雄激素抑制和前列腺放疗后的睾酮恢复（TRANSPORT）：来自前列腺癌随机试验荟萃分析（MARCAP）联盟的五项随机试验的汇总分析。

Testosterone Recovery Following Androgen Suppression and Prostate Radiotherapy (TRANSPORT): A Pooled Analysis of Five Randomized Trials from the Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium.

作者信息

Ong Wee Loon, Romero Tahmineh, Roy Soumyajit, Nikitas John, Joseph David, Zapatero Almudena, Malone Shawn, Morgan Scott C, Steinberg Michael L, Valle Luca F, Zaorsky Nicholas G, Martin Ma Ting, Rettig Matthew B, Nickols Nicholas, Jiang Tommy, Reiter Robert E, Eleswarapu Sriram V, Maldonado Xavier, Sun Yilun, Nguyen Paul L, Millar Jeremy L, Martin Jarad M, Spratt Daniel E, Kishan Amar U

机构信息

Alfred Health Radiation Oncology, Monash University, Melbourne, Australia.

Division of General Internal Medicine and Health Services Research, University of California-Los Angeles, Los Angeles, CA, USA.

出版信息

Eur Urol. 2025 Jan;87(1):49-57. doi: 10.1016/j.eururo.2024.09.009. Epub 2024 Sep 20.

DOI:10.1016/j.eururo.2024.09.009

PMID:39304428

Abstract

BACKGROUND AND OBJECTIVE

Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists varies widely. We evaluate TR kinetics and the oncological impact of an effective castration period in patients receiving definitive radiotherapy and ADT for prostate cancer.

METHODS

We obtained individual patient data from randomized controlled trials of radiotherapy with ADT and prospectively collected serial testosterone data from the MARCAP Consortium. We estimated the times to noncastrate TR (>1.7 nmol/l) and nonhypogonadal TR (>8.0 nmol/l) were estimated for each prescribed ADT duration, and developed corresponding nomograms. The association between effective castration period and metastasis-free survival (MFS) for any given ADT duration was evaluated via multivariable Cox regression. We conducted cubic spline analyses to assess nonlinear associations.

KEY FINDINGS AND LIMITATIONS

We included 1444 men from five trials in the analysis, of whom 115 received 4 mo, 880 received 6 mo, 353 received 18 mo, 36 received 28 mo, and 60 received 36 mo of ADT. Times to noncastrate TR and to nonhypogonadal TR varied considerably by ADT duration. Higher baseline testosterone and lower age were associated with a higher likelihood of TR (p < 0.001 for both). Effective castration period was not linearly associated with MFS for any ADT duration on Cox regression. Cubic spline analysis revealed that the optimal effective castration period for an MFS benefit was 10.6 mo for men who received 6 mo of ADT and 18 mo for men who received 18 mo of ADT.

CONCLUSIONS AND CLINICAL IMPLICATIONS

Time to TR varies according to the ADT duration, baseline testosterone, and age. The relationship between effective castration period and MFS may be nonlinear, with a longer effective castration period being helpful for men receiving 6 mo of ADT.

摘要

背景与目的

使用促性腺激素释放激素激动剂进行雄激素剥夺治疗（ADT）后，睾酮恢复时间（TR）差异很大。我们评估接受前列腺癌根治性放疗和ADT患者的TR动力学以及有效去势期对肿瘤学的影响。

方法

我们从放疗联合ADT的随机对照试验中获取个体患者数据，并前瞻性收集来自MARCAP联盟的系列睾酮数据。针对每个规定的ADT持续时间，估计达到非去势TR（>1.7 nmol/l）和非性腺功能减退TR（>8.0 nmol/l）的时间，并绘制相应的列线图。通过多变量Cox回归评估任何给定ADT持续时间下有效去势期与无转移生存期（MFS）之间的关联。我们进行三次样条分析以评估非线性关联。

主要发现与局限性

我们在分析中纳入了来自五项试验的1444名男性，其中115名接受4个月的ADT，880名接受6个月的ADT，353名接受18个月的ADT，36名接受2个月的ADT，60名接受36个月的ADT。达到非去势TR和非性腺功能减退TR的时间因ADT持续时间而异。较高的基线睾酮水平和较低的年龄与TR可能性较高相关（两者p均<0.001）。在Cox回归中，任何ADT持续时间下有效去势期与MFS均无线性关联。三次样条分析显示，对于接受6个月ADT的男性，MFS获益的最佳有效去势期为10.6个月；对于接受18个月ADT的男性，最佳有效去势期为18个月。