Abstract：
Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients. However, data regarding complications of intense hormone therapy and surgical complications are scarce. Our objective was to evaluate the occurrence of cardiovascular (CV) and thromboembolic (TE) adverse events (AE) in patients with localized PC who have received intense neoadjuvant ADT followed by prostatectomy. A comprehensive search in MEDLINE, Embase, Scopus and conference abstracts was performed. The strategies were developed and applied for each electronic database on March 7th, 2023. Eligible studies included randomized and single-arm trials testing ARSIs prior to prostatectomy that adequately reported safety data regarding CV and TE AE, peri-operative complications, and mortality during therapy. Pooled incidence (PI) of AE with 95% confidence interval (95% CI) was estimated using a random effects model. Quality assessment and reporting followed Cochrane Collaboration Handbook and PRISMA guidelines. PROSPERO: CRD42022344104. Nine randomized controlled trials and three single-arm phase II trials were included, comprising 702 patients (702 patients for CV AE and 522 for perioperative complications). The neoadjuvant regimen was classified as monotherapy with ARSI (100 patients), combination therapy with ADT + ARSI (383 patients), or ADT + ARSI + ARSI (219 patients). The PI of TE within the perioperative interval was 4.2% (95% CI = 2.6%-6.6%, I2 = 0.0%, P = .65), and the PI for CV AE was 4.6% (95% CI = 3.1%-6.7%, I2 = 0.0%, P = .71). Seven deaths were reported, resulting in a PI of 2.2% (95% CI = 1.3%-3.8%, I2 = 0.0%, P = .99), of which two were considered treatment-related and occurred within the perioperative period. The PI of hypertension grade 3-5 was 7.3% (95% CI = 4.8%-11.0%, I2 = 38.8%, P = .04). CV and TE AE associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 4.6% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting.
摘要：
一些II期试验已经研究了新辅助新型雄激素受体信号抑制剂（ARSI）与雄激素剥夺疗法（ADT）联合，然后在前列腺癌（PC）患者中进行根治性前列腺切除术（RP）。然而,有关激素强化治疗并发症和手术并发症的数据很少.我们的目的是评估接受强烈新辅助ADT后进行前列腺切除术的局部PC患者的心血管（CV）和血栓栓塞（TE）不良事件（AE）的发生。在MEDLINE中全面搜索,Embase,执行了Scopus和会议摘要。这些策略于3月7日制定并应用于每个电子数据库，2023年。符合条件的研究包括在前列腺切除术前测试ARSI的随机和单臂试验，这些试验充分报告了关于CV和TEAE的安全性数据。围手术期并发症,治疗期间的死亡率。使用随机效应模型估计具有95%置信区间(95%CI)的合并AE发生率(PI)。质量评估和报告遵循Cochrane协作手册和PRISMA指南。PROSPERO：CRD42022344104。包括9项随机对照试验和3项单臂II期试验，包括702例患者(702例CVAE患者和522例围手术期并发症)。新辅助方案被归类为ARSI单药治疗（100例），ADT+ARSI联合治疗（383例患者），或ADT+ARSI+ARSI（219例）。围手术期TE的PI为4.2%(95%CI=2.6%-6.6%,I2=0.0%，P=.65），CVAE的PI为4.6%(95%CI=3.1%-6.7%，I2=0.0%，P=.71）。据报有7人死亡,得到2.2%的PI(95%CI=1.3%-3.8%，I2=0.0%，P=.99)，其中两个被认为与治疗相关，发生在围手术期。3-5级高血压的PI为7.3％（95％CI=4.8％-11.0％，I2=38.8%，P=.04）。在局部PC患者中，与强烈的新辅助激素治疗相关的CV和TEAE可在多达4.6％的病例中发生。我们的数据警告在这种情况下进一步评估血栓风险和预防性抗凝。
