Non-metastatic castration resistant prostate cancer: a review of current and emerging medical therapies

Background Non-metastatic castration resistant prostate cancer (M0CRPC) is a heterogenous disease state affecting an estimated 100,000 men in the United States. Development of more sensitive modalities for detection of metastasis has altered the landscape of advanced prostate cancer, but M0CRPC has remained a condition that previously lacked FDA-approved treatment. The emerging data on new generation Androgen Receptor (AR) pathway inhibitors should address this gap in the management of such patients. Methods We reviewed and summarized the current literature for the definition, diagnosis and treatment of M0CRPC. We highlight the results of recent Phase III trials that show significant impact on the outcomes of M0CRPC. Results Androgen deprivation therapy remains the foundation of therapy for M0CRPC. Recently published Phase III trials provided data on improved progression free survival when ADT is augmented with newer AR pathway inhibitors. The SPARTAN trial showed that metastasis-free survival (MFS) for patients treated with apalutamide plus ADT is 40.5 months compared to 16.2 months for patients who received standard ADT plus placebo, a 72% reduction in the risk of distant metastasis or death in apalutamide plus ADT compared to ADT plus placebo. The PROSPER trial demonstrated that MFS for patients treated with enzalutamide plus ADT was 36.6 months compared to 14.7 months for patients who received standard ADT only indicating a 71% reduction in the risk of developing metastatic CRPC or death compared to ADT alone. The ARAMIS trial on darolutamide, another AR pathway inhibitor, is also ongoing, and can potentially be another fitting option for M0CRPC. Conclusion The recent Phase III trials SPARTAN and PROPSER demonstrate effective treatment options for the M0CRPC disease state that has historically lacked treatment from high level evidence. In particular, an FDA-approved treatment, Apalutamide, can finally be offered for M0CRPC patients. The newer AR pathway inhibitors should provide a basis for further investigation into treatments for M0CRPC.