Abstract：
To explore the clinical parameters and molecular biomarkers that can predict differential pathologic response to neoadjuvant chemohormonal therapy (NCHT) in prostate cancer (CaP).
A total of 128 patients with primary high-risk localized CaP who had received NCHT followed by radical prostatectomy (RP) were included. Androgen receptor (AR), AR splice variant-7 (AR-V7) and Ki-67 staining were evaluated in prostate biopsy specimens by immunohistochemistry. The pathologic response to NCHT in whole mount RP specimens was measured based on the reduction degree of tumor volume and cellularity compared to the paired pretreatment needle biopsy, and divided into 5 tier grades (Grades 0-4). Patients with Grades 2 to 4 (the reduction degree more than 30%) were defined as having a favorable response. Logistic regression was performed to explore the predictive factors associated with a favorable pathologic response. The predictive accuracy was evaluated by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).
Ninety-seven patients (75.78%) had a favorable response to NCHT. Logistic regression showed that the preoperative PSA level, low AR expression and high Ki-67 expression in biopsy specimens were associated with a favorable pathologic response (P < 0.05). Furthermore, the AUC of the preoperative PSA level, AR and Ki-67 were 0.625, 0.624 and 0.723, respectively. Subgroup analysis revealed that the rate of favorable pathologic response to NCHT was 88.5% in patients with ARlowKi-67high, which was higher than patients with ARlowKi-67low, ARhighKi-67low, and ARhighKi-67high (88.5% vs. 73.9%, 72.9%, and 70.9%, all P < 0.05).
A lower preoperative PSA level was an independent predictive factor for a favorable pathologic response. Moreover, the expression status of AR and Ki-67 in biopsy specimens were associated with differential pathologic response to NCHT, and AR low/Ki-67 high was also associated with favorable response but warrants further evaluation in this patient subgroup and future trial clinical trial design.
A total of 128 patients with primary high-risk localized CaP who had received NCHT followed by radical prostatectomy (RP) were included. Androgen receptor (AR), AR splice variant-7 (AR-V7) and Ki-67 staining were evaluated in prostate biopsy specimens by immunohistochemistry. The pathologic response to NCHT in whole mount RP specimens was measured based on the reduction degree of tumor volume and cellularity compared to the paired pretreatment needle biopsy, and divided into 5 tier grades (Grades 0-4). Patients with Grades 2 to 4 (the reduction degree more than 30%) were defined as having a favorable response. Logistic regression was performed to explore the predictive factors associated with a favorable pathologic response. The predictive accuracy was evaluated by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).
Ninety-seven patients (75.78%) had a favorable response to NCHT. Logistic regression showed that the preoperative PSA level, low AR expression and high Ki-67 expression in biopsy specimens were associated with a favorable pathologic response (P < 0.05). Furthermore, the AUC of the preoperative PSA level, AR and Ki-67 were 0.625, 0.624 and 0.723, respectively. Subgroup analysis revealed that the rate of favorable pathologic response to NCHT was 88.5% in patients with ARlowKi-67high, which was higher than patients with ARlowKi-67low, ARhighKi-67low, and ARhighKi-67high (88.5% vs. 73.9%, 72.9%, and 70.9%, all P < 0.05).
A lower preoperative PSA level was an independent predictive factor for a favorable pathologic response. Moreover, the expression status of AR and Ki-67 in biopsy specimens were associated with differential pathologic response to NCHT, and AR low/Ki-67 high was also associated with favorable response but warrants further evaluation in this patient subgroup and future trial clinical trial design.
摘要：
目的：探讨可预测前列腺癌（CaP）新辅助化疗（NCHT）不同病理反应的临床参数和分子生物标志物。
方法：共128例原发性高危性局部CaP患者接受NCHT后进行根治性前列腺切除术（RP）。雄激素受体(AR),通过免疫组织化学评估前列腺活检标本中的AR剪接变体7（AR-V7）和Ki-67染色。与配对预处理针活检相比，根据肿瘤体积和细胞数量的减少程度，测量整个安装RP标本对NCHT的病理反应。分为5个等级（0-4级）。具有2至4级(降低程度超过30%)的患者被定义为具有良好的反应。进行Logistic回归以探索与有利的病理反应相关的预测因素。通过受试者工作特征（ROC）曲线和ROC曲线下面积（AUC）评估预测准确性。
结果：97例患者（75.78%）对NCHT反应良好。Logistic回归显示,术前PSA水平,活检标本中AR低表达和Ki-67高表达与良好的病理反应相关(P<0.05)。此外，术前PSA水平的AUC，AR和Ki-67分别为0.625、0.624和0.723。亚组分析显示，ARlowKi-67high患者对NCHT的有利病理反应率为88.5%，高于ARlowKi-67low患者，ARhighKi-67low,和ARhighKi-67高（88.5%vs.73.9%,72.9%,70.9%，所有P<0.05)。
结论：术前PSA水平降低是良好病理反应的独立预测因素。此外，活检标本中AR和Ki-67的表达状态与NCHT的不同病理反应相关,AR低/Ki-67高也与良好的反应相关,但需要在该患者亚组和未来的试验临床试验设计中进一步评估.
方法：共128例原发性高危性局部CaP患者接受NCHT后进行根治性前列腺切除术（RP）。雄激素受体(AR),通过免疫组织化学评估前列腺活检标本中的AR剪接变体7（AR-V7）和Ki-67染色。与配对预处理针活检相比，根据肿瘤体积和细胞数量的减少程度，测量整个安装RP标本对NCHT的病理反应。分为5个等级（0-4级）。具有2至4级(降低程度超过30%)的患者被定义为具有良好的反应。进行Logistic回归以探索与有利的病理反应相关的预测因素。通过受试者工作特征（ROC）曲线和ROC曲线下面积（AUC）评估预测准确性。
结果：97例患者（75.78%）对NCHT反应良好。Logistic回归显示,术前PSA水平,活检标本中AR低表达和Ki-67高表达与良好的病理反应相关(P<0.05)。此外，术前PSA水平的AUC，AR和Ki-67分别为0.625、0.624和0.723。亚组分析显示，ARlowKi-67high患者对NCHT的有利病理反应率为88.5%，高于ARlowKi-67low患者，ARhighKi-67low,和ARhighKi-67高（88.5%vs.73.9%,72.9%,70.9%，所有P<0.05)。
结论：术前PSA水平降低是良好病理反应的独立预测因素。此外，活检标本中AR和Ki-67的表达状态与NCHT的不同病理反应相关,AR低/Ki-67高也与良好的反应相关,但需要在该患者亚组和未来的试验临床试验设计中进一步评估.
