Urodynamic Effects of Prostatic Urethral Lift Procedure for Male Voiding Lower Urinary Tract Symptoms

Abstract

Aims:

Primary objective is to investigate whether prostatic urethral lift (PUL) results in an improvement of urodynamic parameters that define bladder outlet obstruction (urethral resistance algorithm [urethral resistance factor (URA)], Schäfer grade, detrusor pressure at maximum flow [P_det Q _max], and detrusor pressure at bladder opening [P_detOpen]).

Materials and Methods:

Twenty patients (main inclusion criteria: ≥50 years of age, benign prostatic obstruction (BPO), international prostate symptom score (IPSS) ≥13, prostate volume ≤60 mL, and no middle prostate lobe) were enrolled in the study and a PUL was performed. Patients underwent urodynamic investigation and filled out the IPSS and quality of life (QoL) before and after PUL. A paired t-test was used to analyze the results.

Results:

The mean age was 68 years (range 55–79), mean prostate volume (TRUS) was 45 mL (range 20–59), and mean prostate-specific antigen was 2.0 μg/L (0.2–4.4). IPSS of the 16 patients reduced significantly (from 22.20 to 14.47, p = 0.000). Q _max during pressure flow study improved significantly (from 4.5 to 7.2 mL/s, p = 0.001), no significant difference was found in Q _max during free uroflowmetry. There was no significant difference found in postvoiding residual. URA decreased significantly post-treatment (from 52 to 37 cmH₂O, p = 0.000). The Schäfer obstruction plot decreased significantly (from 3.5 to 2.6, p = 0.022). Seven patients underwent Greenlight Laser Vaporization of the prostate after the PUL attributable to unsatisfactory results.

Conclusions:

PUL has desobstructive effects, but they seem clinically modest. The procedure improves urodynamic parameters as well as QoL in males with lower urinary tract symptoms based on BPO. However, the mechanism how PUL leads to a remarkable symptom relief remains unclear and cannot be explained by the desobstructive mechanisms we observed.

Introduction

Benign prostatic hyperplasia (BPH) can cause bothersome lower urinary tract symptoms (LUTS), which can detrimentally affect a man's quality of life (QoL).¹ Moderate to severe LUTS is estimated to affect 30% of men >50 years of age or about 26 million men in Europe.² Men suffering from LUTS caused by BPH typically experience frequent and urgent need to urinate both during the day and night and often experience interrupted sleep. The treatment options for a patient presenting with bothersome LUTS range from watchful waiting to pharmacological therapy to (surgical) interventional procedures. Treatment of BPH is about improving a man's QoL with respect to all aspects. For example, if a man achieves relief from his LUTS and yet loses the ability to perform sexually or maintain continence, his QoL might still decline. The measure of BPH therapy effectiveness should therefore be comprehensive: it should reflect the nature of the disease and the desires of the patients who seek care.

Earlier studies have shown a good symptomatic response of the prostatic urethral lift (PUL) system in patients with LUTS.^3,4 Although symptomatic improvement may be the most important parameter from a patient's point of view, objective measurable parameters of improvement are also relevant for urologists to understand the working mechanism of the applied technique and to monitor the degree of desobstruction and duration of effectiveness. However, the latter is not well studied for PUL. For established ablative therapies such as transurethral resection of the prostate (TURP), it is well known that a radical desobstruction almost always leads to a very high symptom reduction. The PUL procedure is a minimally invasive treatment for voiding LUTS secondary to BPH. It has met all the applicable performance standards established by the medical device directive for the treatment of symptoms because of urinary outflow obstruction secondary to BPH in men older than 50 years. With the use of this PUL procedure, the symptomatic improvement of LUTS is in the range of the TURP, whereas flowmetry parameters improve only moderately.^4,5 This discrepancy is poorly understood, because the PUL system claims to be designed to relieve obstruction.⁶ The purpose of this study is to measure changes in urodynamic parameters, including obstruction parameters during pressure flow studies before and after the PUL procedure. We try to identify which of these parameters may be responsible for the symptomatic response. We hypothesize that symptomatic improvement is associated with a decrease in bladder outlet obstruction.

