Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis
Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis
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DOI：
10.3389/fonc.2018.00623
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发表时间：
2018-12-20
影响因子：
4.7
通讯作者：
Offermann, Anne
中科院分区：
文献类型：
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作者：
Hupe, Marie Christine;Philippi, Christian;Offermann, Anne
背景资料：在初次诊断时将前列腺癌（PCa）患者分为风险组，使风险适应性疾病管理成为可能，这仍然是一个重大的临床挑战。评估PSMA（前列腺特异性膜抗原）对PCa的预后潜力的现有研究是在根治性前列腺切除术标本（RPE）上进行的，即，在样本分析时，疾病管理的决策已经完成。我们的研究的目的是评估PSMA表达的预后价值PCa患者的活检标本在初诊时，在294例前列腺活检相应的RPE，621原发肿瘤病灶的242 RPE，43个局部晚期或复发肿瘤，34个淋巴结转移，78个远处转移和52个良性前列腺标本PSMA的表达进行了评估。PSMA表达与临床病理特征相关。主要终点是无复发生存期。其他临床病理特征包括WHO/ISUP分级组、PSA血清水平、TNM分期和R状态。卡方检验，方差分析，Cox回归，对数秩检验进行统计analysis.Results：高PSMA表达活检和RPE显着相关的较高风险的疾病复发后根治性手术。活检显示PSMA无表达、低表达、中表达和高表达的患者的5年无复发生存率分别为88.2%、74.2%、67.7%和26.8%。在多变量分析中，活检组织中PSMA高表达是显著的，预测疾病复发风险增加4倍，独立于已建立的预后标志物。结论：PSMA是一个独立的预后指标，活检在初步诊断时，可以预测疾病复发后的根治性治疗PCa。我们的研究提出了应用常规使用的IHC标志物PSMA进行结果预测和决策，在初次诊断时对活检进行风险适应性PCa管理。
Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis enabling a risk-adapted disease management is still a major clinical challenge. Existing studies evaluating the prognostic potential of PSMA (prostate-specific membrane antigen) for PCa were performed on radical prostatectomy specimens (RPE), i.e., decision making for disease management was already completed at time of sample analysis. Aim of our study was to assess the prognostic value of PSMA expression for PCa patients on biopsies at time of initial diagnosis.Methods: PSMA expression was assessed by immunohistochemistry on 294 prostate biopsies with corresponding RPE, 621 primary tumor foci from 242 RPE, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases and 52 benign prostatic samples. PSMA expression was correlated with clinico-pathologic features. Primary endpoint was recurrence free survival. Other clinicopathologic features included WHO/ISUP grade groups, PSA serum level, TNM-stage, and R-status. Chi-square test, ANOVA-analyses, Cox-regression, and log-rank tests were performed for statistical analyses.Results: High PSMA expression on both biopsy and RPE significantly associates with a higher risk of disease recurrence following curative surgery. The 5-year-recurrence free survival rates were 88.2, 74.2, 67.7 and 26.8% for patients exhibiting no, low, medium, or high PSMA expression on biopsy, respectively. High PSMA expression on biopsy was significant in multivariate analysis predicting a 4-fold increased risk of disease recurrence independently from established prognostic markers. PSMA significantly increases during PCa progression.Conclusion: PSMA is an independent prognostic marker on biopsies at time of initial diagnosis and can predict disease recurrence following curative therapy for PCa. Our study proposes the application of the routinely used IHC marker PSMA for outcome prediction and decision making in risk-adapted PCa management on biopsies at time of initial diagnosis.