1634P - Does lower serum testosterone predict metastases-free survival in nmCRPC patients treated with novel antiandrogens? A post-hoc analysis of SPARTAN and ARAMIS

Background

The EAU guidelines and the latest recommendations from the US Prostate Cancer Conference suggest a castration threshold of 20 ng/dl. However, the current NCCN and AUA guidelines still recommend a castration standard of 50 ng/dl. It remains unknown whether there is a relationship between maintaining lower testosterone levels and the prognosis of non-metastatic CRPC patients.

Methods

We conducted a retrospective analysis based on two phase III clinical trials (SPARTAN, ARAMIS). Patients received the currently recommended first-line treatment regimens (ADT+apalutamide or ADT+darolutamide) were classified into two groups according to their maintenance levels of serum testosterone during treatment: below 20 ng/dl and above 20 ng/dl. The study endpoint was MFS. IPTW method was employed to balance patients’ baseline characteristics. Kaplan-Meier analysis, multivariable Cox regression models, and Cox models that included testosterone levels as a time-dependent covariate were utilized to investigate the influence of maintenance levels of serum testosterone on disease progression.

Results

Baseline characteristics were well balanced between the low testosterone group and the high testosterone group after applying IPTW weights. Kaplan-Meier analysis revealed that serum testosterone maintenance levels were not associated with disease progression in either trial. In both multivariable Cox regression models and time-dependent Cox regression models, serum testosterone maintenance levels remained unrelated to disease progression, using below 20 ng/dl as the reference group (multivariable Cox: SPARTAN HR, 0.67 [95% CI, 0.44-0.99; P < 0.05], ARAMIS HR, 0.83 [95% CI, 0.57-1.23; P = 0.362]; time-dependent Cox: SPARTAN HR, 0.85 [95% CI, 0.60-1.21; P = 0.365], ARAMIS HR, 0.77 [95% CI, 0.58-1.17; P = 0.222]). The results obtained by setting testosterone levels as a continuous variable were similar.

Conclusions

Among men all with testosterone <50 ng/ml, maintenance serum testosterone levels were not associated with disease progression in the first-line management of nmCRPC with NHTs. The prognostic value of maintaining testosterone levels in patients with nmCRPC is limited.

Clinical trial identification

NCT01946204, NCT02200614.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.