Editorials
Prostatic Arterial Embolization for LUTS/BPHdAn Opportunity for Collaborative Research or Next Prostatic Gizmo Candidate? LOOKING at a recent trade journal article I noticed this worrisome headline, “PAE May be Safe, Effective for BPH.”1 Imagine my concern upon reading the case report poised as a trial on lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). The problems in this particular preliminary report were numerous and, like every report published so far on this topic, included 1) reliance on imaging based reduction in prostate volume, 2) na€ıve prostato-centric concepts of “BPH,” 3) lack of a control group, 4) unconventional definition of clinical improvement, 5) uniform failure to account for a placebo effect thus leading one to assume that the improvement in LUTS or other outcomes were related to prostatic arterial embolization (PAE) (intervention effect remains unknown), and 6) ignoring LUTS as the motivating complaint and the ultimate arbitrator of success. In particular, when comparing studies that by the nature of the intervention usually do not have a placebo effect (minimally invasive or PAE treatment) with those that use a placebo lead-in, the former treatment will be given full credit for the placebo effect and the true intervention effect, while the latter will be given credit only for the true intervention effect, although for the patient the outcomes may seem the same, ie the same symptom severity level may still be reached! So is the solution the planning of a rigorous trial with well thought out trial design including predefined and well-accepted outcomes and uniform side effect reporting? It should seem simple at first. In March 2013 a multidisciplinary research consensus panel and international collaborative symposium was held among interventional radiologists, urologists, members of industry, attendees from the United States Food and Drug Administration (3 representatives from the Urology and Lithotripsy Devices Branch, and 2 representatives from the Center for Devices and Radiological Health Office of Science and Engineering Laboratories) and the National Institutes of Health (1 representative from Interventional Radiology) to ponder the planning of such a trial. The symposium was organized
0022-5347/14/1913-0577/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
by the Society of Interventional Radiology Foundation as they considered PAE for BPH as an emerging research priority. Drs. J. Kellogg Parsons and Badrinath Konety joined me and others to present background material, disease state data and proposals for a rigorous trial.2 If PAE has merit for our patients there will be no avoiding the truth. However, if PAE is the “balloon dilator of 2014” and thus bound for the trash heap, the best way to expose it with as little risk to our patients and society is through a properly performed randomized clinical trial. The broad range of experts who attended the meeting agreed to author a list of research priorities. The production of this report was a microcosm of the struggles in academic medicine. Examples include 1) the sudden inclusion of a never before mentioned strategic priority item that wanted to preserve the role of interventional radiologists as BPH care providers, 2) inclusion of unpublished material as “evidence of safe and effectiveness of PAE,” 3) submission of a manuscript in which factions were compartmentalized and a first draft article submitted without knowledge of the named authors and, most surprising, 4) discovery that 1 group of investigators presented and attempted to include data from their publications with “extensive overlap.” 3 So what is the outcome and is it still worth participating? As a clinician-investigator I believe that planning collaborations among specialties, scientists, different labs or other diverse groups is the most pleasant of all low hanging fruit in this exciting job that we have been fortunate enough to fall into. Nothing is more full of potential than testing new concepts or mechanisms using a fresh set of eyes. However, as this exercise demonstrates, we must be guarded in our approach and stern about adherence to scientific principle. For now it is critical that urologists remain diligent and unshaken in their willingness to critically evaluate themselves and any others who see PAE as the next new therapy. Until shown otherwise, I believe that academic and organized urology should consider the cautions our colleagues in the Urological Society of Australia
http://dx.doi.org/10.1016/j.juro.2013.12.034 Vol. 191, 577-578, March 2014 Printed in U.S.A.
www.jurology.com
j
577
578
PROSTATIC ARTERIAL EMBOLIZATION
and New Zealand take in their position paper about PAE, which are 1) PAE should only be offered in the setting of an approved clinical trial and should currently be considered experimental, 2) one cannot recommend PAE as a form of management for LUTS/BPH until its safety and efficacy have been better delineated by further studies, and 3) due
to LUTS having multiple causes other than BPH, consultation with a urologist is mandatory before any interventional treatment for BPH including those considering PAE.4 Kevin T. McVary Associate Editor
REFERENCES 1. Charnow JA: Prostatic artery embolization safe, effective for BPH. Renal & Urology News, December 2013. Available at http://www.renalandurologynews. com/prostatic-artery-embolization-safe-effectivefor-bph/article/319433/. Accessed December 17, 2013. 2. Golzarian J, Antunes AA, Bilhim T et al: Prostatic artery embolization to treat lower urinary
symptoms related to benign prostatic hyperplasia and bleeding in prostate cancer patients. In: Proceedings from a Multidisciplinary Research Consensus Panel. 3. Pisco JM, Rio Tinto H, Campos Pinheiro L et al: Erratum to: Embolisation of prostatic arteries as treatment of moderate to severe lower urinary symptoms (LUTS) secondary to benign
hyperplasia: results of short- and mid-term followup. Eur Radiol 2013; 23: 2573. 4. Prostatic arterial embolization for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Available at http://www. usanz.org.au/uploads/29168/ufiles/LUTS_SAG_ Position_Statement_on_PAE_Final.pdf. Accessed December 17, 2013.
