A decade of PAE data demonstrates the procedure’s safety and efficacy: “Its time is now”

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PAE
Francisco Carnevale

Ten-year data published in Radiology show that prostate artery embolization (PAE) is a safe and effective treatment for men with benign prostatic hyperplasia (BPH), which can result in long-term improvements in lower urinary tract symptoms (LUTS) and quality of life. Francisco Carnevale (University of São Paulo Medical  School, São Paulo, Brazil) and colleagues note that, prior to their study, long-term experience with PAE for BPH was “limited”. They state that this research is an “important contribution” towards the wider medical community’s understanding of PAE not as an experimental procedure, but “as another alternative for patients suffering from LUTS related to BPH”.

Carnevale and colleagues set out to evaluate the efficacy, safety, and long-term results of PAE for BPH through a retrospective, single-centre study. Between June 2008 and June 2018, a total of 317 men (mean age, 65±8 years) were treated with the minimally-invasive procedure for the alleviation of moderate to severe BPH-related symptoms. PAE was performed with 100–500μm embolic microspheres, and the investigators report a 94% technical success rate for the procedure.

Patient follow-up ranged from three months to 96 months (mean, 27 months). International Prostate Symptom Score (IPSS), quality-of-life score, maximum urinary flow rate, post-void residual volume, prostate-specific antigen (PSA), and prostate volume were all assessed at baseline and during follow-up. Mean maximum improvement was as follows: IPSS, 16±7 points; quality-of-life score, 4±1 points; prostatic volume reduction, 39±39cm3 (39%±29); maximum urinary flow rate, 6±10mL/sec (155%±293); and post-void residual volume, 70±121mL (48% 81) (p<0.05 for all). Early clinical failure occurred in six (1.9%) and symptom recurrence in 72 (23%) men at a median follow-up of 72 months.

Unilateral PAE was associated with higher LUTS recurrence (42% vs. 21%; p=0.04), but the study authors note that the unilateral PAE cohort were on average slightly older than those treated with bilateral PAE (71 years old vs. 65 years old). However, log-rank analysis comparing unilateral and bilateral PAE groups showed no statistically significant difference in the median time to recurrence (48 months and 72 months, respectively; p=0.19).

Embolic particle size did not relate to symptom recurrence, with no difference observed in the median time to recurrence among men treated with microspheres 100–300μm or 300–500μm in diameter.

Baseline PSA was inversely related with recurrence, and was found to be an independent predictor of recurrence outcomes after PAE (hazard ratio [HR], 0.9 per nanograms per millilitre of PSA; 95% confidence interval [CI], 0.8, 0.9; p<0.001).

None of the patients presented with urinary incontinence or erectile dysfunction, an “important finding”, according to Carnevale.

Speaking to Interventional News, Carnevale stresses the significance of this research, the first decade-long dataset to follow-up outcomes in over 300 PAE patients: “It was published in the most reviewed journal with the highest impact factor in the radiology field. Urological societies have been waiting for these long-term data to decide if [they trust that] PAE can be offered as another alternative treatment for patients suffering from LUTS related to BPH. These data consolidate the pioneering, multidisciplinary work done by the Radiology and Urology Departments at the University of São Paulo Medical School. Without this mutual collaboration, this important contribution would not be achieved.

“To bring a new, alternative treatment to the medical community is not an easy assignment,” he continued. “This 10-year experience of using PAE confirms that this minimally invasive procedure is not only an alternative for candidates suffering from LUTS due to BPH-enlarged prostates. Several publications from different centres all over the world have shown that PAE has been accepted with excellent results for patients with urinary retention, for BPH-related bleedings, for patients with contraindications to traditional surgical treatments, and for patients with different prostate sizes (small and huge prostates). Now, PAE can be looked at with different eyes. Over the last decade, we have followed every ethical committee approval (local and national) and have followed several lines of inquiry (including investigating different prostate sizes and symptoms, as well as various embolic agent types and sizes). In this Radiology publication, we have included all patients during our ‘learning curve on PAE’. This means that, among all published patients following different prospective trials, we have tested and learned with every single patient and procedure. We were trying to identify the best way to perform PAE. It was really new and challenging to us.”

PAE excluded from urology guidelines globally

In March 2016, the Conselho Federal de Medicina (CFM), the authority in charge of professional regulation and medical licensing in the country, stated that PAE can be used as a new, alternative treatment for symptomatic patients with BPH. However, the board noted that five-year results should be analysed before a final decision is made on the procedure’s inclusion in the national urology guidelines. “Now, after 12 years of PAE and with this 10-year follow-up data, it is time the CFM gives the final approval for PAE,” comments Carnevale. “With that obtained, we hope the Brazilian Urological Society will include PAE in its guidelines for the treatment of BPH.”

This is a global issue. In 2018, results of the UK ROPE study, which compared embolization to conventional prostate surgery, led the National Institute of Health and Care Excellence (NICE) to determine that the evidence on the safety and efficacy of PAE for BPH was adequate to support the use of this procedure on the National Health Service (NHS). They recommended the procedure “provided that standard arrangements are in place for clinical governance, consent and audit”. NICE added: “This technically demanding procedure should only be done by an interventional radiologist with specific training and expertise in PAE”.

Nevertheless, the European Association of Urology (EAU) guidelines for the diagnosis and treatment of men with LUTS/BPH have not been updated, and remain cautious when describing the potential clinical role of PAE. They state: “A multidisciplinary team approach of urologists and radiologists is mandatory as the basis for future randomised controlled trials of good quality with long-term follow-up in order to integrate this treatment option into the spectrum of efficient, minimally invasive treatment options.” Since then, a 2019 study published in European Urology from Tiago Bilhim (Hôpital Saint-Louis, Lisbon, Portugal) et al has demonstrated that improvements in quality of life measurements and IPSS are “far superior” following PAE than due to any placebo effect.

A US Food and Drug Administration (FDA) review in 2017 concluded that “the probable benefits outweigh the probable risks for this indication”, and in June the same year, the indication of Embosphere microspheres (Merit Medical) was expanded through the FDA’s 513(f)(2) de novo classification to include PAE. In 2018, the product was approved for the same indication by a 510(k) pathway. Embozene microspheres (Boston Scientific) also gained an expanded indication in 2018, with the FDA granting approval for its on-label use in PAE treatment in the USA via the 510(k) pathway. However, PAE is not recommended outside of a clinical trial in the American Urological Association (AUA) guidelines, something many interventional radiologists refute.

Addressing doubters of PAE, Carnevale says: “According to the Hippocratic oath, physicians should ‘Apply dietetic measures for the benefit of the sick according to their ability and judgement’. Interventional radiologists have faced turf battles for decades when aiming to bring new alternative treatments for patients. This happened with peripheral angioplasty, fibroid embolization, and abdominal aortic aneurysm repair, among others, and it will not be any different with PAE. We are not saying that PAE is the only or the best treatment for LUTS related to BPH. We have simply brought another option for patients and physicians to discuss. Each treatment has its indications and contraindications, and it is necessary to understand the patient’s aims and wishes. The publication of these exciting results from our 10-year experience of PAE is a great achievement, and should be considered by the medical community. Its time is now.”


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