BACKGROUND: 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. OBJECTIVE: 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). INTERVENTION: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: In this report, we randomized patients undergoingradical 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.
RCT Entities:
BACKGROUND: 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. OBJECTIVE: 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). INTERVENTION: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.
Authors: Stavros Kakkos; George Kirkilesis; Joseph A Caprini; George Geroulakos; Andrew Nicolaides; Gerard Stansby; Daniel J Reddy Journal: Cochrane Database Syst Rev Date: 2022-01-28
Authors: Dominique Farge; Corinne Frere; Jean M Connors; Alok A Khorana; Ajay Kakkar; Cihan Ay; Andres Muñoz; Benjamin Brenner; Pedro H Prata; Dialina Brilhante; Darko Antic; Patricia Casais; María Cecilia Guillermo Esposito; Takayuki Ikezoe; Syed A Abutalib; Luis A Meillon-García; Henri Bounameaux; Ingrid Pabinger; James Douketis Journal: Lancet Oncol Date: 2022-07 Impact factor: 54.433