Editorial: Prostatic Artery Embolization: Adding to the arsenal against the hapless prostate.
Ever since Hugh Hampton Young introduced the cold punch method in 1909 for ‘punching out’ pieces of the prostate through a modified urethroscope, urologists have used a bewildering array of technology and methods to wage war against the hapless prostate. Methods in the current arsenal include ‘heat and kill’ (transurethral needle ablation, transurethral microwave therapy and Rezum treatment), ‘freeze and kill’ (cryotherapy), ‘slice’ (transurethral incision of prostate), ‘dice’ (transurethral resection of prostate [TURP]), ‘eviscerate and leave the prostate a shell of its former self’ (open prostatectomy and holmium laser enucleation of prostate), ‘suspend and open’ (Urolift), ‘poison’ (intraprostatic injections with Botox, alcohol and NX 1207), ‘vaporize’ (photoselective vaporization of the prostate [PVP]) and, if the prostate dares to turn cancerous, then we just cut it out with scalpels or robots. For the best Botox treatment baytown do follow us. Prostatic artery embolization (PAE) adds to our already impressive armamentarium via a technique similar to strangulation by blocking arterial flow and essentially causing prostatic infarction. PAE also brings a member of another medical discipline to the frontline: the radiologist.
In this issue of BJUI, Müllhaupt et al. [1] report an in-hospital cost analysis of PAE compared to TURP, in their post hoc analysis of a randomized controlled trial. Treatment costs are an important component of healthcare but are a narrow and focused view of the overall management of BPH in an individual patient. The authors report that the in-hospital costs for PAE and TURP are similar and, therefore, cost should not be a consideration when deciding between PAE and TURP. Interestingly, the main procedural costs for TURP were anaesthesia, and the main cost factor for PAE was medical supplies. The urologist and radiologist physician charges were ~13% and ~15% of the procedural costs, respectively. So, if the costs of PAE and TURP are similar, how do you assess which to use?
The article by Müllhaupt et al. should be read in conjunction with other papers describing the efficacy, safety and outcomes of PAE compared to TURP, especially the original article by Abt et al. [2] from which this cost analysis is derived and the UK-ROPE study by Ray et al. [3].
Historically, prostatic infarction is known to be a possible result of cross-clamping the aorta for coronary or aortic surgery, hypotensive myocardial infarction or septic shock. PAE is an iatrogenic cause of prostatic infarction. In 1947, Wilbur G. Rogers [7], in ‘Infarct of the Prostate’, documented that ‘There is first swelling of the area involved, with degeneration and necrosis of the cells. This may be followed by absorption of the damaged area and fibrosis and cicatrization of the parts so that eventually the volume is much less than it was originally’. This is one of the early descriptions of how PAE potentially works.
Prostatic artery embolization as a technique is feasible and has been shown to be relatively safe and efficacious in certain specialized institutions, as shown by the UK-ROPE study [3] and by Abt et al. [2]. It should be noted that PAE can be a technically challenging procedure and, although bilateral embolization is the goal, only unilateral embolization is possible in 25% of cases [1]. Highly specialized training is required, and the technique continues to evolve to avoid embolization of extraprostatic branches [3]. PAE is more painful than TURP, with higher reported pain on a visual analogue scale and higher analgesic use [2], but is associated with a shorter length of hospital stay [1,2]. PAE is reported to be associated with an earlier return to normal activities but is less effective than TURP at 12 weeks with regard to changes in maximum rate of urinary flow, postvoid residual urine, prostate volume and desobstructive effectiveness according to pressure flow studies [2] and has a 20% reoperation rate after 12 months [3].
There are still some questions and issues surrounding PAE that may eventually be addressed with time and further studies. Embolizing an artery causes cell death and necrosis and eventual atrophy. This process is uncontrolled, however, and unpredictable in any individual patient. There is no way to know how much tissue or which part of the prostate is going to infarct and undergo necrosis with unilateral or bilateral embolization. If or when a potential abscess forms has not been defined or studied.
The longer-term effects of radiation dosage for PAE will not be known for many years. In the Abt et al. study cohort [2], the radiation dose (dose area product [DAP]) was 176.5 Gy/cm2. A standard anteroposterior and lateral chest X-ray exposes the patient to 0.3 Gy/cm2. An abdominal CT scan exposes the patient to ~32 Gy/cm2. PAE is thus roughly equivalent to ~5–10 standard abdominal/pelvic CT scans (more if using ultra-low dose scanners), 586 chest X-rays, 4.4 barium enemas or 8.8 voiding cysto-urethrograms. Markar et al. [4] reported that there was a significant increase in abdominal cancer within the radiation field in 14 150 patients undergoing endovascular aneurysm repair (EVAR), with 18% of patients who underwent EVAR succumbing to cancer. The mean radiation exposure (or DAP) in a review of 24 studies on EVAR [5] was 79.48 Gy/cm2, which is approximately half the radiation exposure of PAE.
