Association of β-Blocker Use at Time of Radical Prostatectomy With Rate of Treatment for Prostate Cancer Recurrence

Abstract

The perioperative period has gained attention as a window of opportunity to prevent cancer recurrence. Evidence in support of a role for nonselective β-blockers (nsBBs) in cancer treatment is increasing, and counteracting cancer recurrence associated with perioperative stress and catecholamine is one of the suggested mechanisms of action. To explore whether use of nsBBs at the time of radical prostatectomy is associated with a lower rate of treatment for prostate cancer recurrence. This cohort study analyzed prospectively collected data from the Cancer Registry of Norway, Norwegian Patient Registry, Norwegian Prescription Database, and Norwegian Cause of Death Registry. Of 12 298 eligible patients, this study included 11 117 treatment-naive patients with prostate cancer (ie, no prior hormonal therapy, radiotherapy, or chemotherapy) who underwent radical prostatectomy in Norway from January 1, 2008, to December 31, 2015, with a minimum progression-free follow-up of 6 months. Data analysis was performed from April 20, 2020, to April 30, 2021. Use of nsBBs and selective β-blockers (sBBs) at time of radical prostatectomy. Treatment for cancer recurrence after radical prostatectomy (defined as initiation of hormonal therapy, radiotherapy, or chemotherapy) or, if no treatment was identified, cancer-specific mortality. The study included 11 117 men with prostate cancer (median [IQR] age at radical prostatectomy, 64.8 [60.4-68.3] years). Of these, 1622 (14.6%) later received treatment for cancer recurrence during a median follow-up of 4.3 years (IQR, 2.4-6.3 years). Use of nsBBs at time of surgery among 209 patients was significantly associated with a lower risk of treatment for cancer recurrence (adjusted hazard ratio [aHR], 0.64; 95% CI, 0.42-0.96; P = .03). No such association was observed for use of sBBs (aHR, 0.96; 95% CI, 0.84-1.11; P = .62). Subanalyses with (1) relaxed inclusion criteria allowing for inclusion also of patients with early progression (within 6 months) and (2) only the healthiest patients (Eastern Cooperative Oncology Group performance status of 0) supported the main findings. In this cohort study, use of nsBB but not sBBs at the time of radical prostatectomy was associated with less treatment initiation for cancer recurrence. This finding, together with accumulated preclinical and clinical evidence, provides a foundation for initiation of an interventional study.