PURPOSE The contribution of 11-oxygenated androgens to the progression of lethal prostate cancer (PCa) remains unresolved. We hypothesized that evaluating circulating levels of 11-oxygenated androgens, such as the androgen receptor agonist 11-ketotestosterone (11KT), could serve as a potential predictor of the onset of castration-resistant PCa (CRPC). METHODS We used mass spectrometry to quantify 11-oxygenated androgens in postoperative plasma samples acquired from 145 patients who subsequently received androgen deprivation therapy for biochemical recurrence and achieved castrated testosterone levels. Kaplan-Meier survival analyses and multivariable Cox models were used to investigate relationships between steroids and CRPC. RESULTS Of 145 patients, 31 developed CRPC with a median time to CRPC of 57 months. 11-oxygenated androgens levels were unaffected by androgen deprivation therapy, which stands in contrast to the observed changes in testosterone and other steroids. 11KT was the most abundant androgen but was not linked to clinical features. Kaplan-Meier analysis revealed that 11KT levels above the median of 273 pg/mL were associated with a shorter time to CRPC (P = .03). In multivariable analyses, this was supported with an adjusted HR of 2.17 (95% CI, 0.99-4.71; P = .05). CONCLUSIONS 11KT is a key component of the hormonal profile predictive of earlier onset of CRPC. Enhancing our understanding of the specific role of 11KT in the progression to CRPC could help optimize hormonal therapy for castration-sensitive patients with PCa and CRPC.

中文翻译：

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高 11-酮睾酮与复发性非转移性前列腺癌的去势抵抗时间较短有关。


目的 11-氧合雄激素对致死性前列腺癌 （PCa） 进展的贡献仍未解决。我们假设评估 11-氧合雄激素的循环水平，例如雄激素受体激动剂 11-酮睾酮 （11KT），可以作为去势抵抗性 PCa （CRPC） 发病的潜在预测因子。方法 我们使用质谱法量化 145 例患者术后血浆样本中的 11-含氧雄激素，这些患者随后接受雄激素剥夺治疗以治疗生化复发并达到去势睾酮水平。采用 Kaplan-Meier 生存分析和多变量 Cox 模型研究类固醇与 CRPC 之间的关系。结果 在 145 例患者中，31 例发生 CRPC，中位 CRPC 时间为 57 个月。11-氧合雄激素水平不受雄激素剥夺疗法的影响，这与观察到的睾酮和其他类固醇的变化形成鲜明对比。11KT 是最丰富的雄激素，但与临床特征无关。Kaplan-Meier 分析显示，高于中位数 273 pg/mL 的 11KT 水平与 CRPC 时间较短相关 （P = .03）。在多变量分析中，调整后的 HR 为 2.17 （95% CI，0.99-4.71;P = .05）。结论 11KT 是预测 CRPC 早期发作的激素谱的关键组成部分。增强我们对 11KT 在 CRPC 进展中的特定作用的理解可能有助于优化去势敏感 PCa 和 CRPC 患者的激素治疗。