ESMO 2024: Does Lower Serum Testosterone Predict Metastases-Free Survival in nmCRPC Patients Treated with Novel Antiandrogens? a Post-Hoc Analysis of SPARTAN and ARAMIS

(UroToday.com) The 2024 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Xudong Ni discussing whether lower serum testosterone predicts metastases-free survival in nmCRPC patients treated with novel antiandrogens. 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.


This study was a retrospective analysis based on two phase III clinical trials (SPARTAN,1 ARAMIS2). Patients who 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 metastases-free survival. 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.

Baseline characteristics were well balanced between the low testosterone group and the high testosterone group after applying IPTW weights: 

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Kaplan-Meier analysis revealed that serum testosterone maintenance levels were not associated with disease progression in either trial:

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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):

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The results obtained by setting testosterone levels as a continuous variable were similar.

Dr. Ni concluded this presentation by discussing whether lower serum testosterone predicts metastases-free survival in nmCRPC patients treated with novel antiandrogens with the following take-home points:

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

Presented by: Xudong Ni, MD, Fudan University Shanghai Cancer Center, Shanghai, China

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Society of Medical Oncology (ESMO) Annual Meeting, Barcelona, Spain, Fri, Sept 13 – Tues, Sept 17, 2024. 

References:

  1. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
  2. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.