Endoscopic, ultrasound-guided, radiofrequency ablation of aldosterone-producing adenomas (FABULAS): a UK, multicentre, prospective, proof-of-concept trial

Abstract

Background

Unilateral aldosterone-producing adrenal adenomas (APAs) are the potentially curable cause of 5% of all cases of hypertension. Their localisation (via adrenal vein sampling [AVS]) and removal (by laparoscopic adrenalectomy) require invasive procedures that are unattractive to patients. Molecular imaging-located, endoscopic ultrasound-guided trans-gastric radiofrequency ablation (EUS-RFA) is a potential novel, minimally invasive alternative to AVS and total adrenalectomy for the treatment of APAs in the left adrenal gland, which is very close to the stomach. We aimed to determine whether EUS-RFA can safely target a heterogeneous set of such tumours without damaging the rest of the adrenal gland or adjacent organs.

Methods

We conducted a three-centre feasibility study in the UK of EUS-RFA as a non-surgical, adrenal-sparing treatment for left-sided APAs. Eligible participants were men and women aged 18 years or older, with a diagnosis of primary aldosteronism under the Endocrine Society's criteria, and with evidence of a left-sided APA, diagnosed by AVS or PET-CT. Recruitment was done in three groups, with data from the first four patients in the previously recruited group being reviewed by an independent Safety Committee before proceeding. We performed molecular imaging on two occasions, first to diagnose and locate the APA, and later to quantify the degree of ablation. Following a fine-needle biopsy for later confirmation of APA diagnosis, ablation was performed using a 19G ablation catheter. Its manipulation under continuous ultrasound guidance permitted an incremental number of 10–20 s treatments (also known as burns) as the study progressed. The primary endpoint was safety, judged by the occurrence of prespecified major hazards (gastric and adrenal puncture: perforation, haemorrhage, or infarction of major organs) 24 h or 48 h post-ablation. Secondary endpoints were reductions in the proportion of radiotracer uptake by the ablated APA compared with the contralateral adrenal on molecular imaging at 3 months, and international consensus criteria for biochemical and clinical success (reductions in plasma aldosterone to renin ratio and blood pressure 6 months post-RFA).

Findings

Between Feb 21, 2018, and Feb 10, 2023, 44 patients were screened and 28 participants were recruited (21 [75%] male and seven [25%] female, mean age 57·7 years [SD 10·3]; 16 [57%] White, 11 [39%] Black, and one [4%] Asian). The 28 participants underwent 35 ablations on one (21 [75%]) or two (seven [25%]) occasions. All PET-CT-positive nodules were identified by the endoscopic ultrasound probe and successfully penetrated by biopsy and ablation catheters. None of the prespecified major hazards occurred in any patient. Localised reduction of radiotracer uptake by the PET-CT-positive APAs at 3 months was associated with complete or partial biochemical cure in 21 participants (75% [95% CI 55–91]), and with complete or partial cure of hypertension (clinical cure) in 12 participants (43% [24–61]). In four participants, disappearance of the APA on molecular imaging was associated with a systolic blood pressure under 135 mm Hg and diastolic blood pressure under 85 mm Hg off all antihypertensive treatment.

Interpretation

EUS-RFA appears a safe alternative to total adrenalectomy for the treatment of left-sided APAs and has the potential to completely cure primary aldosteronism and hypertension when most of the APA is ablated. These findings have informed the design of a pivotal study of thermal ablation versus surgery, which will determine the full benefits of EUS-RFA.

Funding

National Institute for Health and Care Research Biomedical Research Centres at Barts, University College Hospitals, and Cambridge University Hospitals, Barts Charity, and British Heart Foundation.