Rezum Outcomes in Relationship to Number of Injections: Is Less More?

Abstract

Objectives:

To assess efficacy and safety outcomes in relationship to the number of injections given during Rezum treatment.

Methods:

A retrospective study was conducted on patients with moderate to severe lower urinary tract symptoms (LUTS) treated with Rezum. Patients were stratified into cohorts based on the number of injections received per lateral prostatic lobe: 1, 2, 3, or 4 injections. International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), postvoid residual (PVR), International Index of Erectile Function (IIEF)—Erectile Function, IIEF—Orgasmic Function, and adverse events were collected at baseline, 1, 3, 6, and/or 12 months postoperatively.

Results:

A total of 179 patients were included: 58, 91, 22, and 8 patients in the 1, 2, 3, and 4 injections cohorts, respectively. Baseline demographics significantly different across cohorts were age, history of urinary retention, prostate-specific antigen, prostate volume, prostatic urethral length, and presence of median lobe. At 3 months, all cohorts reported significant improvements in IPSS and QoL, which remained durable to 12 months. There were no significant differences in changes in IPSS, QoL, PVR, and IIEF—Erectile and Orgasmic Function between the cohorts at any follow-up. Multiple linear regression showed that the number of injections did not predict changes in IPSS, QoL, PVR, and IIEF—Erectile and Orgasmic Function at any follow-up (p > 0.05) but predicted change in Qmax at 3 months (β = 5.7, p = 0.019). Multiple logistic regression showed that for each additional injection, the odds of gross hematuria, penile burning, penile pain, and dysuria increased by 3.8, 2.6, 2.2, and 3.0, respectively.

Conclusions:

Utilizing less injections represents a safe treatment strategy without compromising Rezum's efficacy in providing durable relief in LUTS.

Introduction

The Rezum System (Rezum; Boston Scientific, Marlborough, MA, USA) is a minimally invasive surgical therapy that uses convective radiofrequency water vapor thermal energy to ablate obstructive prostatic lobes, resulting in cell necrosis and improvement in lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).¹ Water vapor at 103°C is delivered through a retractable needle, which is injected into the lateral and/or median lobes of the prostate.² The needle can be retracted and repositioned along the prostatic urethra for up to 15 treatments per device. Traditional treatment approach determines the number of injections to use per lobe by the prostatic urethral length, with 1–2 injections for <2 cm, 2–3 injections for 2–3 cm, and 3–4 injections for >3 cm.³

Recently, the benefits of Rezum have been demonstrated across various groups of patients, including those with urinary retention, small prostates (<30 cc), large prostates (>80 cc), and obstructive median lobes.^4

–9 However, there is paucity of studies describing the ideal number of injections/treatments needed to achieve symptom improvement while minimizing the occurrence of adverse events (AEs). Determining the ideal number of injections can also provide insights on ways to decrease health care costs associated with surgical or medical retreatment after inadequate or incomplete treatment with Rezum from not using the optimal number of injections. Thus, we assessed the efficacy and safety of Rezum outcomes in relationship to the number of injections given during treatment.

Methods

We conducted a single center, retrospective study on patients from a multiethnic population treated with Rezum by two urologists between December 1, 2017 and April 30, 2019. Patients were included if they had a recorded baseline International Prostate Symptom Score (IPSS) between 8 and 35, prostate volume, maximum urinary flow rate (Qmax), prostate-specific antigen (PSA), and at least one follow-up within 12 months after treatment. Patients were excluded if they had an active urinary tract infection (UTI) within 7 days of the procedure, urinary retention requiring catheterization on the day of the procedure, a prior Rezum procedure, ongoing prostate cancer, or a PSA ≥10 ng/mL unless prostate cancer was ruled out by biopsy. Patients with median lobes were not excluded. Patients were categorized into one of four cohorts based on the number of injections used per lateral prostatic lobe: 1, 2, 3, or 4 injections.

