The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Eur Urol. 2020 Sep;78(3):360-368. doi: 10.1016/j.eururo.2020.05.001. Epub 2020 May 19.
Direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis (PP) after radical prostatectomy (RP) to prevent venous thromboembolism (VTE) leading to significant practice variation.
To study the impact of in-hospital PP on symptomatic VTE incidence and adverse events after RP at 30 d, with the secondary objective of evaluating overall VTE in a screening subcohort.
DESIGN, SETTING, AND PARTICIPANTS: A prospective, phase 4, single-center, randomized trial of men with prostate cancer undergoing open or robotic-assisted laparoscopic RP was conducted (July 2017-November 2018).
PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d.
The primary efficacy outcome was symptomatic VTE incidence (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall VTE, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. Fisher's exact test and modified Poisson regression were performed.
A total of 501 patients (75% robotic) were randomized and >99% (500/501) completed follow-up. At second interim analysis (N = 445), the symptomatic VTE rate was 2.3% (four PE + DVT and one DVT) for routine care versus 0.9% (one PE + DVT and one DVT) for PP (relative risk 0.40 [95% confidence interval 0.08-2.03], p = 0.3) meeting a futility threshold for early stopping. In the screening subcohort, the overall VTE rate was 3.3% versus 2.4% (p = 0.7). Results were similar at the final analysis (symptomatic VTE: 2.0% vs 0.8%, p = 0.3; overall VTE: 2.9% vs 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All VTE events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection.
This study was not able to demonstrate a statistically significant reduction in symptomatic VTE associated with PP. There was no increase in the development of symptomatic lymphoceles, bleeding, or other adverse events. Given that the event rate was lower than powered for, further research is needed among high-risk patients (Caprini score ≥8) or patients receiving pelvic lymph node dissection.
In this report, we randomized patients undergoing radical prostatectomy to perioperative pharmacologic prophylaxis or routine care alone. We found that pharmacologic prophylaxis did not reduce postoperative symptomatic venous thromboembolism significantly for men at routine risk. Importantly, pharmacologic prophylaxis did not increase adverse events, such as formation of lymphoceles or bleeding, and can safely be implemented when indicated for patients with risk factors undergoing radical prostatectomy.
目前缺乏直接高质量证据评估根治性前列腺切除术（RP）后预防静脉血栓栓塞（VTE）的围手术期药物预防（PP），这导致了显著的实践差异。
研究住院期间 PP 对 RP 后 30 天症状性 VTE 发生率和不良事件的影响，次要目的是在筛查亚组中评估总体 VTE。
设计、设置和参与者：一项前瞻性、4 期、单中心、随机试验纳入了接受开放或机器人辅助腹腔镜 RP 的前列腺癌男性（2017 年 7 月至 2018 年 11 月）。
PP（皮下肝素）加常规护理与常规护理。筛查亚组在 30 天接受下肢多普勒超声检查。
主要疗效结局是症状性 VTE 发生率（肺栓塞[PE]或深静脉血栓形成[DVT]）。主要安全性结局包括手术后出现症状性淋巴囊肿、血肿或出血的发生率。次要结局是总体 VTE、估计失血量、总手术引流量、并发症和监测影像学偏倚。采用 Fisher 确切检验和修正泊松回归进行分析。
共纳入 501 例（75%为机器人）患者进行随机分组，>99%（500/501）完成随访。在第二次中期分析（N=445）中，常规护理组症状性 VTE 发生率为 2.3%（4 例 PE+DVT 和 1 例 DVT），PP 组为 0.9%（1 例 PE+DVT 和 1 例 DVT）（相对风险 0.40[95%置信区间 0.08-2.03]，p=0.3），达到早期停止试验的无效阈值。在筛查亚组中，总体 VTE 发生率为 3.3%对 2.4%（p=0.7）。最终分析结果相似（症状性 VTE：2.0%对 0.8%，p=0.3；总体 VTE：2.9%对 2.8%，p=1）。安全性或次要结局无差异。所有 VTE 事件（7 例症状性和 3 例无症状性）均发生在接受盆腔淋巴结清扫术的患者中。
本研究未能证明 PP 与症状性 VTE 减少具有统计学意义。PP 并未增加症状性淋巴囊肿、出血或其他不良事件的发生。鉴于事件发生率低于预期，高危患者（Caprini 评分≥8）或接受盆腔淋巴结清扫术的患者需要进一步研究。
在本报告中，我们将接受根治性前列腺切除术的患者随机分为围手术期药物预防组或常规护理组。我们发现，药物预防对常规风险的男性术后症状性静脉血栓栓塞无显著降低作用。重要的是，药物预防并未增加淋巴囊肿或出血等不良事件的发生，当有危险因素的患者需要进行根治性前列腺切除术时，药物预防可以安全实施。