Study objectives

Primary objective

To investigate whether PUL therapy results in the improvement of urodynamic parameters that define bladder outlet obstruction (urethral resistance factor [URA], detrusor pressure at maximum flow [P_det Q _max], and detrusor pressure at bladder opening [P_detOpen]).

Secondary objective

To investigate whether there is a correlation between the change in urodynamic obstruction parameters and symptomatic response after performing PUL therapy.

Materials and Methods

Ethical approval for this study was obtained from the Radboudumc's ethical review board. Patients who met the inclusion criteria with the diagnosis of benign prostatic obstruction (BPO) were asked to participate in this study. Inclusion criteria were as follows: male gender ≥50 years of age, prostate volume ≤60 cc measured on transrectal prostate ultrasnography, international prostate symptom score (IPSS) ≥13, and URA of ≥29 at pressure flow plot. Exclusion criteria were as follows: among others, median lobe or intravesical protrusion of the prostate. The full list of exclusion criteria is listed in Table 1.

Table 1.

Exclusion Criteria

Active urinary tract infection or bacterial prostatitis at the time of treatment

Cystolithiasis within 3 months of the procedure

Obstructive median lobe

Intravesical prostatic protrusion >5 mm (identified with TRUS or cystoscopy)

Current urinary retention

Urethral conditions that may prevent insertion of a 20 French rigid cystoscope

Previous TURP or laser procedure

Pelvic surgery or irradiation

PSA above reference level, unless prostate carcinoma is ruled out

Severe cardiac comorbidities

Other medical condition or comorbidity contraindicative for TURP or PUL

Neurogenic LUTS patients

Dysfunctional voiding

Hypocontractile bladder (when BCI: P_det Q _max + 5Q _max <100)

Alpha blocker usage within 2 weeks or 5-Ari usage within 3 months of baseline assessments and treatment

BCI = bladder contractility index; LUTS = lower urinary tract symptoms; P_det Q _max = detrusor pressure at maximum flow; PSA = prostate-specific antigen; PUL = prostatic urethral lift; TRUS = transrectal ultrasound; TURP = transurethral resection of the prostate.

All patients underwent the preprocedure diagnostic workup at baseline in the form of IPSS questionnaires, flowmetry and postvoid residual (PVR) measurement, transrectal ultrasonography of the prostate, urethrocystoscopy, pressure flow studies, prostate-specific antigen (PSA), and urine culture (Table 2).

Table 2.

Diagnostic Workup

Diagnostic test	Time to PUL procedure
IPSS and QoL questionnaire	Within 30 days before PUL and after med wash-out
Flowmetry and PVR	Within 30 days before PUL and after med wash-out
TRUS	Within 6 months before PUL procedure
Urethrocystoscopy	Within 6 months before PUL procedure
Urodynamics/pressure flow studies	Within 30 days before PUL and after med wash-out
PSA	Within 6 months before PUL procedure
Urine culture	Within 30 days before PUL

IPSS = international prostate symptom score; PVR = postvoid residual; QoL = quality of life.

After the diagnostic workup, the PUL procedure was performed under general anesthesia in all patients. Patients were admitted on the day of the procedure and generally discharged the day after the procedure. Time from OR to discharge was recorded and the required catheterization time in each patient was recorded. Follow-up visits were performed at 6 weeks and at 3 months. The following evaluations were performed during these visits:

Six weeks post-treatment: IPSS and ICIQ QoL, uroflowmetry (Q _max, voided volume [V _voided], and PVR), and history of urinary catheterization: duration of catheterization (days).

Three months post-treatment: IPSS and ICIQ QoL, history of urinary catheterization, and pressure flow studies with digital waveform recording (uroflowmetry, URA, BOOI, opening pressure, P_det at Q _max, and detrusor overactivity [yes/no]).

Statistical analysis

A paired t-test was used to analyze the results; a p-value ≤0.05 was considered significant. The data were analyzed using SPSS (V25, IBM, Armonk, NY).

Results

Twenty patients were enrolled in the study. The PUL procedures were carried out between October 2016 and November 2018. The average number of implanted anchors was 4.52 per patient (range 3–7). Patient characteristics are shown in Table 3.

Table 3.

