How effective is prostatic artery embolization at reducing BPH symptoms as compared to transurethral resection of the prostate in men older than 80 years old?

Scenario: Mr. C is a 102 y/o male with PMHx of BPH, GERD and HTN was admitted to a skilled nursing facility after being discharged from the hospital due to symptoms of lower legs edema, fatigue and dyspnea. Pt was discharged with a urine catheter and diagnosed with acute kidney injury due to BPH. Pt was uncomfortable and tried to pull out the catheter several times. After discussing treatment options with the doctor, the daughter refused to submit his father to invasive procedures due to his advanced age.

Purpose: In patients like Mr. C with past medical history of BPH, urinary tract symptoms, and advanced age, which procedure, TURP or PAE, is more effective at treating BPH symptoms.

Appraised: Daniela Arias Rodriguez

Date of completion: 5/13/2020

Question: How effective is prostatic artery embolization at reducing BPH symptoms as compared to transurethral resection of the prostate in men older than 80 years old?

Search Strategy: For this question, I conducted my entire search in Pubmed by using the terms “Embolization or TURP for BPH.” After applying filters, I obtained a total of 2,460 articles from an original pool of 165, 516 articles. The selected articles were specifically comparing TURP and PAE in patients experiencing symptoms of BPH. Two of these articles are randomized control trials and one is an observational cohort. Articles with higher level of evidence and comparing TURP and PAE were very limited or unaccessible. I selected these articles based on abstract availability, matching terms and date of publication. 

Chosen Articles:

 

• Abt, Dominik, et al. “Comparison of Prostatic Artery Embolisation (PAE) versus Transurethral Resection of the Prostate (TURP) for Benign Prostatic Hyperplasia: Randomised, Open Label, Non-Inferiority Trial.” The BMJ, British Medical Journal Publishing Group, 19 June 2018, www.bmj.com/content/361/bmj.k2338.

• Gao, Yuan-An, et al. “Benign Prostatic Hyperplasia: Prostatic Arterial Embolization versus Transurethral Resection of the Prostate—A Prospective, Randomized, and Controlled Clinical Trial.” Radiology, vol. 270, no. 3, 2014, pp. 920–928., doi:10.1148/radiol.13122803.

• Ray, Alistair F., 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).” Wiley Online Library, John Wiley & Sons, Ltd, 6 May 2018, onlinelibrary.wiley.com/doi/full/10.1111/bju.14249.

 

Evidence Retrieved

1. Abt, Dominik et al, 2018

Level of evidence: Randomized control trial.

Sample/settings: 

• sample size of 103 patients who were treated with PAE or TURP for lower urinary tract symptoms due to BPH. Patients were randomized from February 2014 to May 2017. Forty-eight patients were treated with PAE and fifty-one with TURP. 
• Inclusion criteria was comprised of TURP indication, being 40 y/o or older, failure of previous medical treatment, prostate size of 25-80 ml, an International prostate symptom score (IPSS) of least 8, a maximal urinary flow <12 ml or urinary retention and provided written informed consent.
•  Exclusion criteria was based on existing atherosclerosis disease, noncontractile detrusor muscle, aneurysm changes or tortuosity of aortic bifurcation or iliac arteries, neurogenic dysfunction of the lower urinary tract, urethral stenosis, bladder diverticulum, bladder stone, allergy to contrast, MRI contraindication and  renal failure. 
• Primary outcomes included improvement of IPSS ranging from 0-35; mild symptoms<7, moderate 8-19 and severe symptoms > 20. PAE was performed by an experienced interventional radiologist and the monopolar TURP was carried out by an experienced physician. Data was collected before intervention and at weeks number one, six and twelve after intervention. 

Key findings: 

• From baseline to 12 weeks, the mean IPSS change was -9.23 after PAE and -10.77 after TURP with difference of 1.54 that was not significant (P= 0.31)
• Procedure time was shorter for TURP; however, PAE had better outcomes in terms of blood loss, hospital stay and duration with indwelling catheter.
• After 12 weeks, functional outcomes were markedly superior with TURP. Rate of free urinary flow improved by 5.19 ml/s and 15.34 ml/s after PAE and TURP, respectively (95% confidence interval -14.67 to -5.63; P= <0.001). Moreover, the change in postvoid residual urine improved by -86.36 ml after PAE and -199.98 ml after TURP, (39.25 to 187.98; P= 0.003).
• Fewer side effects were seen with PAE as compared with TURP (16.7% to 45.1%; 0.18 to 0.76; P= 0.005)
• Pain after treatment was reported more with PAE as compared to TURP (56.3% to 31.9%; 1.08 to 2.87; P=0.05)
• IPSS quality of life had an improvement of -2.33 and -2.69 after PAE and TURP, respectively (difference of 0.35, 95% confidence interval -0.30 to 1.00; P: 0.15).
• The chronic prostatitis symptoms index and international index erectile function improved in favour of PAE, although with non-significant p-values of P=0.66 and P=0.53, respectively.
• In terms of bladder outlet obstruction, 93% and 56% of the patients after TURP and PAE, respectively, changed to a less obstructive category. 

