The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study

Abstract

Previous studies have demonstrated an anti-tumoral effect of beta-adrenergic blocking agents on cutaneous melanoma (CM). The aim of this study was to investigate if beta-adrenergic blocking agents have an impact on survival in Swedish patients with melanoma. A population-based retrospective registry study including all patients diagnosed with a primary invasive melanoma between 2009 and 2013 was performed. Data from the Swedish Melanoma Register were linked to the Swedish Prescribed Drug Registry and the Swedish Cause of Death Register. Cox regression analyses including competing risk assessments were performed. There were 12,738 patients included, out of which 3702 were exposed to beta-blockers vs. 9036 non-exposed patients. Age, male sex, Breslow thickness, ulceration, and nodal status were independent negative prognostic factors for melanoma-specific survival (MSS). Adding beta-blockers to the analysis did not add any prognostic value to the model (HR 1.00, p = 0.98), neither when adjusting for competing risks (HR 0.97, p = 0.61). When specifically analyzing the use of non-selective beta-blockers, the results were still without statistical significance (HR 0.76, p = 0.21). In conclusion, this population-based registry study could not verify that the use of beta-adrenergic blocking agents improve survival in patients with melanoma.

β‐Adrenergic signaling in skin cancer

“…Lemeshow et al Katsarelias et al 38 The effect of βadrenergic blocking agents in cutaneous melanoma-a nation-wide Swedish population-based retrospective register study…”

“…Thus, they concluded that βblocker use was not associated with reduced risk of death from melanoma. 37 Katsarelias et al 38 investigated the effects of βblockers in cutaneous melanoma. Of 12,738 patients, 3702 received βblockers, and 9036 did not.…”

“…Thus, the results of this study did not support the hypothesis that the use of βadrenergic blocking agents improves survival in patients with melanoma. 38 Whereas the data on the anticancer effects of βblockers alone remain mixed, some evidence suggests that βblockers may improve outcome when used as an adjunct to immunotherapy. A retrospective study by Kokulus et al 39 showed that βblocker use had an association with better OS in patients treated with immune-based therapies between 2000 and 2015.…”

Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study” Cancers 2020, 12, 3228

“…We read the paper by Katsarelias et al with great interest, regarding the effect of beta-adrenergic blocking agents on cutaneous melanoma [ 1 ]. However, the study presents some methodology biases that do not allow us to support the authors’ conclusions.…”

Reply to Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study.” Cancers 2020, 12, 3228

“…As a general comment, the idea of a positive effect of beta-blockers in reducing recurrence of melanoma is very intriguing [ 1 , 2 ], and therefore our aim was to investigate this in a large cohort of patients. The study was a retrospective registry-based study including 12,738 patients with melanoma, where 3702 were exposed to beta-blockers [ 3 ].…”