Martínez-Piñeiro Luis, Schalken Jack A, Cabri Patrick, Maisonobe Pascal, de la Taille Alexandre
Urology Unit, Infanta Sofía University Hospital, Madrid, Spain.
BJU Int. 2014 Oct;114(4):608-16. doi: 10.1111/bju.12542. Epub 2014 Apr 4.
To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics.
The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3 change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse events and changes in laboratory parameters.
The intent-to-treat population comprised 322 patients; 39 (12.1%) had non-assessable PCA3 scores at baseline, and 109/322 (33.9%), 215/313 (68.7%) and 232/298 (77.9%) had non-assessable PCA3 scores at 1, 3 and 6 months, respectively. Baseline Gleason score was the only variable associated with non-assessability of PCA3 score at 6 months (P = 0.017) - the hazard of having a non-assessable PCA3 score at 6 months was 1.824-fold higher (95% confidence interval 1.186-2.805) in patients with a Gleason score ≥8 vs those with a Gleason score ≤6. The median PCA3 scores at baseline were significantly higher in patients aged ≥65 years vs those aged <65 years and in patients with a serum PSA level <100 ng/mL vs those with serum PSA level of >200 ng/mL. The median PCA3 score was significantly lower in patients with metastasis than in patients with no metastasis or unknown metastasis status. TMPRSS2-ERG scores ≥35 were considered positive (n = 149 [51.6%]). Age, presence of metastasis, PSA level and Gleason score at baseline were not associated with a significant difference in the proportion of TMPRSS2-ERG-positive scores. The median serum PSA levels decreased from 45.5 ng/mL at baseline to 1.2 ng/mL after 6 months, and as expected, >90% of patients achieved castrate levels of testosterone (<50 ng/dL) at 1, 3, and 6 months during triptorelin treatment. The safety profile reported from this study is consistent with the known safety profile of triptorelin.
These data from the Triptocare study suggest that urinary PCA3 or TMPRSS2-ERG score are not reliable markers of cancer stage in advanced prostate cancer. Urinary PCA3 and TMPRSS2-ERG scores do not appear to be useful in assessing response to ADT in advanced prostate cancer, with most patients having non-assessable scores after 6 months of treatment.
评估晚期和转移性前列腺癌患者在基线时以及接受22.5mg曲普瑞林治疗6个月后的前列腺癌抗原-3（PCA3）和TMPRSS2-ERG评分，并在由不同疾病特征定义的患者组中分析这些评分。
曲普瑞林关怀研究是一项前瞻性、开放标签、多中心、单臂、III期研究，研究对象为局部晚期或转移性前列腺癌且未接受过雄激素剥夺治疗（ADT）的男性患者，给予其22.5mg曲普瑞林治疗。主要目的是根据基线变量模拟6个月时尿PCA3的变化。其他结局指标包括尿PCA3和TMPRSS2-ERG评分及状态，以及ADT开始时、开始后1、3和6个月时的血清睾酮和前列腺特异性抗原（PSA）水平。通过记录不良事件和实验室参数变化来评估安全性。
意向性治疗人群包括322例患者；39例（12.1%）在基线时PCA3评分不可评估，109/322例（33.9%）、215/313例（68.7%）和232/298例（77.9%）分别在1、3和6个月时PCA3评分不可评估。基线Gleason评分是与6个月时PCA3评分不可评估性相关的唯一变量（P = 0.017）——Gleason评分≥8的患者在6个月时PCA3评分不可评估的风险比Gleason评分≤6的患者高1.824倍（95%置信区间1.186 - 2.805）。≥65岁患者的基线PCA3评分中位数显著高于<65岁患者，血清PSA水平<100 ng/mL的患者的基线PCA3评分中位数显著高于血清PSA水平>200 ng/mL的患者。有转移的患者的PCA3评分中位数显著低于无转移或转移状态未知的患者。TMPRSS2-ERG评分≥35被视为阳性（n = 149 [51.6%]）。年龄、转移情况、PSA水平和基线Gleason评分与TMPRSS2-ERG阳性评分比例的显著差异无关。血清PSA中位数从基线时的45.5 ng/mL降至6个月后的1.2 ng/mL，正如预期的那样，在曲普瑞林治疗期间，>90%的患者在1、3和6个月时达到了去势水平的睾酮（<50 ng/dL）。本研究报告的安全性概况与曲普瑞林已知的安全性概况一致。
曲普瑞林关怀研究的这些数据表明，尿PCA3或TMPRSS2-ERG评分在晚期前列腺癌中并非可靠的癌症分期标志物。尿PCA3和TMPRSS2-ERG评分在评估晚期前列腺癌对ADT的反应方面似乎并无用处，大多数患者在治疗6个月后评分不可评估。
