Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer: The ENACT Randomized Clinical Trial.

Importance: There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS). Objective: To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer. Design, Setting, and Participants: The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites. Eligible patients were 18 years or older, had received a diagnosis of histologically proven low-risk or intermediate-risk localized prostate cancer within 6 months of screening, and were undergoing AS. Patients were monitored during 1 year of treatment and up to 2 years of follow-up. Data analysis was conducted in February 2021. Interventions: Randomized 1:1 to enzalutamide, 160 mg, monotherapy for 1 year or continued AS, as stratified by cancer risk and follow-up biopsy type. Main Outcomes and Measures: The primary end point was time to pathological or therapeutic prostate cancer progression (pathological, ≥1 increase in primary or secondary Gleason pattern or ≥15% increased cancer-positive cores; therapeutic, earliest occurrence of primary therapy for prostate cancer). Secondary end points included incidence of a negative biopsy result, percentage of cancer-positive cores, and incidence of a secondary rise in serum prostate-specific antigen (PSA) levels at 1 and 2 years, as well as time to PSA progression. Adverse events were monitored to assess safety. Results: A total of 114 patients were randomized to treatment with enzalutamide plus AS and 113 to AS alone; baseline characteristics were similar between treatment arms (mean [SD] age, 66.1 [7.8] years; 1 Asian individual [0.4%], 21 Black or African American individuals [9.3%], 1 Hispanic individual [0.4%], and 204 White individuals [89.9%]). Enzalutamide significantly reduced the risk of prostate cancer progression by 46% vs AS (hazard ratio, 0.54; 95% CI, 0.33-0.89; P = .02). Compared with AS, odds of a negative biopsy result were 3.5 times higher; there was a significant reduction in the percentage of cancer-positive cores and the odds of a secondary rise in serum PSA levels at 1 year with treatment with enzalutamide; no significant difference was observed at 2 years. Treatment with enzalutamide also significantly delayed PSA progression by 6 months vs AS (hazard ratio, 0.71; 95% CI, 0.53-0.97; P = .03). The most commonly reported adverse events during enzalutamide treatment were fatigue (62 [55.4%]) and gynecomastia (41 [36.6%]). Three patients in the enzalutamide arm died; none were receiving the study drug at the time of death. No deaths were considered treatment-related. Conclusions and Relevance: The results of this randomized clinical trial suggest that enzalutamide monotherapy was well-tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer. Enzalutamide may provide an alternative treatment option for patients undergoing AS. Trial Registration: ClinicalTrials.gov Identifier: NCT02799745.

Results of endovascular therapy and aortobifemoral grafting for Transatlantic Inter-Society type C and D aortoiliac occlusive disease.

OBJECTIVE: The purpose of this study was to compare the outcomes of aortoiliac stenting (AIS) to those of aortobifemoral grafting (ABF) for patients with TransAtlantic Inter-Society Consensus (TASCII) C and D aortoiliac occlusive disease. METHODS: From 1998 to 2007, 32 patients underwent ABF and 40 patients underwent AIS. Kaplan-Meier estimates for patency were used. RESULTS: Patients undergoing AIS were older (66.6 years ABF vs 59.2 years AIS; P=.006). The ABF group had simultaneous profundoplasty (n = 8) and femoral-popliteal graft (n =1). Six patients had treatment for concomitant infrainguinal disease at the time of AIS. There was no mortality in either group. Average hospital stay in the ABF group was 7 +/- 2 days and 1 +/- 0.3 days for AIS (P = .0001). Pulmonary complications predominated in the ABF group (13%). Four patients in the AIS group (10%) developed intraprocedural complications. Primary patency at 48 months was 69 +/- .12% for AIS and 93 +/- .07% for ABF (P = .013). There was a significant increase in ankle-brachial indices after revascularization in both groups. CONCLUSIONS: TASC type C and D lesions can be treated with either ABF or AIS with satisfactory results. Compared with ABF, AIS is associated with decreased primary patency, decreased perioperative morbidity, and shorter hospital stay.