ADT after radiotherapy does not worsen MACE risk

Androgen deprivation therapy (ADT) does not seem to aggravate the likelihood of major adverse cardiovascular events (MACEs) in prostate cancer patients after curative radiotherapy (RT), according to a recent Singapore study.

“The strengths of the current study are the large size and complete long-term follow-up in the Southeast Asian men with prostate cancer from two prospectively established registry databases,” the researchers said. “Compared with previous studies of the Chinese or Japanese population, our study included a more diversified multi-ethnic group from Southeast Asia.”

Drawing from databases of Singapore’s National Cancer Centre and National Heart Centre, the present observational study included 1,940 patients enrolled between 2000 and 2019. Most participants (n=1,446) received both RT and ADT, while 494 underwent RT alone. The primary outcome of interest was MACE, defined as stroke, cardiovascular death, myocardial infarction, or unstable angina.

Pre-existing cardiovascular risk factors were very common participants, with over 80 percent having at least one such predisposing parameter. RT+ADT patients saw a higher prevalence of cardiovascular risk factors than RT-only comparators (83.6 percent vs 78.1 percent; p=0.01). [Cardiooncology 2022;8:4]

Despite this difference in risk factors, the RT+ADT group was found to have a comparable 1-year cumulative incidence of MACEs as RT-only participants (1.1 percent vs 1.2 percent, respectively).

MACEs continued to occur at similar rates between the RT+ADT vs RT groups at 3 years (5 percent vs 5.2 percent) and 9 years (16.2 percent vs 17.6 percent). Regression modelling confirmed that ADT did not significantly impact the likelihood of MACE development (subdistribution hazard ratio [SHR], 1.01, 95 percent confidence interval [CI], 0.78–1.30; p=0.969).

A similar effect was reported for myocardial infarction, the most common type of MACE event in both arms (75 percent in RT vs 66.5 percent in RT+ADT).

Multivariable analysis revealed that older age (≥70 vs <70 years: SHR, 1.35, 95 percent CI, 1.05–1.72; p=0.018), Indian ethnicity (vs Chinese: SHR, 1.79, 95 percent CI, 1.11–2.87; p=0.016), a prior history of MACE (SHR, 1.75, 95 percent CI, 1.21–2.53; p=0.003), baseline use of metformin (SHR, 1.56, 95 percent CI, 1.15–2.10; p=0.004), and having ≥1 cardiovascular risk factor at baseline (SHR, 1.73, 95 percent CI, 1.08–2.76; p=0.022) were significant predictors of MACEs.

Nevertheless, additional ADT led to a slightly elevated risk of all-cause mortality (SHR, 1.23, 95 percent CI, 0.99–1.52) and of prostate cancer death (SHR, 1.14, 95 percent CI, 0.72–1.80).

“Cardiovascular disease is the leading cause of noncancer deaths in men with prostate cancer. The incidence of secondary cardiovascular events after ADT varies greatly depending on underlying risk factors,” the researchers said.

However, “in our study, despite pre-existing cardiovascular risk factors being common, new MACE within the first year was low … ADT was not found to increase secondary events in our cohort,” they added.

“Novel predictive cardiac biomarkers are urgently needed to identify men at risk and mitigate ADT-related cardiotoxicities,” the researchers said.