Outcomes of prostatic urethral lift in a medically complex population at a veterans affairs hospital

Abstract Objective The objective of this study is to report “real‐world” outcomes of prostatic urethral lift (PUL) in a medically complex US military veteran population while employing liberalized procedural indications. Methods A retrospective review was conducted of patients who underwent PUL at our institution. There were no prostatic size requirements, patients were accepted on anti‐platelet/anticoagulant therapy, no benign prostatic hyperplasia (BPH) medication washout was required, and there was no maximum post‐void residual PVR. Pre‐ and post‐operative International Prostate Symptom Score (IPSS), uroflowmetry, and PVR were recorded. Statistical comparisons were performed using simple t tests. Results From 2013 to 2019, 91 patients underwent PUL. Mean age was 70 (range 55–92) years. The majority of our patients were classified as American Society of Anesthesiologists (ASA) class 3 versus the general population at ASA class 2. Post‐operatively, IPSS decreased by an average of 43% (23 to 13, p < 0.001). There was a mean 41% decrease in PVR (179 to 101 cc, p = 0.009), which was durable for a follow‐up of up to 54 months. Maximum urinary flow rate improved by an average of 32% (9.3 to 12.3 cc/s, p = 0.003), which was also durable throughout follow‐ up. Forty‐four patients required catheterization pre‐operatively and 16 required catheterization post‐operatively. Therefore, 27 patients (61.4%) were rendered catheter‐free by PUL. Thirty‐nine patients were taking antiplatelet medications peri‐operatively, and 13 took anticoagulants. Only one patient (on warfarin) experienced hematuria requiring re‐admission with catheter placement. Conclusions PUL produced effective and durable results in our veteran population, including in patients with significant pre‐operative bladder decompensation and those on antiplatelets/anticoagulants.


| INTRODUCTION
Prostatic urethral lift (PUL) is a minimally invasive intervention for symptomatic benign prostatic hyperplasia (BPH) that has been approved for use in the United States since 2013 for prostate sizes up to 80 g. 1 In PUL, a rigid cystoscope is used to place transprostatic clips onto the anterolateral prostate, compressing prostatic tissue to create an open anterior lumen. 2 For patients who do not receive adequate symptom relief from medical management of BPH or for those who find medication side effects to be intolerable, PUL has emerged as an alternative to prostatic vaporization or traditional transurethral resection of the prostate (TURP). 3 While studies have shown that PUL is effective in improving lower urinary tract symptoms (LUTS), more work is needed to establish the efficacy of PUL in a real-world clinical setting, with liberalized inclusion and exclusion criteria applied. 4,5 In addition, previous work has not reported use of PUL in populations with significant medical comorbidities, which are associated with increased operative risk and higher frequency of adverse outcomes in procedures, even minimally invasive ones. This study examines outcomes of PUL in a medically complex US military veteran population, while employing more liberalized patient selection criteria.

| BACKGROUND
PUL may present several advantages over TURP in reducing side effects from the procedure, while having acceptable improvements in objective voiding measures. PUL has been shown across multiple studies to provide effective relief for LUTS from BPH. 6 While the international prostatic symptom score (IPSS) improves by 3-5 points with medical management, IPSS improves by up to 11 points with PUL, compared to 14 points with TURP. 1 PUL has additionally performed better than TURP using an alternative characterization of BPH symptoms called the BPH6, which includes specific endpoints for LUTS relief, recovery experience, erectile function, ejaculatory function, continence preservation, and safety. In a prospective randomized controlled trial of 80 patients across 10 European centers, PUL was found to have better outcomes in the BPH6 domains than TURP overall, with 52.3% of individuals who underwent PUL meeting BPH6 primary endpoints versus 20.0% of those who underwent TURP (noninferiority p < 0.0001; superiority p = 0.005). 7,8 While TURP carries a small risk of post-operative erectile dysfunction (ED), studies have demonstrated that PUL may actually even improve the Sexual Health Inventory in Men (SHIM) score in men with severe erectile dysfunction (ED). 9 In addition, PUL has also been found to have cost-savings associated with its ability to be performed as an outpatient procedure and its low complication rates. 10,11 Modeling the UK National Institute for Health and Care Excellence showed that when PUL is performed as an outpatient surgery, PUL produced savings of £286 per patient compared to monopolar TURP £159 per patient compared to bipolar TURP and £90 per patient compared to holmium laser enucleation of the prostate (HoLEP). 11 The efficacy of PUL was initially demonstrated in a clinical trial with 5-year follow-up, in the Luminal Improvement Following Prostatic Tissue Approximation (LIFT) study by  This sham-controlled trial with 206 subjects showed IPSS improvement of 41.1% at 3 years and 36% at 5 years. The study group faced fairly rigorous inclusion criteria, including no prior surgical treatment for BPH, 2-week α-blocker washout, 3-month 5α-reductase inhibitor washout, maximum urinary flow rate (Qmax) of 12 ml per second or less, 30 to 80 cc prostate, no median lobe obstruction, and pre-operative postvoid residual (PVR) urine volume less than 250 ml. 14 Despite multiple studies that have proven the broad possible applications of PUL, we aim to enhance the current literature by showing that PUL is likewise effective in patients with significant medical comorbidities (including many on long term anti-platelet or anti-coagulant therapy) and in patients with considerable preoperative bladder deconditioning and urinary retention. The inclusion criteria were men with symptomatic BPH who had failed medical therapy or who desired surgical intervention for their BPH symptoms who were surgical candidates. Our local VA urology practice removed urinary retention requiring catheter drainage as an exclusion criterion for PUL, as a significant number of veterans were referred to urology in retention yet were observed to have robust bladder contractility on pressure-flow studies. These patients often had a high comorbidity index, so we aimed to study if this surgical modality could be used to relieve their outlet obstruction effectively.

