de la Taille Alexandre, Martínez-Piñeiro Luis, Cabri Patrick, Houchard Aude, Schalken Jack
INSERM U955 Eq07, Department of Urology, CHU Henri Mondor Assistance Publique des Hopitaux de Paris, Créteil, France.
Urology Unit, Infanta Sofía University Hospital, Madrid, Spain.
BJU Int. 2017 Jan;119(1):74-81. doi: 10.1111/bju.13455. Epub 2016 Mar 23.
To assess time to progression to castrate-resistant prostate cancer (CRPC) and factors influencing longer-term outcomes in patients receiving androgen-deprivation therapy (ADT) in an extension to the Triptocare study (NCT01020448). This is pertinent as the Triptocare study did not show that urinary prostate cancer antigen-3 (PCA3) score was a reliable marker of cancer stage in advanced prostate cancer and was not useful for assessing response 6 months after initiation of ADT with triptorelin 22.5 mg.
An international, multicentre, non-interventional, observational, longitudinal, prospective study involving patients from the Triptocare study. CRPC status of patients was collected for up to 3 years from ADT initiation. Patient treatment and assessments were at the investigator's discretion. Co-primary endpoints were rate of CRPC at 3 years after initiating ADT and the median time to CRPC. An exploratory endpoint was the association of Triptocare baseline variables (including TMPRSS2-ERG and PCA3 scores) and PCA3 score at Triptocare last value available with CRPC onset.
Of the 325 patients in the Triptocare study safety population, 180 patients were enrolled in the Triptocare LT study (102 received continuous and 78 received intermittent ADT). CRPC rates at 3 years were 24/102 (23.5%) and 6/78 (7.7%) patients in the continuous and intermittent ADT groups, respectively. The median time to CRPC was not reached for either group. PCA3 score status at baseline was the only variable associated with a higher risk of progression to CRPC in both the intermittent and continuous ADT groups; compared with a baseline PCA3 score of ≥35, a PCA3 score below the level of quantification had a hazard ratio (HR) of 20.04 ([95% confidence interval (CI) 2.71-148.34] and a HR of 9.44 [95% CI 2.39-37.27], respectively). Baseline metastatic disease and testosterone level were additionally associated with progression to CRPC in the continuous ADT population (HR 5.20, 95% CI 1.68-16.06 and HR 0.995, 95% CI 0.991-0.999, respectively).
In men with locally advanced or metastatic prostate cancer, a PCA3 score of ≥35 at the time of initiating ADT may predict a lower risk of developing CRPC in the following 3 years.
在Triptocare研究（NCT01020448）的一项扩展研究中，评估接受雄激素剥夺治疗（ADT）的患者进展为去势抵抗性前列腺癌（CRPC）的时间以及影响长期预后的因素。这一点很重要，因为Triptocare研究并未表明尿前列腺癌抗原3（PCA3）评分是晚期前列腺癌癌症分期的可靠标志物，并且对于评估使用22.5 mg曲普瑞林启动ADT 6个月后的反应并无用处。
一项国际性、多中心、非干预性、观察性、纵向、前瞻性研究，纳入来自Triptocare研究的患者。从ADT开始起收集患者长达3年的CRPC状态。患者的治疗和评估由研究者自行决定。共同主要终点为启动ADT后3年时的CRPC发生率以及至CRPC的中位时间。一个探索性终点是Triptocare基线变量（包括TMPRSS2-ERG和PCA3评分）以及Triptocare最后可用值时的PCA3评分与CRPC发病的关联。
在Triptocare研究安全人群的325例患者中，180例患者纳入了Triptocare LT研究（102例接受持续ADT，78例接受间歇ADT）。持续和间歇ADT组3年时的CRPC发生率分别为24/102（23.5%）和6/78（7.7%）。两组均未达到至CRPC的中位时间。基线时的PCA3评分状态是间歇和持续ADT组中与进展为CRPC风险较高相关的唯一变量；与基线PCA3评分≥35相比，低于定量水平的PCA3评分的风险比（HR）分别为20.04（[95%置信区间（CI）2.71 - 148.34]）和9.44（[95% CI 2.39 - 37.27]）。在持续ADT人群中，基线转移性疾病和睾酮水平也与进展为CRPC相关（HR分别为5.20，95% CI 1.68 - 16.06和HR 0.995，95% CI 0.991 - 0.999）。
在局部晚期或转移性前列腺癌男性患者中，启动ADT时PCA3评分≥35可能预示在接下来3年中发生CRPC的风险较低。