Patient Characteristics

Patient characteristic	Average (spread)
Age (year)	68 (55–79)
Prostate volume (mL)	44.7 (20–59)
PSA (ng/mL)	2.07 (0.26–4.40)
Q _max pretreatment (mL/s)	8.25 (5–13)
PVR pretreatment (mL)	117 (0–325)
IPSS pretreatment	22 (12–28)

None of these 20 patients reported symptoms of incontinence of retrograde ejaculation. The results are summarized in T able 4.

Four urodynamic studies were discarded. In two patients because the patients were not able to void (pretreatment), and in two patients because the abdominal catheter was displaced during the micturition phase (post-treatment). Final analysis was performed on 16 patients.

IPSS was reduced significantly after 3 months (from 22.20 to 14.47, p = 0.000). Also, the IPSS QoL improved significantly after treatment (from 3.73 to 2.47, p = 0.005). Q _max during pressure flow study improved significantly (from 4.5 to 7.2 mL/s, p = 0.001), whereas there was no significant difference found in Q _max during free flow (6.9 pretreatment to 8.3 mL/s post-treatment). If corrected for volume voided >150 mL (n = 6 both pretreatment and post-treatment), there was also no significance in free Q _max pretreatment and post-treatment (9.2 pretreatment to 11.7 mL/s post-treatment). There was no significant difference found in postvoiding residual volume before and after treatment (114 mL before and 136 mL after). Although opening pressure of the bladder decreased after operation (from 71 to 61 cmH₂O), this difference was not significant. Also, closure pressure of the bladder remained unchanged after operation. URA decreased significantly post-treatment (from 52 to 37 cmH₂O, p = 0.000). Also, the Schäfer obstruction plot decreased significantly (from 3.5 to 2.6, p = 0.022). If we consider a URA of <29 cm H₂O as nonobstructive, 13 patients had an obstructive URA pretreatment (we observed 3 missing values) and 10 patients still had an obstructive URA post-treatment (1 missing value). When we consider Schäfer obstruction plot ≥ III obstructive, 11 patients had obstructive Schäfer plots pretreatment (1 missing value) and 7 patients had obstructive Schäfer plots post-treatment (0 missing values). At 1 year of follow-up, 8 patients were satisfied with the results of the PUL. Six patients still needed to use medication owing to insufficient satisfaction with the PUL (three patients used silodosin, one used alfuzosin, one used alfuzosin in combination with finasteride, and one used dutasteride). One patient started self-catheterization because of high residuals after voiding. Eventually, seven patients underwent a Greenlight Laser Vaporization because of unsatisfactory results. This procedure was carried out 7–40 months after PUL.

Interpretation of results

PUL decreases LUTS subjectively based on improvement of IPSS, including the QoL question, which has been shown previously. The mean improvement is from the moderate/severe range (IPSS 22) to the moderate range (IPSS 14). This study furthermore analyzed the urodynamic pressure flow results. When interpreting the obstruction plots URA and the Schäfer classification, the desobstructive effects of PUL are modest at best. Analyzing URA, 10/13 (76%) were still obstructed after PUL treatment. With the Schäfer classification, 7 out of 11 (64%) of patients were still obstructed after treatment.

Discussion

The PUL is a minimal invasive endoscopic technique for treatment of LUTS in males with BPO. Literature already showed that this technique provides a comparable decrease of LUTS as after TURP, whereas uroflowmetry just shows an improvement in flow comparable to an alpha blocker.^4,7 This study assesses objective urodynamic effects with pressure-flow curves. The primary objective of our study was to investigate whether PUL results in an improvement of urodynamic parameters that define bladder outlet obstruction (urethral resistance algorithm [URA], Schäfer grade, P_det Q _max, and P_detOpen).