| RESULTS
From 2013 to 2019, 91 veteran patients underwent PUL at our institution ( Table 1). Diagnosis of BPH with prostate suitable for PUL included IPSS, uroflowmetry, and PVR, followed by additional assess- Subjectively, IPSS decreased significantly (23 to 13, p < 0.001) by a mean of 10 points, consistent with prior studies. The average SHIM score changed from 8.1 pre-operatively to 9.1 post-operatively, a trend towards improved erectile function that was not statistically significant (p = 0.57). Objectively, there was a significant decrease in post-void residual urine volumes after PUL (179 to 101 cc, p = 0.009), which was found to be durable for a follow-up of up to 54 months (Table 2). In addition, the peak urinary flow rate improved significantly (9.3 to 12.5 cc/s, p = 0.003), which was also found to be durable for a follow-up of up to 54 months.
The surgical failure rate of PUL in our patient population was 11.0%. Two individuals in our study (2.1%) underwent a second PUL procedure, and eight individuals (8.8%) underwent subsequent TURP for persistent bothersome symptoms after initial PUL. There was no significant difference (p > 0.05) in the median age, pre-operative PVR, IPSS, Qmax, or prostate volume between individuals who did and did not require a second prostate procedure. All men on medical therapy were continued on medical therapy post-operatively to provide some benefit in post-operative edema, bleeding, and irritative symptoms.  of patients having a PVR greater than 250 ml, which was less than half of the incidence in our study population. In addition, the average age of patients in the German cohort was 66.2 AE 11.5, while it was 70 AE 8.1 in our study population. These values suggest a significantly higher level of bladder decompensation and retention in the patients we describe, which provides important support that PUL can be effective even in these circumstances.
Eure et al. 17  in urinary retention in their study, out study population included 48% of patients in urinary retention pre-procedurally as compared to 11.7% pre-procedurally in their study. Finally, their study does not report on the prevalence of significant medical comorbidities or ASA score. Despite the differences in patient population, our studies report similar improvements in IPSS and Qmax outcomes. We show a 10-point reduction in IPSS in our study versus an 8.1-point reduction in IPSS in their study. We demonstrate a 3.2 ml/s improvement in Qmax, while they demonstrate a 0.4 ml/s improvement in Qmax. Our study furthers their conclusion that PUL is highly effective in a realworld non-selected patient population by showing that even with high levels of pre-operative retention and significant medical comorbidities, the procedure remains safe, effective, and durable.
We describe the successful implementation of PUL in a highly comorbid population. The average ASA classification among our patient cohort was 3.14. An ASA score of 3 is defined as "patients  3,8,13,19,20 Despite a medically complex patient population, with many on anti-coagulants and other medications, our complication rate fell inside these bounds ( receive a TURP for an overall retreatment rate of 11.0% throughout follow-up of up to 4.5 years. The limitations of our paper include its retrospective nature and the lack of a sham control group to assess comparative outcomes. In addition, our patients did not routinely undergo urodynamic study (UDS) to assess for other etiologies of voiding dysfunction, which may in part explain why 19% still required CIC or indwelling Foley following PUL. Our experience suggests that in patients where bladder decompensation is suspected, clinicians may be advised to routinely perform UDS prior to consideration of procedures to address BPH.
Finally, our paper was limited by the fact that PUL was performed by several different clinicians at the attending and resident level, meaning we were unable to control for specific surgeon technique or level of experience.

| CONCLUSIONS
Our real-world clinical application of the PUL demonstrated that it has effective, safe, and durable results in a medically complex veteran population, including in patients requiring catheterization, patients with significant urinary retention, and those on antiplatelets/anticoagulants. Based on our findings, we conclude that PUL is an appropriate treatment option for symptomatic BPH, even in individuals with severe LUTS and significant medical comorbidities.

CONFLICT OF INTEREST
The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this manuscript.