All patients received perioperative antibiotics and elected for either general anesthesia or prostate block before treatment. During treatment, patients received water vapor injections at 103°C for 9 seconds on the prostatic lateral and median lobes (if present). The number of injections used per patient was at the discretion of the urologist, but the majority of patients received 1 injection per cm of prostatic urethral length. All patients were catheterized following treatment.

Outcome measures, including IPSS, quality of life (QoL), Qmax, postvoid residual (PVR), International Index of Erectile Function (IIEF)—Erectile Function, and IIEF—Orgasmic Function, were collected at baseline and 1, 3, 6, and/or 12 months postoperatively. Qmax was collected through uroflowmetry with a minimum voided volume of ≥125 mL. Prostate volumes were measured through a transrectal ultrasound. Occurrence of AEs within 3 months after treatment was recorded and categorized based on severity and the Clavien-Dindo classification.¹⁰ Dysuria was defined as an AE in patients who had penile burning and penile pain.

Study parameters were described using descriptive statistics. Changes in outcome measures from baseline to follow-up were compared using a two-tailed paired Student's t-test. One-way analysis of variance (ANOVA) test or two-tailed two-sample Student's t-test was used to compare numerical variables between cohorts. Pearson chi-square test or Fisher's exact test was used to compare categorical variables between cohorts. The impact of the number of injections on numerical and categorical variables was assessed using multiple linear regression and multiple logistic regression models, respectively, after adjusting for confounders at baseline. Multiple regression analyses were adjusted for age, history of urinary retention, baseline PSA, baseline prostate volume, prostatic urethral length, and presence of median lobe. p values of <0.05 were considered statistically significant. Data were analyzed using R Programming version 4.1.2.

Results

A total of 179 patients were included: 58, 91, 22, and 8 in the 1, 2, 3, and 4 injections cohorts, respectively (Fig. 1). The 1 injection cohort was significantly younger (60.9 ± 8.3 years) than the 2 (64.7 ± 7.9 years), 3 (64.7 ± 9.1 years), and 4 (65.8 ± 9.7 years) injections cohorts (p = 0.038). A greater proportion of patients in the 4 injections cohort had a previous history of urinary retention (50.0%) when compared to the other cohorts (1 injection: 1.7%; 2 injections: 3.3%; 3 injections: 9.1%, p < 0.001).

FIG. 1.

Flowchart of study cohort of 179 patients who were treated with Rezum.

The 1 injection cohort had a significantly lower mean baseline PSA (1.2 ± 1.2 ng/mL) and prostate volume (34.4 ± 11.4 cc) when compared to the other cohorts (p < 0.001). The presence of a median lobe was more common in the 2 (70.3%), 3 (90.9%), and 4 (75.0%) injections cohorts when compared to the 1 injection cohort (55.2%, p = 0.018). Mean prostatic urethral length was the shortest in the 1 injection cohort (2.1 ± 0.5 cm) and the longest in the 4 injections cohort (3.7 ± 0.7 cm, p < 0.001) (Table 1).

Table 1.

