Concomitant use of enzalutamide and radium-223 as third-line therapy for patients with bone-dominant metastatic castration-resistant prostate cancer (mCRPC) does not improve survival compared with the use of radium-223 alone, according to a recent study.

Mohamed E. Ahmed, MB, BCh, of Mayo Clinic in Rochester, Minnesota, and colleagues studied 51 patients with bone-dominant mCRPC treated with radium-223, an alpha-particle-emitting radiopharmaceutical that selectively targets bone metastases. Of these patients, 32 received radium-223 alone (group A) and 19 received radium-223 concomitantly with the second-generation antiandrogen drug enzalutamide (group B). All patients presented with advanced mCRPC, with 100% of patients having had prior second-generation hormone therapy and 95% of patients also having had prior chemotherapy.

Median overall survival (OS) times were 20.4 months in group A and 17.5 months in group B, a difference that was not statistically significant, Dr Ahmed’s team reported online in Clinical Genitourinary Cancer.

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The only independent risk factors associated with improved OS, in both univariate and multivariate analyses, were a baseline PSA level of less than 30 ng/mL and an ECOG performance status of less than 2. The investigators observed a nearly 4-fold increase in OS as a result of these 2 factors. Median OS was approximately 12.7 months for patients with a baseline PSA of 30 ng/mL or higher compared with 25.3 months among those with a baseline PSA of less than 30 ng/mL. On multivariable analysis, a baseline PSA level less than 30 ng/mL was significantly associated with an 83% decreased risk for death compared with a level of 30 ng/mL or more.

Median OS was approximately 21.5 months for patients with an ECOG performance status of less than 2 compared with 11.9 months for those with an ECOG performance status of 2 or higher. An ECOG performance status of less than 2 was significantly associated with a 75% decreased risk for death compared with an ECOG performance status of 2 or higher.

Dr Ahmed and colleagues said their study suggests criteria that might help clinicians select patients with advanced prostate cancer for radium-223 treatment.

Study limitations include its retrospective design and relatively small sample size.


Ahmed ME, Joshi VB, Badawy M, et al. Radium-223 in the third-line setting in metastatic castrate-resistant prostate cancer (mCRPC): impact of concomitant use of enzalutamide on overall survival and predictors of improved overall survival. Published online January 6, 2021. Clin Genitourin Cancer. doi:10.1016/j.clgc.2020.12.009