我们将肿瘤前列腺特异性膜抗原 (PSMA) 水平描述为癌症生物学和初治前列腺癌治疗敏感性的反映。我们首先将原发性前列腺癌中的 PSMA 正电子发射断层扫描 (PET) 最大标准化摄取值 (SUVmax) 与肿瘤 FOLH1（PSMA RNA 丰度）建立 RNA 作为代理 (n = 55)。然后，我们在两个大型原发性肿瘤队列中发现并验证了与 PSMA RNA 水平相关的分子途径。我们在独立队列（总共 18 个；5684 个肿瘤样本）中验证了这些关联，以描述与 PSMA 相关的途径和治疗反应。PSMA RNA 丰度与 SUVmax 适度相关（ρ = 0.41）。在独立队列中，雄激素受体信号传导在 PSMA 高的肿瘤中更加活跃。因此，当采用雄激素剥夺疗法治疗生化复发时，高 PSMA 肿瘤患者的癌症特异性生存期更长（调整后的风险比 [AHR] 0.54 [0.34-0.87]；n = 174）。 PSMA 低肿瘤具有抗放疗的分子标记。与此一致的是，高 PSMA 肿瘤患者在初次放疗后复发的时间较长（AHR 0.50 [0.28-0.90]；n = 248）。在 SAKK09/10 试验（n = 224）中，接受挽救性放射治疗的高 PSMA 肿瘤患者在 64 Gy 组中经历了更长的进展时间（限制平均生存时间 [RMST] 7.60 [0.05-15.16]），但这种影响在 70 Gy 组中有所减轻（RMST 3.52 [-3.30 至 10.33]）。局限性包括使用 PSMA RNA 作为 PET SUVmax 的替代品。未接受治疗的前列腺癌中的 PSMA 水平可区分肿瘤生物学和治疗敏感性。这些结果需要使用 PET 指标进行验证，以证实基于成像的管理决策。版权所有 © 2024 欧洲泌尿外科协会。由 Elsevier B.V. 出版。保留所有权利。

We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer.We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts. We validated those associations in independent cohorts (18 total; 5684 tumor samples) to characterize the pathways and treatment responses associated with PSMA.PSMA RNA abundance correlates moderately with SUVmax (ρ = 0.41). In independent cohorts, androgen receptor signaling is more active in tumors with high PSMA. Accordingly, patients with high PSMA tumors experienced longer cancer-specific survival when managed with androgen deprivation therapy for biochemical recurrence (adjusted hazard ratio [AHR] 0.54 [0.34-0.87]; n = 174). PSMA low tumors possess molecular markers of resistance to radiotherapy. Consistent with this, patients with high PSMA tumors experience longer time to recurrence following primary radiotherapy (AHR 0.50 [0.28-0.90]; n = 248). In the SAKK09/10 trial (n = 224), patients with high PSMA tumors who were managed with salvage radiotherapy experienced longer time to progression in the 64-Gy arm (restricted mean survival time [RMST] +7.60 [0.05-15.16]), but this effect was mitigated in the 70-Gy arm (RMST 3.52 [-3.30 to 10.33]). Limitations include using PSMA RNA as a surrogate for PET SUVmax.PSMA levels in treatment-naïve prostate cancer differentiate tumor biology and treatment susceptibilities. These results warrant validation using PET metrics to substantiate management decisions based on imaging.Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.