Prostatic Arterial Embolization: Post-Procedural Follow-up

Prostatic Arterial Embolization: Post-Procedural Follow-up Lucia Fernandes, MD,* Hugo Rio Tinto, MD,* Jose Pereira, MD,* Marisa Duarte, MD,* Tiago Bilhim, MD, PhD,*,† and Joa~ o Martins Pisco, MD, PhD* Prostatic arterial embolization (PAE) gained special attention in the past years as a potential minimally invasive technique for benign prostatic hyperplasia. Treatment decisions are based on morbidity and quality-of-life issues and the patient has a central role in decision-making. Medical therapy is a first-line treatment option and surgery is usually performed to improve symptoms and decrease the progression of disease in patients who develop complications or who have inadequately controlled symptoms on medical treatment. The use of validated questionnaires to assess disease severity and sexual function, uroflowmetry studies, prostate-specific antigen and prostate volume measurements are essential when evaluating patients before PAE and to evaluate response to treatment. PAE may be performed safely with minimal morbidity and without associated mortality. The minimally invasive nature of the technique inducing a significant improvement in symptom severity associated with prostate volume reduction and a slight improvement in the sexual function are major advantages. However, as with other surgical therapies for benign prostatic hyperplasia, up to 15% of patients fail to show improvement significantly after PAE, and there is a modest improvement of the peak urinary flow. Tech Vasc Interventional Rad 15:294-299 C 2012 Elsevier Inc. All rights reserved. KEYWORDS prostatic arterial embolization (PAE), benign prostatic hyperplasia (BPH)

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enign prostatic hyperplasia (BPH) has a high prevalence rate in men aged 50-79 years, being ubiquitous with aging. BPH is a condition often associated with lower urinary tract symptoms (LUTS), such as decreased urinary stream, higher urinary frequency, and urinary urgency.1-4 Medical therapy is a first-line treatment option and surgery is usually performed to improve symptoms and decrease progression of disease in patients who develop complications or who have inadequately controlled symptoms on medical treatment.5 Although both medical and surgical treatment options for BPH are effective, they are associated with high morbidity rates. Thus, there is the need for innovative

*Interventional Radiology Department, Saint Louis Hospital, Lisbon, Portugal. †Anatomy Department, Radiology Department, Faculdade de Ciˆencias Me´dicas, Universidade Nova de Lisboa, Lisbon, Portugal. Address reprint requests to: Lucia Fernandes, MD, Interventional Radiology Department, Saint Louis Hospital. Rua Luz Soriano, no. 182, 1200-249 Lisbon, Portugal. E-mail: luci_fernandes@ hotmail.com

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technologies to continue to improve outcomes and minimize patient discomfort and morbidity when managing BPH.6 Prostatic arterial embolization (PAE) for BPH has been shown to be safe and effective inducing prostatic volume reduction in animals7,8 and humans.9,10 For patients who indicate their symptoms to be especially troublesome, or in whom pharmacological management has produced suboptimal results, uroflowmetry measuring the peak urinary flow rate (Qmax) and the postvoid residual volume (PVR) may be warranted. Qmax and PVR give useful information on mictuation, and the results can be used to assess severity of obstruction, predict the likelihood of disease progression and response to treatment.11 We started to use PAE as an alternative treatment option for patients with severe symptomatic LUTS due to BPH in 2009, and have performed over 262 procedures to the present date. In appropriately selected patients, the mean procedure time is approximately 90 minutes with a mean 30 minutes of fluoroscopy. All patients are evaluated by clinical observation with measurement of the International Prostate Symptom

1089-2516/$ - see front matter & 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.tvir.2012.09.008

Postprocedural follow-up of PAE Score (IPSS) and quality of life (QOL)–related symptoms, International Index of Erectile Function (IIEF); uroflowmetry (Qmax and PVR), serum prostate-specific antigen (PSA) level, and transrectal ultrasound (TRUS) to calculate prostatic volume as previously explained in the article ‘‘Work up of BPH patient’’. Baseline data is obtained before PAE, and we usually measure response to treatment at 1 month, 3 months, 6 months, and every 6 months after the procedure.12

