Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Andrology. 2013 May;1(3):505-11. doi: 10.1111/j.2047-2927.2013.00068.x. Epub 2013 Feb 27.
Great advances in tissue androgen analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) have made it possible to evaluate the tissue androgen content from a single needle prostate biopsy specimen. In this study, we investigated if pre-treatment androgen content in prostate biopsy specimens could predict their response to primary androgen deprivation therapy (ADT) and future castration-resistant prostate cancer (CRPC). One-hundred and sixty-five prostate cancer patients who received primary ADT were enrolled. They had received multiple core prostate needle biopsy at diagnosis, and an additional one needle biopsy specimen was obtained for tissue androgen determination using LC-MS/MS. The patients' prostate specific antigen (PSA) values were periodically followed during the treatment and patients were determined to have CRPC when their PSA value increased continuously to 25% above the nadir and a 2.0 ng/mL increase. A significant correlation was found between PSA value decline velocity (PSA half-time) after ADT and pre-ADT tissue androgen content. Twenty-three patients were determined to have CRPC. These CRPC patients had a significantly high concentration of tissue T (p < 0.01) and low concentration of tissue 5α-dihydrotestosterone (DHT) (p < 0.01), resulting in a higher tissue T/DHT ratio (p < 0.001). A multivariate Cox proportional hazard model revealed the pre-ADT tissue T/DHT ratio and Gleason score as independent predictors for CRPC development. By using the two statistically significant variables, the relative risk of CRPC development could be calculated. The results of this study suggest that the evaluation of prostate androgen content in a single needle biopsy specimen may be useful to predict future CRPC development after primary ADT. Further studies are required for the clinical application of T/DHT ratio evaluation.
采用液相色谱-串联质谱（LC-MS/MS）对组织雄激素进行分析的重大进展，使得评估单个前列腺活检标本中的组织雄激素含量成为可能。在这项研究中，我们研究了前列腺活检标本中的预处理雄激素含量是否可以预测其对原发性去势治疗（ADT）的反应和未来的去势抵抗性前列腺癌（CRPC）。纳入了 165 例接受原发性 ADT 的前列腺癌患者。他们在诊断时接受了多次核心前列腺针吸活检，并且使用 LC-MS/MS 从额外的一个针吸活检标本中获得组织雄激素测定。在治疗期间定期随访患者的前列腺特异性抗原（PSA）值，当 PSA 值连续增加到最低点的 25%以上且增加 2.0 ng/mL 时，患者被确定为患有 CRPC。ADT 后 PSA 值下降速度（PSA 半衰期）与预 ADT 组织雄激素含量之间存在显著相关性。23 例患者被确定为患有 CRPC。这些 CRPC 患者的组织 T 浓度明显升高（p < 0.01），组织 5α-二氢睾酮（DHT）浓度降低（p < 0.01），导致组织 T/DHT 比值升高（p < 0.001）。多变量 Cox 比例风险模型显示，ADT 前组织 T/DHT 比值和 Gleason 评分是 CRPC 发展的独立预测因子。通过使用两个具有统计学意义的变量，可以计算出 CRPC 发展的相对风险。这项研究表明，评估单个前列腺活检标本中的前列腺雄激素含量可能有助于预测原发性 ADT 后未来的 CRPC 发展。需要进一步的研究来评估 T/DHT 比值评估的临床应用。