Limitations/ Biases: This study had a small sample size and therefore not large enough to definitely establish the inferiority or superiority of PAE over TURP. In addition, it was difficult to establish non-inferiority of PAE due to variability in the IPSS differences among the groups mainly due to difference in the inclusion criteria. Moreover due to the nature of the procedures, the participants and the interventional staff were not blinded leading to possible biases during the collection and interpretation of data. Moreover, PAE was performed either bilaterally or unilaterally in some patients. This inconsistency in the PAE group could have affected as well the patients’ results.  

2. Gao Ya et al, 2014

Level of evidence: Randomized non-blinded control trial

Sample/Settings: 

• Sample size of 114 patients suffering from BPH were randomized into TURP or PAE group. Patients were equally distributed into two groups of 57 participants. 
• Inclusion criteria consisted of an IPSS >7 after failure of medical treatment, prostate volume of 20-100ml, peak urinary flow <15ml/sec and provided written consent.
• Exclusion criteria included hyperactivity/or hypocontractility of detrusor, urethral stricture, prostate cancer, diabetes mellitus, and previous prostate, bladder neck or urethral surgery. 
• Outcomes measured include safety and adverse effects before, during and after surgery as well as complications which were graded I-II as minor and III-IV as major. Other parameters measured include quality of life (0-6, 6 considered as terrible), IPSS (range of 0-35, 35 considered as worst), peak urinary flow, post void residual volume, prostate volume and PSA levels. These parameters were assessed at 1, 3,6, 12 and 24 months. Patients were followed-up for at least 24 months with a mean follow-up of 22.5 months.
• PAE was performed unilaterally in six patients and bilaterally in 48 patients. The PAE group was performed successfully in 54 patients and in 53 patients in the TURP groups. Bipolar TURP was carried out by two experienced urologists under epidural anesthesia followed by saline irrigation with three-way foley catheter. PAE was performed by two interventional radiologists under local anesthesia. Embolization was either unilateral or bilateral depending on prostate arteries accessibility. 

Key Findings: 

• At 12 and 24 months follow-up, both groups showed similar improvements in IPSS, quality of life, peak urinary flow and postvoid residual volume as compared before surgery (P=0.001). Superior improvements in these parameters were noticed with TURP at 1 and 3 months follow-up. 
• Both procedures reduced PSA level and prostate volume as compared to before surgery (P=0.001); however, TURP provided the greatest reduction of PSA and prostate volume. 
• The mean procedure time was shorter with TURP as compared to PAE. Although, less patients required urethral catheter after PAE than with TURP (P=0.001)
• Hospital stay was longer and admissions were higher in the TURP group than PAE group.
• More complications were noticed in the PAE group as compared to the TURP group. In the PAE group, 22 out of 54 patients reported minor complications such as postembolization syndrome and acute urinary retention. Moreover, 8 patients had major adverse events, technical and treatment failures. 
• In the TURP group, 13 out 53 patients reported minor complications such as blood transfusion, acute urinary retention, hematuria, and UTI. In this group, 4 patients had major adverse events such as transurethral resection syndrome, clinical failure and bladder neck stenosis. 
• As compared to PAE, TURP greatly reduced sodium and hemoglobin levels.

Limitations / Biases: This study had a small sample size of 114 patients. The interventional radiologists had variable degree of experience to which researchers attributed the treatment failure rate and the cases of postembolization syndrome in the study. Moreover, patients and researchers were not blind, which could have introduced biases in the results. Some patients underwent unilateral or bilateral PAE based prostate artery accessibility. This could have caused better outcomes in some patients versus those who underwent unilateral PAE.