Imaging Evaluation TRUS is performed in every patient before and after PAE to evaluate prostate volume. Prostate volume measurement by TRUS may vary when patients have large prostates or observers have varying levels of experience.13 We also evaluate prostate volume, structural changes and perfusion by magnetic resonance (MR) before and 15 days-6 months after PAE in some patients. The prostate diameters are visually measured by TRUS (Fig. 1) and MR (Fig. 2) on the 3 plane axes: sagittal, cephalocaudal, and transverse. Volumes are assessed with the following ellipsoid formula: p/6  (transverse diameter  anteroposterior diameter  cephalocaudal diameter). One observer performs all TRUS examinations and another performs all MR examinations (2 experienced radiologists) with the use of these measurement techniques and volume formulas, before and after PAE, to avoid interobserver variability. In some patients, the MR postcontrast images showed a central area of nonenhancing tissue, because of PAE-induced prostatic ischemia (Fig. 3).

Prostatic MR Imaging Interpretation For the selection and follow-up of our patients, besides the PAE aspects already described, we also used MR

295 imaging (MRI) to exclude other prostatic diseases like prostatic cancer. T2-weighted imaging (T2WI) provides the best depiction of the prostate’s zonal anatomy and capsule. T2WI is used for prostate cancer detection, localization, and staging. Prostate cancer typically manifests as a round or ill-defined, low-signal-intensity focus in the peripheral zone. T2WI alone is sensitive but not specific for prostate cancer and should be improved using functional techniques.14 Dynamic contrast enhanced MRI following the administration of gadolinium-based contrast medium is the most common imaging method for evaluating prostate vascularity.15 Normal prostate is highly vascular, a comparison of pregadolinium and postgadolinium images is used to discern prostate necrosis after PAE.12 Dynamic contrast enhanced MRI consists of a series of axial T1WI gradient echo sequences covering the entire prostate during and after IV bolus injection (2-4 mL/s) of gadolinium-based contrast medium.16,17 Diffusion weighted imaging is a powerful clinical tool, as it allows apparent diffusion coefficient (ADC) maps to be calculated, enabling qualitative and quantitative assessment of prostate cancer aggressiveness. Cancer shows a lower ADC value than normal prostate tissue. Furthermore, ADC values correlate with Gleason scores.18,19 MR spectroscopic imaging is able to show the lower levels of citrate and higher levels of choline of prostate cancer compared with benign tissue.20

Clinical Evaluation The IPSS is a validated questionnaire that is a simple and reliable method to assess the presence, type, and severity of symptoms and the response to treatment. It is a set of 7 questions (each scored from 0 to 5) regarding incomplete emptying, micturation frequency, intermittence, urgency episodes, weak urinary stream, straining at urination, and nocturia. The questionnaire yields a total

Figure 1 Prostate volume assessment by TRUS. (A,B) Before embolization, length 66.4 mm, width 64.4 mm, height 53.9 mm, and volume 121 mL. (C,D) One week after embolization, length 64.2 mm, width 61.3 mm, height 51.5 mm, and volume 106 mL; 12,4% reduction. (Color version of figure is available online.)

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Figure 2 Prostate volume assessment by pelvic MRI. (A) Axial T2-weighted image before PAE. Prostate transverse diameter of 50 mm. (B) Sagittal T2-weighted image before PAE. Prostate cephalocaudal diameter of 67 mm and anteroposterior diameter of 41 mm, with total prostatic volume of 71 mL. (C) Axial T2-weighted image 18 days after PAE shows prostate transverse diameter of 45 mm. (D) Sagittal axial T2-weighted image 18 days after PAE shows a prostate cephalocaudal diameter of 63 mm and anteroposterior diameter of 41 mm, with total prostatic volume of 60 mL; a decrease of 15,5%. (Color version of figure is available online.)

Figure 3 Pelvic MR images with contrast in a patient with BPH before (top row) and after PAE (bottom row) to show prostatic ischemia after the procedure.