Baseline Demographics and Characteristics

Demographic/characteristic	All patients	No. of injections				p
Demographic/characteristic	All patients	1	2	3	4	p
N	179	58	91	22	8
Age (years), mean (SD, N)	63.6 (8.4, 179)	60.9 (8.3, 58)	64.7 (7.9, 91)	64.7 (9.1, 22)	65.8 (9.7, 8)	0.038
Race/ethnicity, n/N (%)						0.487
Non-Hispanic White	25/179 (14.0)	8/58 (13.8)	13/91 (14.3)	3/22 (13.6)	1/8 (12.5)
Non-Hispanic Black	56/179 (31.3)	12/58 (20.7)	33/91 (36.3)	7/22 (31.8)	4/8 (50.0)
Hispanic	37/179 (20.7)	11/58 (19.0)	19/91 (20.9)	6/22 (27.3)	1/8 (12.5)
Asian	61/179 (34.1)	27/58 (46.6)	26/91 (28.6)	6/22 (27.3)	2/8 (25.0)
Medical history, n/N (%)
Hypertension	103/179 (57.5)	29/58 (50.0)	53/91 (58.2)	16/22 (72.7)	5/8 (62.5)	0.317
Erectile dysfunction	86/179 (48.0)	25/58 (43.1)	48/91 (52.7)	10/22 (45.5)	3/8 (37.5)	0.617
Dyslipidemia	68/179 (38.0)	18/58 (31.0)	39/91 (42.9)	10/22 (45.5)	1/8 (12.5)	0.184
Diabetes mellitus	57/179 (31.8)	17/58 (29.3)	31/91 (34.1)	7/22 (31.8)	2/8 (25.0)	0.908
Nephrolithiasis	16/179 (8.9)	6/58 (10.3)	8/91 (8.8)	2/22 (9.1)	0/8 (0)	0.818
Urinary retention	10/179 (5.6)	1/58 (1.7)	3/91 (3.3)	2/22 (9.1)	4/8 (50.0)	<0.001
IPSS, mean (SD, N)	19.6 (6.8, 179)	20.5 (7.1, 58)	19.2 (6.9, 91)	18.6 (6.4, 22)	21.1 (5.6, 8)	0.539
QoL, mean (SD, N)	4.5 (1.3, 177)	4.6 (1.3, 58)	4.4 (1.3, 89)	4.4 (0.8, 22)	4.6 (1.2, 8)	0.744
PSA (ng/mL), mean (SD, N)	2.9 (4.3, 179)	1.2 (1.2, 58)	2.9 (3.0, 91)	5.1 (8.3, 22)	9.3 (7.7, 8)	<0.001
Qmax (mL/s), mean (SD, N)	11.4 (5.9, 139)	12.2 (5.2, 49)	11.5 (6.5, 73)	8.7 (4.0, 13)	9.9 (7.6, 4)	0.160
PVR (mL), mean (SD, N)	40.9 (99.8, 91)	42.7 (99.4, 27)	49.3 (115.2, 47)	14.7 (33.5, 11)	15.4 (23.8, 6)	0.689
IIEF—erectile function, mean (SD, N)	15.9 (8.3, 111)	15.9 (8.3, 37)	16.4 (8.5, 55)	13.9 (8.2, 14)	16.8 (9.1, 5)	0.351
IIEF—orgasmic function, mean (SD, N)	6.2 (3.0,110)	6.5 (2.9, 37)	6.4 (3.1 54)	5.1 (3.1, 14)	5.4 (2.6, 5)	0.893
Prostate volume (cc), mean (SD, N)	48.8 (26.9, 179)	34.4 (11.4, 58)	49.4 (18.3, 91)	64.0 (19.7, 22)	103.0 (78.3, 8)	<0.001
Prostate volume breakdown, n/N (%)						0.748
<30 cc	27/179 (15.1)	8/58 (13.8)	13/91 (14.3)	5/22 (22.7)	2/8 (25.0)
30–80 cc	139/179 (77.7)	44/58 (75.9)	73/91 (80.2)	16/22 (72.7)	5/8 (62.5)
>80 cc	13/179 (7.2)	6/58 (10.3)	5/91 (5.5)	1/22 (4.6)	1/8 (12.5)
Prostatic urethral length (cm), mean (SD, N)	2.5 (0.6, 179)	2.1 (0.5, 58)	2.5 (0.3, 91)	3.3 (0.3, 22)	3.7 (0.7, 8)	<0.001
Presence of median lobe, n/N (%)	122/179 (68.2)	32/58 (55.2)	64/91 (70.3)	20/22 (90.9)	6/8 (75.0)	0.018
Previous BPH procedure/surgery, n/N (%)	51/179 (28.5)	14/58 (24.1)	27/91 (29.7)	6/22 (27.3)	4/8 (50.0)	0.487
Alpha blockers and/or 5-ARIs usage, n (%)	162/179 (90.5)	52/58 (89.7)	81/91 (89.0)	21/22 (95.5)	8/8 (100)	0.626

Bolded values indicate p < 0.05.

p Value for Qmax is calculated between the 1, 2, and 3 injections cohorts.

