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WASHINGTON -- A retrospective analysis of close to 40,000 men with high-risk prostate cancer treated at Veterans Affairs (VA) health systems found no association between beta blocker use and a reduction in mortality.

While unadjusted analyses at over 11 years of follow-up favored men taking the selective beta-1 blocker metoprolol compared to those not on any beta blocker, multivariable analysis revealed no differences in survival outcomes or skeletal-related events:

• Overall survival (HR 0.97, 95% CI 0.93-1.02)
• Cancer-specific survival (HR 0.94, 95% CI 0.85-1.04)
• Skeletal-related events (HR 1.00, 95% 0.87-1.15)

Findings from the analysis were reported by Natasza Posielski, MD, of the University of Wisconsin School of Medicine and Public Health in Madison, during a poster session here at the Society of Urologic Oncology annual meeting.

"With the number of medications in this arena of advanced castration-resistant prostate cancer it's important to focus on the ones that might potentially have an effect, and this suggests that beta blockers are probably not one of them," Posielski told MedPage Today.

Prior epidemiologic studies looking at breast, ovarian, and other cancers have demonstrated a positive association between beta blocker use and disease progression.

Posielski said the impetus for the current research was a paper in that examined beta adrenergic receptor signaling in a prostate cancer mouse model and discovered that beta receptor signaling was implicated in angiogenesis and a switch from hyperplasia to rapid tumor growth. When the beta receptor was knocked out this angiogenesis and tumor growth ceased, suggesting that beta blockers might have a potential role in improving oncologic outcomes.

Furthermore, a of 3,561 high-risk prostate cancer patients in Norway showed an association between beta blocker use and reduced cancer-specific mortality (HR 0.79, 95% CI 0.68-0.91, P=0.001), though no significant association was found with all-cause mortality (HR 0.92, 95% CI 0.83-1.02).

"We were really excited to test this out in our patient population hoping to see that same outcome and did not, but I think that's pretty significant because our numbers are much higher, follow-up is really good," Posielski said.

Initially, her team examined all beta blockers for an association with survival, but none was seen, so they narrowed their focus on metoprolol as suggested it had the strongest association with decreased prostate cancer incidence.

For their study, Posielski and colleagues examined data on 28,975 men not on beta blockers and 10,223 on metoprolol who were treated at a VA health system and filled their prescriptions at VA pharmacies. Patients all had a prostate-specific antigen (PSA) level greater than 20 ng/mL and were excluded if they received less than 6 months of androgen deprivation therapy (ADT) or if they received ADT plus chemoradiotherapy as their primary treatment.

In an unadjusted analysis, median overall survival was 5.5 years in the metoprolol group and 4.2 years in the no beta-blocker group (P<0.001). Death from prostate cancer occurred in 11.6% and 12.2% of the two groups, respectively. Skeletal-related events occurred in 7.6% of the no beta blocker group (median time to event of 4 years) and 8.5% of the metoprolol group (median time of 5.2 years).

But a host of significant differences were seen between the no beta blocker and metoprolol groups (P<0.001 for all): median age (76 vs 75 years, respectively), median PSA (50.3 vs 44.3 ng/mL), and aspirin (28.8% vs 49.9%) and statin use (46.2% vs 75.1%). A smaller proportion of patients were also treated with local therapy in the no beta blocker group (4.4% vs 5.2%, P=0.001). Other significant imbalances included differences in Charlson-comorbidity scores, Gleason score, and white or black race.

Posielski noted that when aspirin and statin use was factored into a multivariate model in the Norwegian study it negated their overall findings. She added that similar research to her group's current study but with statins demonstrated "very impressive" hazard ratios -- in the range of 0.65 for overall and cancer-specific survival.

"As you would imagine, a lot of patients on beta blockers are also on statins so it's really important to factor that into your multivariate analysis," she said.

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