Treating castration-resistant prostate cancer that has not spread using new hormonal therapies

This study analyzed the effectiveness and safety of new hormonal therapies (nHTs) in patients with non-metastatic castration-resistant prostate cancer (CRPC). The authors concluded that nHT improved the outcomes of these patients. 

CRPC is an aggressive type of prostate cancer that is resistant to androgen deprivation therapy (ADT). ADT is a hormonal treatment that reduces testosterone levels and limits the growth of prostate cancer cells. In non-metastatic (nm) CRPC, the cancer has not yet spread to distant organs and tissues. However, progressive increases in prostate-specific antigen (PSA; a protein produced by the prostate that increases in prostate cancer and is decreased by treatments) levels while testosterone levels are low, raises concerns.

nHTs such as enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubequa) were recently approved for high-risk nmCRPC cases. These treatments have been shown to improve survival without metastasis in patients with CRPC. However, the benefits of nHTs for overall survival in these patietns remain unclear.

This review analyzed the results of 3 randomized clinical trials and included 4117 patients with high-risk nmCRPC. 2694 patients had received an nHT drug and ongoing ADT. Of these, 806 patients were given apalutamide, 955 patients received darolutamide, and 933 patients were given enzalutamide. The other 1423 patients received a placebo with ongoing ADT. Patients were followed on average for 29 to 52 months.

Patients treated with nHTs had a 68% increased chance of survival metastasis-free compared to placebo. Also, nHTs increased the time until PSA started to increase again by 99.2% compared to placebo. 

A 26% increase in overall survival was seen in patients that received nHT compared to placebo (significant improvement in OS).

Significantly higher rates of adverse effects such as fatigue, dizziness, cardiovascular problems, and fractures occurred with nHT compared to placebo.

This study showed that nHT improved the outcomes of patients with high-risk nmCRPC.

This study analyzed data from only 3 clinical trials. Limited data were available on the quality of life and second-line therapies. Further studies are needed to guide nHT choices for patients.