Does testosterone level predict metastasis-free survival in nmCRPC?

Maintenance serum testosterone levels ≥20 ng/dL do not appear predictive of worse metastasis-free survival (MFS) among men with testosterone <50 ng/dL on first-line therapy of nonmetastatic castration-resistant prostate cancer (nmCRPC) using novel hormonal agents, according to a study. 

“The prognostic value of maintaining testosterone levels <20 ng/dL in patients with nmCRPC is limited, and further treatment intensification is not indicated,” the investigators said.  

This retrospective analysis was conducted based on two phase III trials (SPARTAN and ARAMIS). Patients receiving first-line treatment regimens (androgen deprivation therapy [ADT] plus apalutamide in SPARTAN and ADT plus darolutamide in ARAMIS) were grouped according to their maintenance levels of serum testosterone during treatment: <20 and >20 ng/dL. MFS was the primary endpoint. 

The investigators balanced the baseline characteristics of patients using inverse probability of treatment weighting method. They also examined the influence of maintenance levels of serum testosterone on MFS using Kaplan-Meier analysis, multivariable Cox regression models, and Cox models that included testosterone levels as a time-dependent covariate. 

In Kaplan-Meier analysis, no statistically significant association was observed between serum testosterone levels and MFS in either trial. 

Both multivariable Cox regression models and time-dependent Cox regression models also showed no statistical significance in the relationship between serum testosterone levels and MFS, with <20 ng/dL as reference: multivariable Cox (SPARTAN: hazard ratio [HR], 0.68, 95 percent confidence interval [CI], 0.47–0.98; p<0.05; ARAMIS: HR, 0.83, 95 percent CI, 0.57–1.20; p=0.320) and time-dependent Cox (SPARTAN: HR, 0.84, 95 percent CI, 0.68–1.04; p=0.110; ARAMIS: HR, 1.21, 95 percent CI, 0.71–2.08; p=0.480). 

In addition, similar results were obtained by setting testosterone levels as a continuous variable. 

“The European Association of Urology guidelines and the latest recommendations from the US Prostate Cancer Conference suggest a castration threshold of 20 ng/dL,” the investigators said. “However, the current National Comprehensive Cancer Network and American Urological Association guidelines still recommend a castration standard of 50 ng/dL.”