Answer: This is a patient who underwent radical prostatectomy 10 years earlier for Gleason 5 prostate cancer. He was followed for 3 or 4 years, during which time his PSA was acceptable and he stopped follow-up. Now, 5 years later, he is experiencing pain and has a PSA of 15 ng/mL. The first thing to do is obtain a scan to determine if the scan matches his complaint. In this case, the CT scan confirms metastasis to the sacroiliac joint.
Let’s walk through different scenarios in order to illustrate the decision-making process. A key issue is what happened after the patient had his radical prostatectomy. If he has a PSA rise post–radical prostatectomy, then the first thing to consider is salvage radiation. This is only appropriate for patients with very low PSAs (<2.0 ng/mL) and no metastatic disease. In this patient, however, he has metastatic disease, so salvage radiation is not appropriate.
If he has not had androgen deprivation therapy, then the first thing we would want to do is consider androgen deprivation [Figure 1]. This would typically include an LHRH analog, such as leuprolide acetate, goserelin acetate, or triptorelin pamoate; we may decide to add an anti-androgen, such as bicalutamide. This approach generally works well, as the androgen deprivation relieves pain and results in disease control that may last up to 5 years.1
Now, another scenario is that disease recurrence was detected during follow-up and he received salvage radiation therapy. However, salvage radiation therapy failed and the patient went on to have a slowly rising PSA that was treated with androgen deprivation. After an initial response that lasted 5 years, the patient progressed to a PSA of 15 ng/mL and the metastatic disease was noted. In this scenario, the patient received hormonal therapy. So now we have a patient with metastatic castration-resistant prostate cancer (CRPC). We would determine our next treatment option based on the extent of metastatic disease and symptoms.
If the patient is significantly symptomatic, then we would first consider external beam radiation to the painful area. If you radiate the lesion, excellent palliation is possible 80% to 90% of the time.2,3 Another option for symptomatic patients who do not respond to radiation would, in fact, be chemotherapy—especially for those with castrate-resistant, multifocal metastatic disease.4-8 Trial outcomes confirm the survival and palliative benefits of chemotherapy with docetaxel; docetaxel/prednisone remains the first-line chemotherapy of choice for patients with CRPC.1
If the patient has asymptomatic or minimally symptomatic metastatic CRPC (ie, serum testosterone <50 ng/dL), then we can consider sipuleucel-T. Another consideration would be to add an anti-androgen, such as nilutamide in combination with sipuleucel-T.9
Another facet of this treatment paradigm is where to place newer hormonal agents like abiraterone acetate, which has recently completed phase 3 testing within the chemotherapy-naïve metastatic CRPC setting.10 In an interim analysis, abiraterone was associated with a statistically significant improvement in radiographic progression-free survival (rPFS) and a strong trend for increased overall survival (OS), with a hazard ratio of 0.75. Even though this study did not meet its prespecified OS endpoint, should the FDA approve this agent, we’d have a new opportunity to treat patients with an effective non-chemotherapeutic, non–sipuleucel-T strategy in this situation.