Some of the results of our study are concordant with earlier research.⁷ Although there is a clear reduction in symptoms and an improvement in QoL, Q _max improvement is not significantly different pretreatment and post-treatment. URA decreased significantly from 52 cmH₂O to a level of 37 cmH₂O. However, internationally, a URA >29 cmH₂O is still considered to be an obstructed flow. This indicates that the PUL has some desobstructive capacity, however, modest at maximum. We hypothesize that the mechanism behind this is that some urodynamic parameters might improve slightly (P_det Closure and P_det Opening) and some improve significantly (Schäfer Obs, and URA). This can lead to a symptomatic relief, whereas the objective results can still be too marginal to measure. A subanalysis of each separate question of the IPSS (Table 5) was done to assess whether it was the voiding symptoms that improved or the storage symptoms. However, both voiding as well as storage symptoms improved significantly. The only factor that did not improve is the frequency of nocturia, which is the only objective (measurable) variable in the IPSS questionnaire. It appears that the experienced relief of symptoms is significant, whereas there is only a slight improvement in objective values such as flow and nocturia, which is in the range of pharmacological treatment of LUTS with alpha blockers or five alpha reductase inhibitors. An explanation for this may be that alterations to the bladder neck can cause alteration in the neurological “pacemaker system” of the bladder. De Jongh et al. described in 2007 in a study in guinea pigs how alterations to the bladder neck, not obstruction per se, can result in altered non micturition activity, which contributes to increased afferent output. In turn, this contributes to the increased sensations of urge associated with bladder dysfunction.⁸ One hypothesis can be that by release of tension on the bladder neck, sensations of urge can decrease.

Table 4.

results

Variables n = 16	n	Mean pre-PL procedure (SD)	Mean 3 m after PL procedure (SD)	p-value
IPSS total score	20	22.20 (4.95)	14.47 (8.07)	0.000^*
IPSS QoL	20	3.73 (0.59)	2.47 (1.41)	0.005^*
Q _max at free flow	16	6.9 mL/s (3.4)	8.3 mL/s (4.7)	0.229
Q _max at free flow, voided volume >150 mL	6	9.2 mL/s (4.1)	11.7 mL/s (5.3)	0.968
Cystometric capacity (mL)	16	365.33 (141.18)	359.07 (133.09)	0.847
Q _max at pressure flow	16	4.5 mL/s (2.2)	7.2 mL/s (3.3)	0.001^*
Residual urine	16	114 mL (100)	136 mL (118)	0.377
UDO P_det Q _max (cmH₂O)	16	62.93 (17.40)	56.27 (21.94)	0.114
P_detOpen	16	71 cmH₂O (36.7)	61 cmH₂O (24.2)	0.08
P_detClosure	16	45 cmH₂O (20.1)	40 cmH₂O (7.0)	0.36
URA	13	52 cmH₂O (17.1)	37 cmH₂O (14.9)	0.000^*
Schäfer	15	3.5 (1.3)	2.6 (1.3)	0.022^*
UDO Schäfer CON plot		2.20 (0.86)	2.13 (0.83)	0.827
UDO Wattsfactor Max		12.34 (5.71)	13.33 (8.82)	0.732
UDO Wattsfactor Q _max		9.44 (3.04)	10.39 (6.57)	0.686

Significant.

P_detOpen = detrusor pressure at bladder opening; PL; SD = standard deviation; URA = urethral resistance factor.

Table 5.

international Prostate Symptom Score Subscore Results

Pair	Individual value	Mean	SD	p
Pair 1Incomplete emptying	IPSS Q1 pre	3.5	1.41	0.000^*
Pair 1Incomplete emptying	IPSS Q1 at 3 m	1.9	1.36	0.000^*
Pair 2Frequency	IPSS Q2 pre	3.5	1.06	0.030^*
Pair 2Frequency	IPSS Q2 at 3 m	2.5	1.36	0.030^*
Pair 3Intermittency	IPSS Q3 pre	3.4	1.50	0.004^*
Pair 3Intermittency	IPSS Q3 at 3 m	2.0	1.60	0.004^*
Pair 4Urgency	IPSS Q4 pre	2.6	1.05	0.036^*
Pair 4Urgency	IPSS Q4 at 3 m	1.9	1.36	0.036^*
Pair 5Weak stream	IPSS Q5 pre	4.5	0.64	0.000^*
Pair 5Weak stream	IPSS Q5 at 3 m	2.5	1.55	0.000^*
Pair 6Straining	IPSS Q6 pre	2.5	1.60	0.013^*
Pair 6Straining	IPSS Q6 at 3 m	1.6	1.40	0.013^*
Pair 7Nocturia	IPSS Q7 pre	2.3	1.18	0.262
Pair 7Nocturia	IPSS Q7 at 3 m	2.0	1.39	0.262
Pair 8Combined score	IPSS Total pre	22.3	4.95	0.000^*
Pair 8Combined score	IPSS Total at 3 m	14.5	8.07	0.000^*

We notified a significant improvement in Q _max when it was measured during a pressure flow study. However, the improvement in free Q _max is not statistically significant. A reason for this might be that during a pressure flow study, the bladder is always filled to a maximum capacity during voiding, whereas during a free Q _max, bladder filling may vary among patients. We tried to correct this by performing a subanalysis of free uroflow in patients who had more than 150 mL V _voided at free flow. Free flow improvement is not significant in this very small subgroup. The observation that the values of Q _max are all lower during a pressure flow study is explained by the presence of a measurement catheter in the urethra, occupying part of the lumen and thereby reducing flow.