5-ARIs = 5-alpha reductase inhibitors; BPH = benign prostatic hyperplasia; IIEF = International Index of Erectile Function; IPSS = International Prostate Symptom Score; PSA = prostate-specific antigen; PVR = postvoid residual; Qmax = maximum urinary flow rate; QoL = quality of life; SD = standard deviation.

All patients were catheterized for a mean of 4.8 ± 1.4 days. Patients who received 4 injections were catheterized for a longer period than those who received less injections (1 injection: 4.4 ± 0.7 days; 2 injections: 4.7 ± 0.8 days; 3 injections: 4.8 ± 0.4 days; 4 injections: 8.3 ± 4.2 days, p < 0.001). Furthermore, patients who had a mean baseline prostate volume >80 cc were catheterized for a longer period than those who had a mean baseline prostate volume <30 cc or 30–80 cc (<30 cc: 4.6 ± 0.6 days; 30–80 cc: 4.7 ± 1.0 days; >80 cc: 6.6 ± 3.5 days, p < 0.001).

At 3 months, all cohorts saw significant mean changes in IPSS (−9.7 ± 7.9) and QoL (−1.9 ± 1.9) and improvements remained durable to 12 months (p < 0.05). At 6 months, the 2 injections cohort saw a significantly greater mean change in Qmax (10.2 ± 10.1 mL/s) when compared to the 1 injection cohort (0.6 ± 4.6 mL/s, p = 0.015). There were no significant differences in mean changes in IPSS, QoL, PVR, IIEF—Erectile Function, and IIEF—Orgasmic Function between the cohorts at any follow-up (p > 0.05) (Table 2).

Table 2.

