The percent decline in PSA may predict survival outcomes among men with nonmetastatic castration-resistant prostate cancer (nmCRPC) and rapidly rising PSA treated with androgen deprivation therapy and enzalutamide, according to study findings presented at the virtual 2021 Genitourinary Cancers Symposium.
In a post hoc analysis that included 905 patients with nmCRPC who participated in the phase 3 PROSPER trial and were treated with enzalutamide, Maha H. Hussain, MD, of Northwestern Medicine’s Feinberg School of Medicine in Chicago, and colleagues found that median overall survival (OS) and metastasis-free survival (MFS) increased with increasing depth of PSA decline.
The median OS was 34.6 and 50.0 months for patients with a PSA decline of less than 50% and 50% or higher but less than 90%, respectively. The median MFS for these PSA decline categories was 13.8 and 26.2 months, respectively.
Compared with patients whose PSA level declined less than 50% (reference), patients with a PSA decline of at least 50% but less than 90% had a 50.8% and 63.7% reduced risk for death and metastasis, respectively.
Patients who had a 90% or greater decline in PSA to a nadir of 0.2 ng/mL or higher had a median OS and MFS of 64.0 and 36.6 months, respectively. The median OS and MFS was not reached among patients who had a 90% or greater decline in PSA to a nadir below 0.2 ng/mL.
Compared with the reference group, patients whose PSA declined by 90% or more to a nadir of 0.2 ng/mL or higher had a 73.8% and 82.5% decreased risk for death and metastasis, respectively. Men whose PSA declined by 90% or more to a nadir below 0.2 ng/mL experienced a 90.3% and 94.1% decreased risk for death and metastasis, respectively. All of the differences in outcomes between the subgroups were statistically significantly.
“Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC,” Dr Hussain’s team concluded.
The PROSPER trial enrolled 1401 men with nmCRPC and a PSA level of 2 ng/mL or higher at baseline and a PSA doubling time of 10 months or less. The trial demonstrated that patients treated with enzalutamide had significantly prolonged OS and MFS compared with placebo recipients. Median OS was 67.0 months among the enzalutamide group and 56.3 months among the placebo group.
Disclosure: This clinical trial was supported by Pfizer Inc. and Astellas Pharma, Inc. Please see the original reference for a full list of authors’ disclosures.
Hussain MH, Sternberg CN, Efstathiou E, et al. Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA). Presented at the virtual 2021 Genitourinary Cancers Symposium, February 11 to 13. Abstract 94.