In published literature, often, PUL is being compared with more invasive procedure technologies like TURP or green light laser.⁷ It can be well reasoned that the results in terms of uroflow are better in the invasive surgery group, since tissue is removed, opening the prostatic urethra, whereas in PUL, tissue is only retracted. Patients who desire the best desobstructive therapy should undergo an invasive treatment. However, these results come at the cost of surgery under general/spinal anesthesia, retrograde ejaculation, and a small chance of incontinence or erectile dysfunction. The procedure can be used as a method to delay chronic pharmacological treatment or invasive surgery. In the BPH 6 study, PUL was compared to TURP. TURP has proven to be superior in IPSS score reduction, Q _max improvement, and PVR reduction. PUL has proven to be superior in the preservation of antegrade ejaculation.⁴

Our opinion is that PUL should be considered in a select group (of relatively young) of patients who do not want to have an invasive treatment and do not want the side effects of pharmacological treatment.⁹ We would argue to reserve the PUL treatment for a select group of patients with a desire to preserve antegrade ejaculation and avoid the risk of complications such as incontinence or erectile dysfunction. Also, patients who want to refrain from medication and at the same time do not want to undergo general/spinal anesthesia are good candidates. The PUL treatment can ultimately be performed in an outpatient clinic setting with the use of topical anesthesia and treatment will take ∼30 minutes. Post-treatment catheterization is not necessary. When patients are not satisfied with the results, a more invasive treatment can be performed. In the seven patients in our study, who were not satisfied with the results of PUL, we could perform green light laser of the prostate with satisfactory results and without complications.

Limitations

Our study population was small since it is only an exploratory study. In 4 patients, the pressure flow study was not of sufficient quality to analyze, leading to 16 usable pressure flow studies. In our patient population 7 out of 20 (35%) underwent a green light laser after PUL treatment of the prostate because of unsatisfying results. This number is higher than reported in literature (9.3%).¹⁰ An explanation for this is not straightforward. It could be the relatively limited experience of our surgeon with the PUL system, although he performed over 20 procedures at forehand. Since our inclusion criteria are concordant with literature (prostate size, no middle lobe, etc.), selection bias does not appear to be the cause of this high re-treatment rate. We compared our patient characteristics to those in the L.I.F.T. study and they were remarkably similar: age 68 years in our study vs 67 years in the L.I.F.T study, prostate volume 44.7 vs 44.5 mL, PSA 2.07 vs 2.4 ng/mL, PVR pretreatment of 117 vs 85.5 mL, and Q _max pretreatment 8.25 vs 8.9 mL/s in our study vs LIFT study, respectively.¹⁰ There was no adverse effect from the presence of PUL implants during and after green light laser treatment of these patients, which is concordant with literature.¹⁰ Therefore, we can conclude that green light laser therapy of the prostate is a valid salvage therapy when PUL does not suffice. In our center, the average number of implantation devices is 4.52 (range 3–7). A meta-analysis by Tanneru from March this year describes 5 studies with an average implant use ranging from 3.8 in one study to 5.2 in another.⁷

Conclusion

PUL has desobstructive effects, but they seem clinically modest. The procedure improves urodynamic parameters as well as QoL in males with LUTS based on BPO. However, the mechanism of how PUL leads to a remarkable symptom relief remains unclear and cannot be explained by the desobstructive characteristics we observed. In our population, PUL was successful in about one-third of the selected patients. About one-third still needed to use medication after the procedure. Seven patients (about one-third) eventually underwent Green Light Laser desobstruction of the prostate.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

An unrestricted research grant was provided by NeoTract, Inc.

Abbreviations Used

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