24th May 2019 2075
Current evidence supports the use of prostate artery embolization (PAE) as a safe, effective, and minimally-invasive treatment for the symptoms of benign prostatic hyperplasia (BPH) in appropriately selected patients. This is the conclusion of a multisociety consensus position statement on the use of PAE in the treatment of lower urinary tract symptoms attributed to BPH. The document has been published in the May edition of the Journal of Vascular and Interventional Radiology (JVIR) and outlines recommended standards of practice. The multisociety and multidisciplinary position statement comes from the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Société Française de Radiologie (SFR), and the British Society of Interventional Radiology (BSIR).
However, the interventional radiology (IR) community is still working to convince their urology colleagues to adopt the procedure as one treatment option. An SIR-sponsored research consensus panel for PAE has convened with urologists from the American Urological Association (AUA) to map a path towards PAE gaining acceptance in the urologists’ own guidelines. This meeting was chaired by Clifford Davis (Medical College of Virginia, Richmond, USA) and Jafar Golzarian (University of Minnesota, Minneapolis, USA). Golzarian informed Interventional News that one of the key takeaways from this meeting was understanding the importance urologists place on sham studies. Currently, a study comparing PAE with a sham procedure is underway; many in the IR community are hopeful that the publication of this data will support their case for the recognition of PAE as an effective, minimally-invasive procedure by urologists.
The recommendations of the multisociety consensus position statement
The multisociety release, penned by Justin McWilliams (David Geffen School of Medicine, Los Angeles, USA) et al, advises PAE be used as a “valuable minimally invasive option for patients who cannot tolerate or who have failed medical therapy, and those who are poor surgical candidates or refuse invasive surgery.” The document makes the following eight recommendations:
- PAE is an acceptable minimally invasive treatment option for appropriately selected men with BPH and moderate to severe lower urinary tract symptoms.
- PAE can be considered as a treatment option in patients with BPH and moderate to severe lower urinary tract symptoms who have very large prostate glands (>80cm3), without an upper limit of prostate size.
- PAE can be considered as a treatment option in patients with BPH and acute or chronic urinary retention in the setting of preserved bladder function as a method of achieving catheter independence.
- PAE can be considered as a treatment option in patients with BPH and moderate to severe lower urinary tract symptoms who wish to preserve erectile and/or ejaculatory function.
- PAE can be considered in patients with haematuria of prostatic origin as a method of achieving cessation of bleeding.
- PAE can be considered as a treatment option in patients with BPH and moderate to severe lower urinary tract symptoms who are deemed not to be surgical candidates for any of the following reasons: advanced age, multiple comorbidities, coagulopathy, or inability to stop anticoagulation or antiplatelet therapy.
- PAE should be included in the individualised patient-centred discussion regarding treatment option for BPH with lower urinary tract symptoms.
- Interventional radiologists, given their knowledge of arterial anatomy, advanced microcatheter techniques, and expertise in embolization procedures, are the specialists best suited for the performance of PAE.
In addition to the four societies that authored the guidelines, these recommendations are endorsed by the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR), the Canadian Association for Interventional Radiology (CAIR), the Chinese College of Interventionalists, the Interventional Radiology Society of Australasia, the Japanese Society of Interventional Radiology, and the Korean Society of Interventional Radiology.
Speaking recently at GEST (Global Embolization Oncology Symposium Technologies; 9–12 May, New York, USA), lead author Justin McWilliams addressed the audience on the status of international recommendations for PAE. “These recommendations are very supportive of PAE, and I think are reflective of the data and literature that are currently out there. With the endorsement of multiple international IR societies, my co-authors and I reviewed all articles published between 2010 and 2018 relevant to PAE—some 280 articles, which were whittled down to 67 after duplicate cohort, case reports and technical papers were excluded—and summarised their findings.” Of the 67 included articles, three were randomised controlled trials, a further three were non-randomised comparative trials, and 17 were unique cohort studies. There were also multiple reviews and meta-analyses, in addition to miscellaneous papers focusing on factors such as cost and radiation exposure. In total, over 2,200 patients from eleven countries were reviewed in these studies.