Changes in Outcome Measures Over Time

Outcome measure	All patients	No. of injections				p
Outcome measure	All patients	1	2	3	4	p
1-Month
Change in IPSS, mean (SD, N)	−6.8 (7.3, 146)^***	−7.7 (7.9, 48)^***	−7.1 (6.8, 75)^***	−3.7 (6.8, 18)^*	−3.6 (7.4, 5)	0.157
Change in QoL, mean (SD, N)	−1.3 (1.9, 146)^***	−1.4 (1.8, 48)^***	−1.3 (1.9, 75)^***	−0.9 (1.8, 18)^*	−1.2 (3.0, 5)	0.825
3-Month
Change in IPSS, mean (SD, N)	−9.7 (7.9, 151)^***	−9.4 (9.1, 47)^***	−9.7 (7.5, 77)^***	−9.9 (7.5, 20)^***	−11.3 (6.8, 7)^**	0.946
Change in QoL, mean (SD, N)	−1.9 (1.9, 149)^***	−1.7 (2.0, 47)^***	−2.1 (1.9, 75)^***	−2.1 (1.8, 20)^***	−2.1 (2.2, 7)^*	0.693
Change in Qmax (mL/s), mean (SD, N)	5.3 (6.5, 28)^***	4.5 (5.0, 8)^*	4.4 (6.9, 15)^*	10.0 (9.6, 3)	8.1 (3.3, 2)	0.969
Change in PVR (mL), mean (SD, N)	−27.5 (103.8, 58)	−48.9 (124.3, 17)	−23.8 (104.7, 32)	5.0 (42.8, 6)	−10.6 (33.3, 3)	0.535
6-Month
Change in IPSS, mean (SD, N)	−10.2 (7.8, 142)^***	−8.5 (7.7, 45)^***	−10.4 (7.7, 72)^***	−12.2 (8.8, 19)^***	−15.3 (4.8, 6)^***	0.114
Change in QoL, mean (SD, N)	−2.2 (1.9, 140)^***	−1.9 (1.9, 45)^***	−2.3 (1.9, 70)^***	−2.2 (1.5, 19)^***	−3.2 (2.5, 6)^*	0.422
Change in Qmax (mL/s), mean (SD, N)	4.7 (8.2, 23)^*	0.6 (4.6, 10)	10.2 (10.1, 9)^*	2.2 (2.7, 3)	5.1 (n/a, 1)	0.015
Change in PVR (mL), mean (SD, N)	−22.6 (111.6, 40)	−50.5 (141.6, 11)	−24.4 (102.8, 22)	47.2 (85.7, 5)	−23.9 (33.8, 2)	0.291
Change in IIEF—Erectile function, mean (SD, N)	−0.2 (7.3, 45)	−0.9 (6.7, 14)	−0.6 (8.4, 20)	2.0 (7.2, 8)	0.0 (1.0, 3)	0.659
Change in IIEF—Orgasmic function, mean (SD, N)	−0.4 (3.5, 43)	−1.8 (3.3, 13)	−0.3 (3.5, 19)	1.5 (3.7, 8)	−0.3 (0.6, 3)	0.110
12-Month
Change in IPSS, mean (SD, N)	−9.6 (8.7, 133)^***	−9.3 (8.9, 40)^***	−9.5 (8.6, 70)^***	−10.6 (10.2, 18)^***	−10.0 (5.6, 5)^*	0.961
Change in QoL, mean (SD, N)	−2.2 (1.9, 132)^***	−2.0 (1.9, 40)^***	−2.2 (1.9, 69)^***	−2.3 (1.9, 18)^***	−2.6 (2.1, 5)^*	0.858
Change in Qmax (mL/s), mean (SD, N)	4.1 (6.6, 34)^***	4.4 (3.0, 6)^*	3.4 (7.1, 23)^*	7.3 (8.7, 4)	6.3 (n/a, 1)	0.739
Change in PVR (mL), mean (SD, N)	−24.4 (85.6, 59)	−12.9 (118.6, 19)	−34.9 (75.5, 28)^*	−17.9 (36.5, 9)	−18.6 (25.6, 3)	0.687
Change in IIEF—Erectile function, mean (SD, N)	−1.0 (10.9, 29)	3.1 (10.4, 9)	−5.5 (12.2, 13)^*	2.2 (7.6, 5)	1.5 (0.7, 2)	0.163
Change in IIEF—Orgasmic function, mean (SD, N)	−1.4 (3.4, 29)	−2.1 (4.5, 9)	−1.7 (3.0, 13)	0.0 (2.4, 5)	0.0 (1.4, 2)	0.555

Bolded values indicate p < 0.05.

p Values for changes in IPSS and QoL are calculated across all cohorts. p Values for change in Qmax are calculated between the 1 and 2 injections cohorts. p Values for change in PVR, IIEF Erectile Function, and IIEF Orgasmic Function are calculated between the 1, 2, and 3 injections cohorts.

p < 0.05 when compared to baseline; ^** p < 0.01 when compared to baseline; ^*** p < 0.001 when compared to baseline.

Serious AEs (Clavien-Dindo Grade IV) occurred in two patients (2.2%), both of whom were transported to the hospital following postoperative vasovagal syncope. Nonserious AEs occurred in 140 patients (78.2%) and were classified as either Clavien-Dindo Grade I or II. The most common AE was gross hematuria (69.8%), followed by penile burning (65.8%) and penile pain (35.1%). The rate of gross hematuria was significantly lower in the 1 injection cohort (53.2%) when compared to that in the 2 (74.7%), 3 (90.0%), and 4 (71.4%) injections cohorts (p = 0.012). The rate of UTI was significantly higher in the 4 injections cohort (37.5%) when compared to that in the 1 (3.4%), 2 (7.7%), and 3 (4.5%) injections cohorts (p = 0.006) (Table 3).

