Castration-resistance is defined as a 2 point, or 25%, increase in PSA levels from nadir in patients whose testosterone levels have been reduced below the traditional threshold of 50 ng/dL, explains Stephen J. Freedland, MD. Additionally, in the absence of PSA increases, new onset metastases denote castration resistance.

The term castration-resistant prostate cancer (CRPC) replaced the older term hormone-refractory prostate cancer, since many patients who experience a rise in PSA still remain sensitive to hormonal therapy, notes Freedland. In fact, many therapies are now approved that can be utilization following castration resistance, such as bicalutamide (Casodex) or other second-generation androgen receptor inhibitors.Â

In the absence of radiographic metastases, or M0 disease, there are few approved therapeutics for patients with a rising PSA. At this point, observation or a clinical trial should be considered. However, once patients develop metastases, several therapies become available, notes Raoul S. Concepcion, MD.

In the past, patients with symptoms or visceral metastatic CRPC received treatment with docetaxel, notes David I. Quinn, MD. However, augmenting the blockade of the androgen receptor may still be effective in this setting. This can be accomplished in a variety of ways, either by switching from an LHRH agonist to antagonist, adding bicalutamide, or utilizing one of the newer agents, such as abiraterone acetate or enzalutamide.

In addition to the hormonal strategies, the initiation of immunotherapy with sipuleucel-T has been shown to be most effective in earlier settings, notes Quinn. In this scenario, sipuleucel-T is administered to an asymptomatic or minimally symptomatic patients with CRPC followed by androgen blockade.

When the only option was docetaxel, patients were not followed as closely, since the number of treatments was small. However, now that immunotherapy and second-generation androgen therapies are available, it is more important to detect early-stage CRPC, since earlier treatment lead to better outcomes, Quinn says.