Management of nonmetastatic castration-resistant prostate cancer

The widespread use of prostate-specific antigen (PSA) resulted in stage migration of prostate cancer where androgen deprivation therapy (ADT) is administered for biochemical recurrence in patients following primary treatment. A proportion of these patients progress to a disease state termed nonmetastatic castration-resistant prostate cancer (nmCRPC), with a rising PSA despite ADT and without evidence of metastases on conventional imaging. We will review the treatment options in nmCRPC, especially in light of recent trials showing significant improvement in metastasis-free survival with newer agents.

Historically, nmCRPC patients were followed-up if PSA doubling-time (PSADT) exceeded 10 months. Treatment options for patients with shorter PSADT included hormonal manipulations that often resulted in transient PSA decline. Denosumab was found to delay the onset of bone metastasis but did not impact survival. Recently, phase 3 trials showed that second-generation antiandrogens resulted in a significant delay in metastasis and a trend toward survival improvement in a select group of nmCRPC patients.

The importance of reducing mortality and morbidity associated with metastasis has led to the acceptance of new primary endpoints in the design of trials for nmCRPC and might result in widespread approval of new agents for this disease state.