3. Ray F et al, 2018 

Level of evidence: observational cohort study 

Sample/setting: 

• Setting: performed across 17 urological/interventional radiology centers from July 2014 to January 2014. These centers committed to enter patient’s data into the UK-ROPE system including TURP cases. I
• Sample size 305 patients of which 216 and 89 were submitted to PAE and TURP, respectively. 
• Inclusion criteria: Patients qualified for the study if they had reading/writing abilities and presented with lower urinary tract symptoms, underwent PAE, TURP, HoLEP or open prostatectomy; however, only PAE and TURP cases were included in this study. 
• Outcomes: primary outcome was improvement of IPSS in the PAE group at 12 months. Patients were followed-up at 1, 3, 6 and 12 months via mailed questionnaires. At 3 and 12 months, patients were followed-up at site visit for prostate volume and urine flow assessment. Urine flow and prostate volume were only assessed in the PAE group. 

Key Findings: 

• PAE had a mean duration period of 144 min. Duration of procedure was not collected for TURP.
• PAE improved IPSS and IPSS quality of life by 10 and 2.6 points, respectively. However, greater improvements were seen with TURP with 15 and 3.4 points, respectively. 
• Measurements of prostate volume were not obtained in the TURP group.
• Total reoperation rate after PAE was 43 or 19.9%. 
• Hospital stay was significantly longer for the TURP group as compared to the PAE group (P=0.000)
• Common reported complications included hematuria and hematospermia. Higher cases of hematuria were seen in the TURP group (63.9%) as compared to the PAE group (18.6%). Moreover, more cases of retrograde ejaculation were reported in the TURP group (47.5%) as compared to the PAE group (24.1%). 
• In both groups, the majority of patients reported very low pain after procedures. 
• Patients in the PAE group reported faster median return to normal activities (5 days) as compared to TURP groups (14 days) P= 0.000. 

Limitations/ BiasesThis study is an observational cohort study, which has a lower level of evidence. In this study, the numbers of patients treated with PAE (216 patients) and TURP (89 patients) were not equally distributed, which could have distorted the study’s results. In the TURP groups, 45 patients received monopolar TURP and 44 patients bipolar TURP. There was no clear explanation of these two types of TURP and how these could affect patient’s outcomes. In this study the clinical team used their clinical judgement to determine whether or not the patient was suitable for PAE which can add confounding variables to the study. Researchers acknowledged difficulty recruiting patients for the TURP procedure as well as low response rate to mailed questionnaires. The study also acknowledged receiving research grants from Cook Medical toward the PAE cases indicating a possible conflict of interest. As per the nature of the interventions, researchers and patients were not blinded which could have introduced biases in the study’s results. 

Conclusion(s) 

Abit, Dominik et al, 2018: This study concluded that PAE can be used as an alternative to TURP in treatment of symptomatic BPH. It was found that both treatments provided similar improvement of lower urinary tract symptoms caused by BPH; however, PAE showed smaller improvements. TURP had a shorter procedure time, but PAE had a lesser degree of blood loss, shorter hospital overnight and length of time with bladder catheter. TURP was superior to PAE at improving urine flow, reducing PSA and prostate volume, decreasing post-void residue and urinary frequency. Greater decrease in nocturia and increase in voided volume were observed in the PAE group. Fewer and less severe adverse effects were observed with PAE as compared to TURP. 

Gao Ya et al, 2014: This study concluded that PAE is effective at treating lower urinary symptoms caused by BPH. Because of its technique, it can be an option for non-surgical candidates at high risk for complications. PAE had shorter hospital stay, faster recovery time and had less risk of bleeding, urethral stricture and bladder neck stenosis. Both procedures showed similar improvement in IPSS, quality of life, peak urinary flow, postvoid residual volumes at 12 and 24 months follow-up; however significant improvement was seen with the TURP group at 1 and 3 months as compared to PAE. Moreover, decrease in PSA levels was more pronounced in the TURP group. TURP was performed in a shorter amount of time, but bleeding was noticed as a major complication as well as longer hospital stay and higher rate of admissions. 

Ray F et al, 2018: This study found no evidence that PAE is non-inferior to TURP. Patients treated with PAE improved 10 and 2.6 points in their IPSS and IPSS Qol measurement, respectively. However, TURP was superior to PAE at improving these parameters. However, PAE was found effective and safe at treating lower urinary tract symptoms caused by BPH. It was found that TURP had better improvements than PAE in IPSS measurement and quality of life. Hospital overnight was significantly longer with TURP than with PAE. In terms of complications, hematuria and hematospermia were the most common complications of which hematospermia was higher in the PAE group. Overall less complications were observed with PAE. 