“The overall findings were of no surprise to anyone in this room”, McWilliams said to the attendees of the GEST PAE Symposium, all interventional radiologists, “and are similar to the findings of prior meta-analyses. PAE is definitely effective; IPSS [International Prostate Symptom Score] improvement, depending on which study you look at, is between 10 and 18 points, and quality of life improvement ranges from two to four points. Just as importantly, PAE is very safe, with a low major complication rate and no change in erectile function. Ejaculatory dysfunction is still an open question; that was originally thought to be very uncommon, but some more recent studies have shown higher than expected rates of either reduced ejaculation or dry ejaculation. Radiation dose seems to be similar to other complex embolizations, such as gastrointestinal haemorrhage or pelvic arteriovenous malformation embolization. In certain specific clinical scenarios, PAE is also effective. Definitely so in very large prostates, and catheter independence can be achieved in approximately 80% of patients with a Foley catheter. Haematuria of prostatic origin can almost always be stopped immediately.”
Calling this “a landmark document”, Marc Sapoval (Hôpital Européen Georges-Pompidou, Paris, France), a co-author of the statement, voices his support to this newspaper: “At this point in 2019, we can say that PAE can be used safely and effectively in patients as an alternative to other treatments. This is strongly stated and supported by IR societies all around the world. I think this is very important for IR, to give us confidence in our support of PAE.”
Speaking to Interventional News of the importance of these guidelines, Sandeep Bagla (Vascular Institute at Virginia, Woodbridge, USA), a co-author of the document, says: “We as a community are proud to have seen these guidelines come to fruition, after many years of having our initial guidelines out. It is a very difficult and tedious process to update a position statement. Along with many other important co-authors, including lead author Justin McWilliams, who really was the energiser behind this project, we were able to pull together a collaborative document representing the evidence-based view of many societies around the world. The value of this document is multi-fold. It is a rather big step for SIR to put forth this document with recommendations; it mirrors the actions of other large societies, such as the American Heart Association, where the guidelines are presented in a similar manner, based on level of evidence and the strength of recommendation. That is important, because many guidance documents just release recommendations based on panel agreement, not based on a review of data, and without using a universally accepted grading system, like we do in these recommendations.”
History of benign prostatic hyperplasia treatment recommendations
Prostate artery embolization is a minimally-invasive treatment for lower urinary tract symptoms attributed to BPH. More than 70% of men aged over 70 are affected by BPH, and a quarter of men over 70 have moderate to severe lower urinary tract symptoms that impair their quality of life. This has led McWilliams et al to call BPH and ensuing lower urinary tract symptoms a “significant health issue affecting millions of men”.
The lower urinary tract symptoms caused by BPH have historically been treated by medical and surgical methods. Medical therapies, such as α-1 blockers and 5-α reductase inhibitors, are the mainstay of treatment for mild to moderate lower urinary tract symptoms, while the more invasive transurethral resection of the prostate (TURP) and simple prostatectomy are considered the gold standards for patients with severe symptoms.
After initial reports on PAE in humans from João Pisco (Lisbon, Portugal) and Francisco Carnevale (University of Sao Paulo Medical School, Sao Paulo, Brazil), McWilliams described the AUA as “unimpressed”, after their 2010 guidelines for the management of BPH failed to mention PAE. An initial review by the UK National Institute for Care Excellence (NICE) concluded in 2013 that more research was needed to establish the safety and efficacy of the procedure. McWilliams authored an initial SIR position statement in 2014, with multiple other interventional radiologists, though he says that “at that time, the data was not yet mature. We also concluded that additional investigation was needed before we could accept PAE into routine therapy.”
However, “a lot has changed over the last five years”, he says. To date, more than 2,000 patients have been studied in PAE-pertaining publications, and there have been three randomized controlled trials comparing PAE to TURP. The longest duration of follow-up now exceeds five years. An 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 US FDA granting approval for its on-label use in PAE treatment in the USA via the 510(k) pathway.
In the UK, NICE determined last year 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). This decision came after BSIR and the British Association of Urological Surgeons (BAUS) worked together to coordinate the UK ROPE study. The study compared embolization to conventional prostate surgery. It found embolization provided a clinically and statistically significant improvement in symptoms and quality of life for men with an enlarged prostate.
Also last year, in the USA, the updated AUA guidelines briefly mentioned PAE, where they did not recommend the procedure’s use outside of a clinical trial. During a debate at GEST on the topic this May, no one in attendance said they thought PAE should be restricted to clinical trials only. Indeed, during the PAE Symposium hosted by the conference, Riad Salem (Northwestern University, Chicago, USA), another co-author of these multisociety guidelines, said that, with the FDA approval of the Embosphere and Embozene microspheres, interventional radiologists “should not assume that PAE can only be performed as part of a clinical trial. In fact,” he added, “most cases are not. I think that is an important nuance.” However, he also said that “the most powerful data you can generate for your institution is the data generated internally”, and urged any audience members who performed PAE to collect data from their own patients. This is something done by an interventional radiologist attending the GEST PAE Symposium, who shared that he contacts all of his PAE patients one, three, six and 12 months post procedure.