Prostatic Arterial Embolization for LUTS/BPHdAn Opportunity for Collaborative Research or Next Prostatic Gizmo Candidate? LOOKING at a recent trade journal article I noticed this worrisome headline, “PAE May be Safe, Effective for BPH.”1 Imagine my concern upon reading the case report poised as a trial on lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). The problems in this particular preliminary report were numerous and, like every report published so far on this topic, included 1) reliance on imaging based reduction in prostate volume, 2) na€ıve prostato-centric concepts of “BPH,” 3) lack of a control group, 4) unconventional definition of clinical improvement, 5) uniform failure to account for a placebo effect thus leading one to assume that the improvement in LUTS or other outcomes were related to prostatic arterial embolization (PAE) (intervention effect remains unknown), and 6) ignoring LUTS as the motivating complaint and the ultimate arbitrator of success. In particular, when comparing studies that by the nature of the intervention usually do not have a placebo effect (minimally invasive or PAE treatment) with those that use a placebo lead-in, the former treatment will be given full credit for the placebo effect and the true intervention effect, while the latter will be given credit only for the true intervention effect, although for the patient the outcomes may seem the same, ie the same symptom severity level may still be reached! So is the solution the planning of a rigorous trial with well thought out trial design including predefined and well-accepted outcomes and uniform side effect reporting? It should seem simple at first. In March 2013 a multidisciplinary research consensus panel and international collaborative symposium was held among interventional radiologists, urologists, members of industry, attendees from the United States Food and Drug Administration (3 representatives from the Urology and Lithotripsy Devices Branch, and 2 representatives from the Center for Devices and Radiological Health Office of Science and Engineering Laboratories) and the National Institutes of Health (1 representative from Interventional Radiology) to ponder the planning of such a trial. The symposium was organized
0022-5347/14/1913-0577/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
by the Society of Interventional Radiology Foundation as they considered PAE for BPH as an emerging research priority. Drs. J. Kellogg Parsons and Badrinath Konety joined me and others to present background material, disease state data and proposals for a rigorous trial.2 If PAE has merit for our patients there will be no avoiding the truth. However, if PAE is the “balloon dilator of 2014” and thus bound for the trash heap, the best way to expose it with as little risk to our patients and society is through a properly performed randomized clinical trial. The broad range of experts who attended the meeting agreed to author a list of research priorities. The production of this report was a microcosm of the struggles in academic medicine. Examples include 1) the sudden inclusion of a never before mentioned strategic priority item that wanted to preserve the role of interventional radiologists as BPH care providers, 2) inclusion of unpublished material as “evidence of safe and effectiveness of PAE,” 3) submission of a manuscript in which factions were compartmentalized and a first draft article submitted without knowledge of the named authors and, most surprising, 4) discovery that 1 group of investigators presented and attempted to include data from their publications with “extensive overlap.” 3 So what is the outcome and is it still worth participating? As a clinician-investigator I believe that planning collaborations among specialties, scientists, different labs or other diverse groups is the most pleasant of all low hanging fruit in this exciting job that we have been fortunate enough to fall into. Nothing is more full of potential than testing new concepts or mechanisms using a fresh set of eyes. However, as this exercise demonstrates, we must be guarded in our approach and stern about adherence to scientific principle. For now it is critical that urologists remain diligent and unshaken in their willingness to critically evaluate themselves and any others who see PAE as the next new therapy. Until shown otherwise, I believe that academic and organized urology should consider the cautions our colleagues in the Urological Society of Australia
http://dx.doi.org/10.1016/j.juro.2013.12.034 Vol. 191, 577-578, March 2014 Printed in U.S.A.
www.jurology.com
j
577
578
PROSTATIC ARTERIAL EMBOLIZATION
and New Zealand take in their position paper about PAE, which are 1) PAE should only be offered in the setting of an approved clinical trial and should currently be considered experimental, 2) one cannot recommend PAE as a form of management for LUTS/BPH until its safety and efficacy have been better delineated by further studies, and 3) due
to LUTS having multiple causes other than BPH, consultation with a urologist is mandatory before any interventional treatment for BPH including those considering PAE.4 Kevin T. McVary Associate Editor
REFERENCES 1. Charnow JA: Prostatic artery embolization safe, effective for BPH. Renal & Urology News, December 2013. Available at http://www.renalandurologynews. com/prostatic-artery-embolization-safe-effectivefor-bph/article/319433/. Accessed December 17, 2013. 2. Golzarian J, Antunes AA, Bilhim T et al: Prostatic artery embolization to treat lower urinary
symptoms related to benign prostatic hyperplasia and bleeding in prostate cancer patients. In: Proceedings from a Multidisciplinary Research Consensus Panel. 3. Pisco JM, Rio Tinto H, Campos Pinheiro L et al: Erratum to: Embolisation of prostatic arteries as treatment of moderate to severe lower urinary symptoms (LUTS) secondary to benign
hyperplasia: results of short- and mid-term followup. Eur Radiol 2013; 23: 2573. 4. Prostatic arterial embolization for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Available at http://www. usanz.org.au/uploads/29168/ufiles/LUTS_SAG_ Position_Statement_on_PAE_Final.pdf. Accessed December 17, 2013.