All three studies agreed that TURP was more effective than PAE at treating lower urinary symptoms due to BPH. Prostatic artery embolization is also effective, but not superior to TURP. Transurethral resection of the prostate had greater improvement at increasing urine flow, reducing PSA levels, decreasing prostate and post-void residual volume and urinary frequency. Although, several advantages were found with PAE such as fewer/less severe adverse effects and shorter hospital stay. In advance patients (>80 years old), benefits and complications of both procedures must be discussed with the patients. Considering the safer profile of PAE, it can be offered as an alternative to TURP in patients with advanced age who have high comorbidities, are non-surgical candidates or immunosuppressed patients with high risk of acquiring hospital infections. 

Clinical Bottom Line:

Weight of the evidence 

I weighed the articles in the following order Abt Dominik> Gao Ya > Ray F

Abt Dominick carries the heaviest evidence of my conclusion for being a randomized control trial recently published in 2018. Abt Dominik had a reasonable sample size of 103 patients who were randomized from February 2014 to May 2017. This study directly compared the two procedures of interest and the target population. In this study, both groups were fairly distributed. 

Gao Ya et al is also a randomized control trial with a reasonable sample size of 114 patients. Although this study had a few more patients than Abt Dominik, it was published in 2014. This study also compared the two procedures of interest, TURP and PAE, as well as the target population. In this study, patients were equally distributed into two groups of 57 participants. 

Ray F et al  is an observational study performed across 17 urological/interventional radiology centers from July 2014 to January 2014. This study had a sample size of 305 patients, which is a better sample size than the two previous studies; however, it had a lower level of evidence.   In this study, patients were unequally assigned to the groups (PAE 216 patients and TURP 89 patients). Researchers acknowledged difficulty recruiting patients for the TURP procedure. In addition, the data collected was very subjective. Two types of TURP were utilized and their effects on patients’ outcome were not explained. Adding to this, researchers acknowledged a possible conflict interest.

Magnitude of any effects

Abit, Dominik:  PAE was found to be an alternative to TURP due to similar effects at improving IPSS. Among these two groups, a non-significant IPSS difference of 1.54 (P=0.31) was found. Moreover, after 12 weeks, TURP was superior at improving urinary flow (P= <0.001), postvoid residual volume (P= 0.003) and bladder obstruction in 93% of patients making it more appropriate for patients with severe symptoms of BPH such as bladder outlet obstruction, acute urinary retention and other complications.

Gao Ya et al: Greater improvements were noticed in IPSS, quality of life, urinary flow and postvoid residual volume with TURp at 1 and 3 months mainly due to its immediate ablation effects as compared with PAE whose effects on the prostate can take several months. Both procedures improved these parameters at 12 and 24 months (P=0.001).

Ray F et al: No evidence were found that PAE is non-inferior to TURP. PAE improved IPSS and IPSS quality of life by 10 and 2.6 points, respectively. TURP improvements improved IPSS and IPSS quality of life by 15 and 3.4 points, respectively. This indicates that PAE has certainly similar effects as TURP at improving BPH symptoms.

Clinical significance Among these two procedures, the evidence shows that TURP has certainly better outcomes at almost all the parameters such as improving urine flow, reducing PSA levels, decreasing prostate and post-void residual volume, urinary frequency and quality of life. Moreover, TURP seems to have more immediate effects than PAE. In PAE, the prostate blood supply is obstructed, so that the gland shrinks over time alleviating symptoms of BPH. Both of these procedures have involved complications and adverse effects with TURP having more serious complications than PAE such as bleeding. In patients older than 80 year old whose symptoms are limiting their daily activities, want to keep themselves active and desire a definitive treatment, TURP might be a good option based on its good profile at improving BPH symptoms and providing more immediate relief. In patients like Mr. C who is 102 years old and whose life-expectancy is not high, providing none of these interventions might be a more appropriate approach. As mentioned previously, TURP has better outcomes, but more serious complications. In addition, the effects of PAE on the prostate size take longer than TURP and reoperation is more likely.

Any other considerations important in weighing this evidence to guide practice Larger scale randomized control trials with greater numbers of participants addressing this topic are certainly needed. Moreover, PAE and TURP techniques should be improved, so that patients receive a more uniform treatment in each group. In both RCTs, some patients received unilateral or bilateral PAE or monopolar or bipolar TURP. Trials with longer follow-up are needed to assess the long term effectiveness of PAE.