In the most recent guidelines from 2018, the AUA calls for additional sham trials to account for a possible placebo effect, and, in McWilliams’ words, “remain unconvinced of the efficacy and safety of the technique”. Tiago Bilhim announced that he is working on a study that will compare PAE against a sham procedure and that he hopes for the results to be published later this year. This work was started with his colleague Pisco, who passed away in March this year.
“We will have a lot more success if we collaborate with urology”
As NICE approved PAE in the UK in 2018, Tarun Sabharwal (Guy’s and St Thomas’ Hospital, London, UK), a co-author of the guidelines and a GEST panellist, says that the collaboration between urologists and interventional radiologists in Britain acts as an example of how this relationship can benefit patients. He tells this newspaper: “These guidelines are significant in that they highlight to the American urological community what interventional radiologists can safely offer. Currently in the UK, with NICE approval for PAE, we have a good collaboration between urology and IR. We are able to offer our patients a broad spectrum of choices for their prostate outlet obstructions that include embolization, so it is an alternative to surgery for them.”
“For me, the issue I have with this therapy is that the response I get from urology is not a scientific response, it is an emotional response,” Salem tells the GEST audience during the PAE Symposium, speaking of the reaction he sees from urologists to PAE. “Even when you highlight the limitations of current therapies for BPH, and you highlight the tremendous work that has been done over the last ten years on PAE, the calibre of new studies that are being performed, the robustness of the findings, the attempts to recognise what you can and cannot do in a randomised setting, the post-hoc analyses, independent analyses by NICE—all the data triangulate to their being an important role for PAE in BPH. I think we have to get away from the emotionality of the subject.”
This sentiment is echoed by Marc Sapoval (Hôpital Européen Georges-Pompidou, Paris, France) and Golzarian, also authors of these recommendations. Speaking to Interventional News, Sapoval comments: “I think this document demonstrates to urologists that IR is organised as an international community, and has an academic rigour equal to that of other specialties. We are taking PAE seriously, because we believe the evidence points to the procedure as a safe and effective one. I do not believe urologists are taking us seriously at this point, though I hope that changes—it is the patients who are currently missing out.”
Golzarian adds, “PAE clearly works and helps patients—it is here to stay. In my opinion, the urologists’ guidelines are biased; they are mostly led by a few urologists that are personally very involved with urologic material development for BPH. Despite asking persistently, there was also no involvement of any IR society in the making of these guidelines [the most recent AUA guidelines, from 2018]. My strong recommendation is that SIR and AUA work hand-in-hand to identify which patients will benefit most from PAE. As a physician, our goal should only be to provide the best care for our patients; anything else is secondary.”
Understanding the demand from the IR community for a closer collaboration with urology, one interventional radiologist who recently met with the AUA describes this conversation: “What we discussed was the lack of level I evidence, [which is needed] for any therapy to make it into the guidelines. I think they [AUA] have a very strong stance on this. Having said that, they are not very rigid in terms of their guidelines, because, for example, they are flexible in using bipolar TURP or using GreenLight laser for large glands, which is not what the guidelines state. The guidelines only state [you should use] monopolar TURP or perform open prostatectomy, but that is not the standard of practice.
“However, we do have a SIR [multisociety] position statement, which details when to use this procedure [PAE] in specific settings, but PAE is not in the AUA guidelines. The AUA guidelines are important in terms of reimbursement for the procedure.” Insurance coverage for PAE currently varies across the USA.
In order to convince urologists that interventional radiologists are knowledgeable and skilled when it comes to PAE, Insausti Gorbea (Clínica Universidad de Navarra, Navarra, Spain), a panelist at the PAE Symposium hosted by GEST, stressed how important he believed it was to select patients carefully, saying “I think trials now should not be comparing PAE to surgery or TURP any longer; trials should be just to find out who are the good responders to this treatment. I think the technique is mature enough for this. Then we can say to urologists, ‘I know my limits’.” This comment was met with agreement by Bilhim, who added that for those first starting out performing PAE, they should begin with straightforward cases. Also in accordance, an audience member commented: “It does take some experience, so you should have five to seven years’ experience with basic embolization before moving on to PAE.”
Fonte: Interventional News