Overall CV Risk Comparable After Orchiectomy, GnRHa Therapy

The rate of cardiovascular events in prostate cancer patients is similar with surgical and pharmaceutical castration but some men experience a transient increased risk of ischaemic events with orchiectomy

medwireNews: The risk of cardiovascular (CV) events after castration for prostate cancer is comparable with bilateral orchiectomy and gonadotropin-releasing hormone agonist (GnRHa) treatment, Taiwanese researchers have found.

However, their nationwide cohort study identified a transient increase in the rate of CV ischaemic events – defined as any myocardial infarction (MI) or ischaemic stroke (IS) – after treatment with surgical castration versus GnRHa, a risk that was particularly notable for older men and those with a history of CV disease.

“These findings can help clinicians decide on the optimal castration strategy for individual patients”, the team writes in the Journal of Clinical Oncology.

Wen-Kuan Huang, from Chang Gung Memorial Hospital in Linkou, and co-authors collated data for 14,715 Taiwanese men diagnosed with prostate cancer between 1997 and 2011 and treated with bilateral orchiectomy (n=3578) or GnRHa therapy (n=11,137).

After propensity score weighting, the CV ischaemic event rate did not significantly differ between the surgical and GnRHa groups over a median follow-up of 3.3 years, at 1.89 versus 1.63 events per 100 person–years and a hazard ratio (HR) of 1.16.

And the orchiectomy and GnRHa patient groups had similar outcomes when rates of MI and IS were considered individually, as well as for rates of heart failure, all-cause death, CV death, sudden cardiac death and prostate cancer death.

“These findings indicated that the GnRHa use did not increase CV risk in comparison with orchiectomy, providing reassurance when considering GnRHa for the method of [androgen deprivation therapy] in patients with [prostate cancer]”, the researchers say.

But COX proportional regression analysis detected an increased risk of CV ischaemic events with orchiectomy that was limited to the first 1.5 years of follow-up, with a significant HR of 1.40.

This transient risk was associated with age of 65 years or older (HR=1.43), hypertension (HR=1.55), a Charlson comorbidity index score of at least 3 (HR=1.59), and a history of MI, IS or coronary heart disease (HR=1.65).

The researchers hypothesize that the short-term increased risk may be caused by systemic metabolic changes associated with persistent low levels of testosterone, such as insulin resistance, increased body weight and dyslipidaemia, which are, in turn, linked to CV disease.

“The unique phenomenon of testosterone surge after administration of GnRHa, particularly apparent during the first few injected doses, might hinder the suppression of testosterone level as much as did orchiectomy”, they postulate.

Nevertheless, Wen-Kuan Huang et al note that after 1.5 years the CV risk in patients given GnRHa increased to the level associated with orchiectomy, suggesting that “GnRHa use might have a cumulative effect on CV diseases.”

“Further research is needed to elucidate the mechanisms”, they conclude.




Chen D-Y, See L-C, Liu J-R, et al. Risk of cardiovascular ischemic events after surgical castration and gonadotropin-releasing hormone agonist therapy for prostate cancer: A nationwide cohort study. J Clin Oncol; Advance online publication 2 October 2017. https://doi.org/10.1200/JCO.2016.71.4204

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