Postprocedural follow-up of PAE score ranging from 0 to 35 (1-7 for mild symptoms, 8-19 for moderate, and 20-35 for severe). One additional question (about how men feel about their current urinary symptoms) yields a score for QOL (0, delighted; 6, terrible). The response on the QOL question is a strong predictor for patient management.21 Sexual dysfunction is frequently associated with BPH and may also occur after treatment. Evaluation of sexual function can be assessed with the IIEF, a widely used, multidimensional, self-reporting instrument that has been recommended as a primary endpoint for clinical trials and for diagnostic evaluation of erectile dysfunction severity.22 It should be assessed before and after treatment to ensure that no treatment-related sexual dysfunction occurs. The preservation of sexual function and the minimally invasive and nonsurgical nature of this procedure are great advantages.

297 reduction have major symptom improvement whereas others with significant prostatic volume reduction fail to show improvement clinically. However, patients with clinical success have greater prostate volume and PSA reductions, associated with a higher Qmax than those who fail to improve significantly. Prostate volume and acute urinary retention before PAE do not seem to influence clinical results. Extensive atherosclerotic lesions in the iliac and prostatic arteries leading to suboptimal technical results (with unilateral or subselective embolization) are associated with worse clinical results. Also, up to a quarter of patients may have clinical failure after PAE. This is not surprising as there is a clinical failure rate of 10%-30% after conventional open prostatic surgery or TURP, mostly due to detrusor underactivity, which is thought to be one of the important causes of a less favorable outcome after TURP.11

Uroflowmetry Evaluation Objective measurement of uroflowmetry variables such as Qmax and PVR gives useful information on micturition, and the results can be used to assess the severity of obstruction and predict the likelihood of disease progression and response to treatment. The normal Qmax in a young healthy adult male is around 25 mL/s, while in a patient with BPH, there is a weaker stream, more stable due to urethral compression. When the Qmax measured by uroflowmetry is below 12 mL/s, generally it is indicative of obstruction (caused by BPH in the majority of cases).17 Large PVR urine volumes (above 200 mL) may indicate bladder dysfunction. Further examinations, such as pressure flow or videourodynamic studies, may be used in selected patients. From our data there is a mean decrease of the IPSS of 11 points, an improvement of the QOL of 1.5 points, a mean Qmax increase between 3.1 mL/s and 4.4 mL/s and a mean improvement of the IIEF of 2.1 points with a mean prostate volume reduction between 20% and 30% and of the PSA of around 30%. These results are better than the ones obtained with medical therapies. The clinical improvement evaluated by the IPSS is similar to the ones evaluated by other minimally invasive techniques such as transurethral microwave thermotherapy and transurethral needle ablation, and slightly lower than the ones obtained with transurethral resection of the prostate (TURP). The improvement of the Qmax is lower than those obtained by other surgical techniques. This is not surprising as this is a technique that does not remove prostatic tissue. It is still not clear if the clinical benefit relies only on the prostatic volume reduction of 20%-30% or on prostatic glandular tissue remodeling due to ischemia, necrosis, and fibrosis with possible destruction of muscular tissue (decreasing the tonus and contraction around the urethra) and neuronal receptors (decreasing the sensation of obstruction felt by the patient). This might explain why some patients with minor prostatic volume

PSA Evaluation The serum PSA test is an indicated laboratory test that has an excellent correlation with prostate size and helps predict the natural history of the condition. Assessing prostate volume by digital rectal examinationor TRUS, or both is also usually performed. These examinations help assessing the probability of disease progression (high risk patients) and of prostatic cancer guiding the eventual need for prostatic biopsy.19

Intraprocedural and Postprocedural Results During PAE, patients usually report light or no pain at all and sometimes a burning sensation in the urethra, near the rectum and anus. If severe pain develops, one should suspect a complication. After PAE, there are minimal postembolization symptoms and most patients report light or no pain at all. Fever or vomiting is also never present. Generally, there is a good and immediate recovery. We consider technical success when selective prostatic arterial catheterization and embolization is achieved at least on 1 pelvic side because in up to 20% of patients anastomoses can be seen to contralateral prostatic arteries and because up to 50% of patients have significant clinical improvement even after unilateral embolization. In contrast to uterine artery embolization, we noted minimal postembolization symptoms in our study patients. The anti-inflammatory drugs used before, during, and after PAE may be enough to prevent possible embolization related symptoms. We consider poor outcome after PAE when 1 of the following criteria is met: IPSS Z20 or reduction o25% or both; QOL Z4 or reduction o1 or both; Qmax improvement o2.5 mL/s; additional treatments required.12