Table 3.

Overview of Adverse Events

AE	All patients	No. of injections				p
AE	All patients	1	2	3	4	p
Serious
Vasovagal	2/179 (1.1)	0/58 (0)	2/91 (2.2)	0/22 (0)	0/8 (0)	n/a
Sepsis	0/179 (0)	0/58 (0)	0/91 (0)	0/22 (0)	0/8 (0)	n/a
Nonserious
Hematuria, gross	104/149 (69.8)	25/47 (53.2)	56/75 (74.7)	18/20 (90.0)	5/7 (71.4)	0.012
Penile burning	98/149 (65.8)	28/46 (60.9)	49/76 (64.5)	14/20 (70.0)	7/7 (100)	0.226
Penile pain	52/148 (35.1)	17/45 (37.8)	24/76 (31.6)	7/20 (35.0)	4/7 (57.1)	0.563
Dysuria	40/147 (27.2)	12/44 (27.3)	18/76 (23.7)	6/20 (30.0)	4/7 (57.1)	0.293
Sloughing	30/112 (26.8)	6/39 (15.4)	17/53 (32.1)	6/16 (37.5)	1/4 (25.0)	0.232
Urinary retention	26/179 (14.5)	8/58 (13.8)	10/91 (10.9)	5/22 (22.7)	3/8 (37.5)	0.137
UTI (confirmed)	13/179 (7.7)	2/58 (3.4)	7/91 (7.7)	1/22 (4.5)	3/8 (37.5)	0.006

Bolded values indicate p < 0.05.

Data presented as n/N (%).

AE = adverse event; UTI = urinary tract infection.

With respect to rates of postoperative urinary retention, there was no significant difference in baseline prostate volume groups between those who underwent urinary retention and those who did not (retention patients <30 cc: 11.5%; 30–80 cc: 80.8%; >80 cc: 7.7% vs nonretention patients <30 cc: 15.7%; 30–80 cc: 77.1%; >80 cc: 7.2%, p = 0.861). A total of 8/179 patients (4.5%) were surgically retreated within 12 months; 2 (3.7%), 3 (3.4%), 1 (4.5%), and 2 (25.0%) from the 1, 2, 3, and 4 injections cohorts, respectively. A significantly higher proportion of patients were surgically retreated in the 4 injections cohort when compared to the other cohorts (p = 0.048).

At 3 months, 104/130 of all patients (80.0%) discontinued their BPH medications. There were no significant differences between the cohorts in BPH medication discontinuation at 3 months (32/41 [78.0%], 53/65 [81.5%], 16/19 [84.4%], and 3/5 [60.0%] for 1, 2, 3, and 4 injections cohorts, respectively, p = 0.647). At 12 months, 83/105 of all patients (79.0%) discontinued their BPH medications. There were no significant differences between the cohorts in BPH medication discontinuation at 12 months (27/31 [87.1%], 39/52 [75.0%], 16/17 [94.1%], and 4/5 [80.0%] for 1, 2, 3, and 4 injections cohorts, respectively, p = 0.266).

Between 3 and 6 months, 143 patients had a transrectal ultrasound of the prostate, with 44, 75, 19, and 5 patients in the 1, 2, 3, and 4 injections cohorts, respectively. Mean percentage change in prostate volume across all cohorts was −27.3% ± 18.2% (p < 0.001), with each cohort experiencing significant percent changes in prostate volume (1 injection: −26.1% ± 14.4%; 2 injections: −27.3% ± 21.6%; 3 injections: −28.8% ± 12.0%; 4 injections: −32.2% ± 23.9%, p < 0.05). There were no significant differences in mean percentage changes in prostate volume between the cohorts (p = 0.881).

