients on therapy, we like to get PSAs, testosterone levels, alkaline phosphatase every month, pretty much for the first few months because PSA, although we follow it, is not a great surrogate marker for death. The other problem is that 2 of the therapies, including sipuleucel-T and radium-223, do not necessarily have a profound effect on PSA. Laboratory monitoring is somewhat dependent upon therapy.
In terms of radiographic follow-up, I personally, in my practice, tend to do a lot of what we call sodium fluoride PET CTs about every 6 months, or if a patient comes in with new complaints.
When to change therapies should not be predicated on PSA changes only. As I mentioned before, 2 of the therapies do not result in a reduction of PSA. You might actually see PSAs go up in patients who have been treated with sipuleucel-T or radium-223. I personally believe that the indication to stop a new therapy, add a new therapy, or switch to a new therapy, is really based upon progression radiographically.