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First Week Following PAE All patients stop prostatic medication 2 weeks before the PAE and stay without any prostatic medication after the procedure. In those patients under urinary retention before the PAE procedure the vesical catheter is usually removed 15-45 days after PAE. We usually advise to remove the bladder catheter 15 days after PAE, but some patients remain with retention at that time and may only be able to remove the catheter 30-45 days after PAE. In those cases we also recommend trying prostatic medication with alpha-adrenergic antagonists to facilitate the catheter removal. Almost all patients can then successfully urinate spontaneously without the need of prolonged catheterization and without relapsing episodes of urinary retention. In the first weeks, many patients experience some difficulty in urinating that may be due to local inflammatory changes and due to the fact that they stopped all prostatic medication. That problem is usually solved in the first 4 weeks. Those patients who experience extreme difficulty in urinating in the first weeks or who persist with severe symptoms after PAE are counseled to resume the pre-PAE prostatic medication. From our experience, minor complications such as urinary tract infection, balano-prostatitis, hematuria, and hematospermia may occur in a minority of patients in the first weeks following PAE. However these are all selflimited episodes that resolve spontaneously with conservative and medical care. We believe this is probably due to migration of some PVA particles through the anastomoses between the prostatic and the neighboring arteries. The profound ischemia induced in the prostate and urethra may also render the lower urinary tract vulnerable to infection, so we usually advice the patients to avoid sexual intercourse in the week following the procedure. We had only 1 major complication in our series. One patient had partial ischemia of the bladder wall due to a proximal and aggressive embolization of both prostatic and vesical arteries. He was treated with surgical removal of intravesical debris but bladder wall repair was not necessary. When catheterizing the anterior-lateral prostatic pedicles, one should avoid the vesical branches, and when one is embolizing the posterior-lateral prostatic pedicles, the rectal branches (if present) should be avoided. If a major vesical or rectal branch is identified the microcatheter should be advanced distally to spare these arteries. From our experience the migration of PVA particles through tiny anastomoses does not cause major clinical complications when a slow controlled infusion is used. Thus, the presence of small anastomoses to neighboring arterial systems should not prohibit embolization.

First 6 Months After PAE The clinical improvement after PAE is not predictable, and up to 10%-15% of patients may have poor outcome after PAE. Prostate volume reduction does not correlate

with clinical outcome as patients with similar prostate volume reductions may have completely different outcomes.12 Patients may experience prostate volume reduction without clinical improvement; and patients with stable or even increased prostate volume may have clinical improvement. The poor correlation between prostatic volume reduction and clinical outcome implies that prostatic volume reduction might not be the only mechanism that allows symptom improvement after PAE, as it is also noted that there is a weak correlation between prostate size and LUTS. Furthermore, prostate size may not be related to obstruction severity, so unilateral embolization may achieve enough organ ischemia to allow symptom improvement, even with lower volume reduction. It may be possible that, unlike uterine artery embolization, PAE might be successful only with unilateral embolization.

Conclusion PAE is a safe and minimally invasive outpatient procedure with preliminary and medium-term follow-up suggesting good symptom control without sexual dysfunction in suitable candidates, associated with a reduction in prostate volume in the majority of cases, which makes this a very promising procedure. Besides good short- and medium-term symptom control in the postprocedure follow-up, more studies are needed to assess if the procedure can be a safe alternative in the management of BPH. PAE should be performed in centers with good postprocedural follow-up programs and interventional radiologists should be directly involved in patient evaluation before and after the procedure during the routine clinical observations.

Acknowledgments The authors would like to thank Sandra Carmo for the precious help and support in defining the best tube angulations for DSA and PAE, and Cla´udia, Teresa Calcas, Ila´dia, and Maria Jose´ for their support in many PAE procedures.

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