Dr. Patel notes that in 2020 there will be 192,000 cases of prostate cancer diagnosed, with 50% of low- and intermediate-risk men receiving radical prostatectomy. Post-surgical venous thromboembolism is associated with significant morbidity, including death, recurrent venous thromboembolism, venous stasis syndrome, venous ulcer, and chronic thromboembolic pulmonary hypertension. Prevention of venous thromboembolism includes early ambulation, intermittent pneumatic compression devices, and pharmacologic prophylaxis. According to most guidelines (ACCP, NICE, NCCN), radical prostatectomy by any approach classifies a patient as high-risk (Caprini risk score ≥ 5). However, direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis after radical prostatectomy to prevent venous thromboembolism leading to significant practice variation. Furthermore, there is no accepted standard practice for venous thromboembolism prophylaxis after radical prostatectomy, with 98% receiving pharmacologic prophylaxis in the UK (61% post-discharge) compared to 17.8% in the US receiving pharmacologic prophylaxis. The objective of the Phase IV PREVENTER prospective, single-center, randomized trial was to assess the impact of in-hospital pharmacologic prophylaxis on symptomatic venous thromboembolism incidence and adverse events after radical prostatectomy at 30 days, with the secondary objective of evaluating overall venous thromboembolism in a screening sub-cohort.
This study included men with prostate cancer undergoing open or robotic-assisted laparoscopic radical prostatectomy between July 2017 and November 2018. The intervention was pharmacologic prophylaxis (subcutaneous heparin) plus routine care versus routine care alone. The screening sub-cohort was offered lower extremity duplex ultrasound at 30 days postoperatively. The trial utilized block randomization, assigning unblinded patients 1:1. The primary efficacy outcome was symptomatic venous thromboembolism incidence (pulmonary embolism or deep venous thrombosis). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall venous thromboembolism, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. As follows is the trial schema:
The final sample included 501 patients (75% robotic) who were randomized and >99% (500/501) completed follow-up. At second interim analysis (n = 445), the symptomatic venous thromboembolism rate was 2.3% (four pulmonary embolisms + deep vein thrombosis and one deep vein thrombosis) for routine care versus 0.9% (one pulmonary embolism + deep vein thrombosis and one deep vein thrombosis) for pharmacologic prophylaxis (relative risk 0.40, 95% confidence interval [CI] 0.08-2.03, p = 0.3) meeting a futility threshold for early stopping. In the screening sub-cohort, the overall venous thromboembolism rate was 3.3% versus 2.4% (p = 0.70). Results were similar at the final analysis (symptomatic venous thromboembolism: 2.0% vs. 0.8%, p = 0.30; overall venous thromboembolism: 2.9% vs. 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All venous thromboembolism events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection, with the majority occurring in the first two weeks after surgery. Furthermore, there was a slightly higher venous thromboembolism rate among patients undergoing open (2.4%) compared to robotic (1.1%) prostatectomy, but the difference was not statistically significant.
Limitations of the PREVENTER trial included: (i) a single institution assessment, with 75% of the cases being performed robotically, (ii) the trial was underpowered for the event rate observed, (iii) patients were not blinded, (iv) few patients had a Caprini score ≥ 8, and (v) the trial did not mandate screening ultrasonography of all patients.
Dr. Patel concluded with several conclusions and implications from this clinical trial:
- In hospital pharmacologic prophylaxis was not associated with a significant reduction in symptomatic or overall venous thromboembolism after radical prostatectomy when added to routine care
- There was no increase in symptomatic lymphoceles, hematoma, bleeding, or other adverse events with pharmacologic prophylaxis
- Patients with a Caprini score ≥ 8 deserve further evaluation (in hospital and potentially extended pharmacologic prophylaxis)
- The results of the PREVENTER trial may be applicable to other surgeries that may be performed in a minimally-invasive fashion with low morbidity and short hospital length of stay (<48 hours)
Presented by: Hiten D. Patel, MD, MPH, Clinical Instructor of Urology, Loyola University Medical Center, Loyola University, Chicago, Illinois
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC
Reference:
1. Patel, Hiten D., Farzana A. Faisal, Bruce J. Trock, Gregory A. Joice, Zeyad R. Schwen, Phillip M. Pierorazio, Michael H. Johnson et al. "Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial." European Urology (2020).