Furthermore, mean cc changes in prostate volume across all cohorts was −12.9 ± 11.5 cc (p < 0.001), with each cohort experiencing significant mean cc changes in prostate volume (1 injection: 8.7 ± 5.7 cc; 2 injections: 13.4 ± 13.8 cc; 3 injections: 18.1 ± 6.8 cc; 4 injections: 23.0 ± 13.2 cc, p < 0.05). There were significant differences in mean cc changes in prostate volume between the cohorts (p = 0.003).

Out of the 143 patients who had a transrectal ultrasound of the prostate between 3 and 6 months, 68 (47.6%) had a volume reduction of ≥30% and 75 (52.4%) had a volume reduction of <30%. There were no significant differences between the volume reduction ≥30% group and volume reduction <30% group with respect to baseline demographics/characteristics and procedural characteristics (Supplementary Table S1). Regarding sexual function, there was no significant difference in baseline prostate volume between patients who saw a negative change and those who are a positive or no change in IIEF—Erectile Function and IIEF—Orgasmic Function at 6 and 12 months (Supplementary Table S2).

Multiple linear regression analysis revealed that the number of injections did not significantly predict changes in IPSS, QoL, and PVR at any follow-up (p > 0.05), but significantly predicted change in Qmax at 3 months (β = 5.7, p = 0.019). Multiple logistic regression showed that for each additional injection, the odds of gross hematuria, penile burning, penile pain, and dysuria increased by 3.8 (95% confidence interval [CI] 1.7–9.1), 2.6 (95% CI 1.2–5.9), 2.2 (95% CI 1.1–4.9), and 3.0 (95% CI 1.3–7.5), respectively (Table 4).

Table 4.

Multiple Regression Analysis of Number of Injections on Outcome Measures Over Time and Adverse Events

Outcome measure	β	95% CI	p
1-Month
Change in IPSS	1.1	−1.3 to 3.5	0.360
Change in QoL	0.1	−0.5 to 0.7	0.840
3-Month
Change in IPSS	−0.1	−2.6 to 2.5	0.980
Change in QoL	−0.1	−0.7 to 0.5	0.730
Change in Qmax (mL/s)	5.7	1.0 to 10.3	0.019
Change in PVR (mL)	22.6	−31.2 to 76.3	0.400
6-Month
Change in IPSS	−1.5	−4.2 to 1.1)	0.250
Change in QoL	−0.6	−1.2 to 0.1	0.080
Change in Qmax (mL/s)	2.4	−6.8 to 11.6	0.590
Change in PVR (mL)	27.6	−58.5 to 113.7	0.520
Change in IIEF—Erectile Function	1.8	−3.3 to 6.8	0.485
Change in IIEF—Orgasmic function	0.7	−1.6 to 3.0	0.932
12-Month
Change in IPSS	−0.8	−3.9 to 2.4	0.620
Change in QoL	0.0	−0.7 to 0.7	0.990
Change in Qmax (mL/s)	−2.1	−8.9 to 4.6	0.530
Change in PVR (mL)	−7.2	−55.2 to 40.8	0.770
Change in IIEF—Erectile Function	−0.4	−11.1 to 10.2	0.932
Change in IIEF—Orgasmic function	0.1	−2.8 to 3.0	0.961
AE	OR	95% CI	p
Serious
Vasovagal	4.8	0.2 to 151.2	0.320
Sepsis	n/a	n/a	n/a
Non-serious
Hematuria, gross	3.8	1.7 to 9.1	0.001
Penile burning	2.6	1.2 to 5.9	0.015
Penile pain	2.2	1.1 to 4.9	0.039
Dysuria	3.0	1.3 to 7.5	0.011
Sloughing	2.1	0.8 to 5.6	0.130
Urinary retention	1.5	0.7 to 7.3	0.320
UTI (confirmed)	2.2	0.7 to 3.6	0.190

Bolded values indicate p < 0.05.

Multiple regression analysis adjusted for age, history of urinary retention, baseline PSA, baseline prostate volume, prostatic urethral length, and presence of median lobe.

