Use of nonselective beta-blockers (nsBBs) at the time of radical prostatectomy may reduce the risk of prostate cancer recurrence, according to a Norwegian cohort study.

Investigators found that use of nsBBs at the time of prostate cancer surgery was significantly associated with a 36% lower risk of receiving treatment for cancer recurrence, reported Shivanthe Sivanesan, MD, of Oslo University Hospital, and colleagues. They found no such association, however, with the use of selective beta-blockers (sBBs).

Considering the number of radical prostatectomies being performed, “even a small delay in the need for further hormonal therapy and radiotherapy after surgery would justify an interventional study to identify a potential causality between nsBB use and prostate cancer recurrence,” the researchers wrote in JAMA Network Open.

They noted that the perioperative period “is receiving increased attention as a platform to inhibit cancer progression,” and that there is increasing evidence supporting a role for nsBBs in cancer treatment. The team hypothesized, therefore, that use of nsBBs at the time of surgery would be associated with a need for less treatment for cancer recurrence post-prostatectomy.

The cohort study, which the researchers said they believe to be the first to look specifically at an association between use of nsBBs at the time of surgery and recurrence-related treatment, used prospectively collected data from four registries: Cancer Registry of Norway, the Norwegian Patient Registry, the Norwegian Prescription Database, and the Norwegian Cause of Death Registry.

The analysis included data on a total of 11,117 men with prostate cancer who underwent radical prostatectomy, from January 2008 to December 2015, and had a minimum progression-free follow-up of 6 months.

Of these, 1,622 patients (14.6%) received treatment for cancer recurrence during a median follow-up of 4.3 years. A total of 209 patients (1.9%) in the entire cohort were nsBB users, while 1,511 (13.6%) were sBB users at the time of radical prostatectomy. A larger proportion of nsBB users were less healthy (ECOG performance status >1), older, and co-medicated with aspirin, metformin, or a statin at the time of prostatectomy.

Cox proportional hazards regression analysis, using imputed data for missing covariates, showed that nsBB use at the time of surgery was significantly associated with less treatment for recurrence (adjusted hazard ratio [aHR] 0.64, 95% CI 0.42-0.96, P=0.03). A corresponding complete case analysis (n=7,147) had comparable results (aHR 0.51, 95% CI 0.28-0.93, P=0.03).

Use of sBBs was not associated with less treatment for cancer recurrence in either the imputed data set (aHR 0.96, 95% CI 0.84-1.11), or the complete case analysis (aHR 0.94, 95% CI 0.78-1.14).

Study limitations, Sivanesan and co-authors noted, included the lack of postoperative prostate-specific antigen values and an inability to identify biochemical recurrence.

“Treatment for recurrence was therefore used as a surrogate end point, but eligibility for this treatment is influenced by comorbidities and life expectancy, both of which (illustrated by ECOG performance status and deaths not related to prostate cancer) differed significantly between users of nsBBs and nonusers,” the researchers wrote.

And subanalyses with relaxed inclusion criteria allowing for inclusion of patients with early progression (within 6 months) and only the healthiest patients (ECOG performance status of 0) were consistent with the study’s major findings, the team said.

They added that there was a potential for residual confounding from background variables, such as socioeconomic status, race and ethnicity, and smoking habits — information not available in the Norwegian registries.

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