Perioperative propranolol during robotic-assisted radical prostatectomy: A randomised, double-blind, placebo-controlled, pilot trial (PeP-RALP).
This study aimed to determine the feasibility and safety of administering perioperative propranolol, as an adjunct to reduce prostate cancer recurrence, in patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) for European Association of Urology (EAU) intermediate- or high-risk prostate cancer.
Treatment-naïve men aged 40-80 years with EAU intermediate- or high-risk prostate cancer scheduled for RALP were enrolled in this single-centre, randomised, double-blind, placebo-controlled, phase 2 pilot trial. Participants were randomised 1:1 to receive propranolol or placebo for approximately 3 weeks (about 1 week pre-RALP and 2 weeks post-RALP). Serial blood sampling was performed to measure catecholamine metabolites, serum propranolol and short-interval prostate-specific antigen (PSA) dynamics. Participants self-monitored pulse rate and blood pressure twice daily.
Over 36 weeks in 2023, 160 patients underwent RALP; 111 were prescreened, 49 were fully screened and 40 were randomised, corresponding to inclusion rates of 36% among prescreened and 82% among fully screened patients. Pre-RALP adherence was 98% in both arms; post-RALP adherence was lower in the propranolol arm. No Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≥3 adverse events were attributed to propranolol, and no surgeries were delayed. The epinephrine metabolite metanephrine increased intraoperatively in both arms and declined by the end of treatment. Mean preoperative PSA decreased more with propranolol than with placebo. As this pilot was not powered to detect between-group differences, such differences are hypothesis-generating only.
PeP-RALP demonstrated that perioperative propranolol is operationally feasible and demonstrated an acceptable safety profile within RALP workflows, with strong preoperative adherence. Our study supports a multicentre efficacy randomised controlled trial with standardised anaesthetic protocols, postoperative adherence support and oncological endpoints. All physiological and molecular results, including PSA dynamics, in this pilot are exploratory and solely intended to inform the design of any future trials.
Treatment-naïve men aged 40-80 years with EAU intermediate- or high-risk prostate cancer scheduled for RALP were enrolled in this single-centre, randomised, double-blind, placebo-controlled, phase 2 pilot trial. Participants were randomised 1:1 to receive propranolol or placebo for approximately 3 weeks (about 1 week pre-RALP and 2 weeks post-RALP). Serial blood sampling was performed to measure catecholamine metabolites, serum propranolol and short-interval prostate-specific antigen (PSA) dynamics. Participants self-monitored pulse rate and blood pressure twice daily.
Over 36 weeks in 2023, 160 patients underwent RALP; 111 were prescreened, 49 were fully screened and 40 were randomised, corresponding to inclusion rates of 36% among prescreened and 82% among fully screened patients. Pre-RALP adherence was 98% in both arms; post-RALP adherence was lower in the propranolol arm. No Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade ≥3 adverse events were attributed to propranolol, and no surgeries were delayed. The epinephrine metabolite metanephrine increased intraoperatively in both arms and declined by the end of treatment. Mean preoperative PSA decreased more with propranolol than with placebo. As this pilot was not powered to detect between-group differences, such differences are hypothesis-generating only.
PeP-RALP demonstrated that perioperative propranolol is operationally feasible and demonstrated an acceptable safety profile within RALP workflows, with strong preoperative adherence. Our study supports a multicentre efficacy randomised controlled trial with standardised anaesthetic protocols, postoperative adherence support and oncological endpoints. All physiological and molecular results, including PSA dynamics, in this pilot are exploratory and solely intended to inform the design of any future trials.
Authors
Sivanesan Sivanesan, Ramberg Ramberg, Kristiansen Kristiansen, Thapa Thapa, Bjøre Bjøre, Berge Berge, Ottosson Ottosson, Brennhovd Brennhovd, Storås Storås, Thorsby Thorsby, Dahl Dahl, Urbanucci Urbanucci, Grytli Grytli, Bjerke Bjerke, Taskén Taskén
View on Pubmed