Li Heng, Wang Zhize, Zhang Yucong, Sun Guoliang, Ding Beichen, Yan Libin, Liu Haoran, Guan Wei, Hu Zhiquan, Wang Shaogang, Cheng Fei, Xu Hua, Zhang Xu, Ye Zhangqun
Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
J Cancer. 2019 Jun 2;10(14):3102-3111. doi: 10.7150/jca.30384. eCollection 2019.
: The programmed death 1 (PD1)/programmed death ligand 1 (PDL1) targeted therapies have gained positive outcomes in several tumors, but the evidence of the expression and prognosis value of PD1/PDL1 in high risk prostate cancer was rare. : Immunohistochemical analysis of PDL1/PD1 expression by a validated antibody was performed in a retrospectively collected high risk prostate cancer cohort who received adjuvant hormonal therapy (AHT) after radical prostatectomy (RP). The association between PDL1/PD1 expression and prognosis was determined. : In total, 127 patients were enrolled. 49.6% patients were considered PDL1-high expression while the PD1-positive expression proportion was 24.4%. High PDL1 and negative PD1 expression were significantly associated with lower prostate specific antigen (PSA) density (p=0.010 and p=0.033, respectively). Compared with the PDL1-low expression patients, the PDL1-high expression patients had significantly shorter time to PSA nadir (TTN) (P=0.001) and biochemical recurrence (BCR) (P=0.004). In Kaplan-Meier analysis, the PDL1-high expression group (p<0.0001) and the PDL1-high/PD1-negative expression group (p<0.0001) showed markedly lower BCR-free survival in localized disease. Univariate cause-specific Cox proportional hazard regression model concluded total PSA (p=0.047), PDL1-high-expression (p<0.001), PDL1-high/PD1-negative expression (p<0.001) were significant risk factors of shorter progression time to BCR in localized disease. PDL1-high-expression was the independent predictor of time to BCR in multiple Cox regression of all patients (Hazard ratio [HR]: 3.901; 95% Confidence interval [CI]: 1.287-11.824; p=0.016). : PDL1 expression is not only highly prevalent in high-risk prostate cancer, but is also an independent biomarker in the prognosis of high-risk prostate cancer received AHT after RP. PDL1/PD1 targeted therapy might be a potentially adjuvant treatment option for high-risk prostate cancer after RP.
程序性死亡1(PD1)/程序性死亡配体1(PDL1)靶向治疗在多种肿瘤中取得了积极疗效,但关于PD1/PDL1在高危前列腺癌中的表达及预后价值的证据却很少。对一组回顾性收集的高危前列腺癌队列进行了免疫组化分析,这些患者在根治性前列腺切除术(RP)后接受了辅助激素治疗(AHT),采用经过验证的抗体检测PDL1/PD1的表达。确定了PDL1/PD1表达与预后之间的关联。总共纳入了127例患者。49.6%的患者被认为是PDL1高表达,而PD1阳性表达比例为24.4%。高PDL1和阴性PD1表达分别与较低的前列腺特异性抗原(PSA)密度显著相关(p分别为0.010和0.033)。与PDL1低表达患者相比,PDL1高表达患者达到PSA最低点的时间(TTN)(P=0.001)和生化复发(BCR)时间(P=0.004)显著缩短。在Kaplan-Meier分析中,PDL1高表达组(p<0.0001)和PDL1高表达/PD1阴性表达组(p<0.0001)在局限性疾病中的无BCR生存率明显较低。单因素病因特异性Cox比例风险回归模型得出,总PSA(p=0.047)、PDL1高表达(p<0.001)、PDL1高表达/PD1阴性表达(p<0.001)是局限性疾病中BCR进展时间较短的显著风险因素。在所有患者的多因素Cox回归中,PDL1高表达是BCR时间的独立预测因素(风险比[HR]:3.901;95%置信区间[CI]:1.287-11.824;p=0.016)。PDL1表达不仅在高危前列腺癌中高度普遍,而且是RP后接受AHT的高危前列腺癌预后的独立生物标志物。PDL1/PD1靶向治疗可能是RP后高危前列腺癌的一种潜在辅助治疗选择。