Müllhaupt et al. [1] showed that PAE was associated with a quicker return to normal activities and a shorter length of stay than TURP, with similar in-hospital costs in Switzerland. Cost, however, must be considered alongside safety and efficacy data both in the short and long term. It is important to appreciate the specialized and technical expertise required to safely perform PAE and the importance of a urologist being part of the multidisciplinary management team as recommended in the National Institute for Health and Care Excellence (NICE) guidelines [6] (IPG611 April 2018). Radiation exposure will need close scrutiny and detailed reporting to document long-term effects, as demonstrated in the EVAR trials. Radiation dosage is cumulative over a lifetime and this must be considered when other interventional radiological procedures such as coronary angiograms and positron-emission tomography/CT are becoming more common. PAE should be compared with other emerging minimally invasive BPH procedures such as Urolift and Rezum in future studies, instead of just TURP to determine its role in BPH management and whether the radiation dose is justified. Longer-term studies are needed to assess the costs of managing any long-term
complications, re-operation rates and longer-term efficacy associated with PAE.
by Peter Chin
South Coast Urology, Wollongong, NSW, Australia
References
- Müllhaupt G, Hechelhammer L, Engeler D et al. In-Hospital cost analysis of prostatic artery embolization compared to transurethral resection of the prostate: post hoc analysis of a randomized controlled trial. BJU Int 2019;123: 1055-60
- Abt D, Hechelhammer L, Müllhaupt G et al. Comparison of prostatic artery embolization (PAE) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia: randomized, open label, noninferiority trial. BMJ 2018; 361: k2338
- Ray AF, Powell J, Speakman MJ et al. Efficacy and safety of prostate artery embolization for benign prostatic hyperplasia: an observational study and propensity-matched comparison with transurethral resection of the prostate (the UK-ROPE study). BJU Int 2018; 122: 270–82
- Markar SR, Vidal-Diez A, Sounderajah V et al. A population-based cohort study examining the risk of abdominal cancer after endovascular abdominal aortic aneurysm repair. J Vasc Surg 2018; Article in Press. https://doi.org/10.1016/j.jvs.2018.09.058 [Epub ahead of print]
- Monastiriotis S, Comito M, Lapropoulos N. Radiation exposure in endovascular repair of abdominal and thoracic aortic aneurysms. J Vasc Surg 2015; 62: 753–61
- NICE Guidance. Prostate artery embolisation for lower urinary tract symptoms caused by benign prostatic hyperplasia. BJU Int 2018; 121: 825–34
- Rogers WG. Infarct of the prostate. J Urol 1947; 57: 484–7
I am a patient who was the first PAE case at the Prostate Centre (June 2017) and I refer to the details of my case already published in the BJUI as a comment on the ROPE study by Professor Michael Kirby and myself, to which I provide a link here.
The comment I want to make on this excellent Editorial is that I think one has to be careful when one assesses the radiation exposure in PAE to recognise that, in some patients, such as my own case, the CT angiogram which is done before the PAE shows easy and rapid access to the prostatic artery for the procedure, and in some cases it may show more difficult or complex vascular anatomy, so that access is more difficult and the PAE will take more time to carry out. Thus, radiation exposure may be quite different for individual patients. It may just be a matter of wording, but I don’t think it is quite accurate to talk in the Editorial in terms of “PAE is therefore roughly equivalent to ….” and give a radiation dose or equivalents, because it all depends on the individual circumstances.
In the UK-ROPE cohort, the median screening time was 38 minutes with a median dose area product of 17,892 cGy•cm2 and median skin dose of 1,368 mGy and this equates to 44 mSv. I refer to another very good article published in the journal “Endovascular Today” (April 2019) by Dr Timothy J Bryant. Dr Bryant cites references to the literature which – Dr Bryant says – show that a dose of 44 mSv equates to a 0.17% additional lifetime cancer risk in the case of a 50- to 59-year-old man, compared with the estimated lifetime risk of a cancer diagnosis of 1 in 2 (50%) for men in the general population. I attach a link to Dr Bryant’s article.
In my own case, my angiogram showed that access to the prostatic artery could be rapid. Before the PAE I was provided with an estimated typical dose of 40 mSv, but in fact access during the PAE was so rapid that, after the PAE, I was told that the dose had in fact turned out to be only a quarter of that. If this is right, it shows that radiation dosage may be a highly individual matter.
When evaluating the radiation risk, say in the context of a patient considering a PAE versus a HoLEP or a TURP, it is in my view, fair to balance the radiation risk of PAE against the risk of a stoke or pulmonary embolism during HoLEP or TURP, as given by BAUS (April 2017) said to be between 1/50 and 1/250.
It only remains to add that that this Editorial by Dr Chin is a commendable, excellent and very helpful addition to the literature/discussion on PAE.
I have had a PAE performed recently and, so far, after 5 weeks, it has not gone well. I went into acute urinary retention within 48 hours and have been catheterized since then. I’ve been frantically researching literature to try and get a handle on it. The radiation risk had not occurred to me until today, so I don’t know what my personal exposure was. I am now awaiting a follow-up TURP procedure ASAP and my long-time urologist is a bit pissed at me for not doing it in the first place – as am I.
Needless to say, when I read “with 18% of patients who underwent EVAR succumbing to cancer” I totally freaked out. So, I went to look at the referenced study (Markar SR, Vidal-Diez A, Sounderajah V et al.) and saw that the results are expressed as a “hazard risk” (HR).
HR for abdominal cancer, according to the study was calculated at 1.14 indicating a 14% higher risk in the EVAR group. To put it another way, for every 100 patients in the AAA repair (control) group who succumbed to abdominal cancer, their were 114 patients in the EVAR group who succumbed. The HR range was 1.03 – 1.27.
Another way of looking at it: While 18% of EVAR patients succumbed to cancer during the 7-year follow-up period, 15.8% of the AAA-repair did so as well. Looking at it that way, it is a bit less alarming; in retrospect, however, I would not elect to undergo PAE again.