CI = confidence interval; OR = odds ratio.

Multiple logistic regression also showed that for each additional injection, the odds of discontinuing BPH medications at 3 months decreased by 64% (95% CI 0.1–0.9). However, at 12 months, each additional injection did not significantly affect the odds discontinuing BPH medications (odds ratio [OR]: 0.8, 95% CI 0.4–3.2). Moreover, each additional injection did not significantly affect the odds of getting surgically retreated within 12 months postoperatively (OR: 1.1, 95% CI 0.2–4.6). Multiple linear regression analysis revealed that the number of injections significantly predicted changes in percent change in prostate volume (β = −7.9, p = 0.009) and cc change in prostate volume (β = −3.8, p = 0.035).

Discussion

To our knowledge, this study is the first to assess the efficacy and safety of Rezum outcomes with respect to the number of injections used during treatment. Our findings suggest that using more injections did not improve LUTS to a greater degree, but rather increased the odds of AEs, including gross hematuria, penile burning, penile pain, and dysuria. Furthermore, patients who received more injections were less likely to discontinue their BPH medications at 3 months.

Recently, Aladesuru et al prospectively assessed Rezum outcomes through a “less is more” treatment approach, which involved using a single injection per prostatic lobe.¹¹ The authors concluded that improvements in IPSS, QoL, and Qmax with a “less is more” treatment approach was similar to those seen in Rezum's randomized control trial (RCT) by McVary et al, which utilized a traditional treatment approach of using injections based on prostatic urethral length.^2,11 Similarly, the reductions in IPSS and QoL across the injection cohorts observed in our study at 12 months were comparable to the reductions observed in the RCT at 12 months (RCT IPSS: −11.7 ± 7.2, QoL: −2.3 ± 1.5).² Importantly, our study did not observe a relationship between the number of injections and reductions in IPSS and QoL at any follow-up.

There was an increase in the odds of gross hematuria, penile burning, penile pain, and dysuria with each additional injection utilized. A single injection delivers water vapor at 103°C for 9 seconds into the prostatic lobes, which results in disruption of cell membranes and eventual cell necrosis.¹² Therefore, presumably, using more injections results in a larger amount of cell necrosis, a greater degree of inflammation and tissue edema, and consequently an increase in the occurrence of AEs. Furthermore, additional injections in our study were associated with a smaller number of patients discontinuing their BPH medications at 3 months postoperatively. It is plausible that because additional injections resulted in an increase in AEs, those patients may experience more bothersome LUTS and therefore may require continuation of their BPH medications at 3 months. However, at 12 months, this trend was not observed likely due to the resolution of AEs.

A total of 78.2% of patients in our study experienced nonserious AEs, which is considerably higher than the rates reported from the RCT (39.0%) and from the study by Aladesuru et al (12.5%).^1,2,11 Some of the AEs in our study, such as gross hematuria and penile burning, can be expected due to the endoscopic nature of Rezum and/or from the insertion of a Foley catheter after treatment. However, this observation may also be due to our broad definitions of certain AEs. For example, we defined gross hematuria as any visual trace of blood in the Foley catheter drainage bag after postoperative Foley catheter insertion or at any point during urination after catheter removal.

Penile burning was defined as any irritation felt in the penis after the procedure. More importantly, we collected AEs proactively by asking every patient a set of scripted questions regarding the occurrence of specific AEs. There is a risk of underreporting of AEs from passive data collection when compared to proactive collection.¹³

Our study observed a surgical retreatment rate of 4.7% at 12 months, which is comparable to previously reported Rezum retreatment rates at 12 months.¹ Interestingly, in our study, patients who received less injections were not more likely to get surgically retreated. These results suggest that retreatment after Rezum may not be due to inadequate or incomplete treatment. However, this needs to be investigated further with a larger sample of surgically retreated patients and at a longer follow-up.

The number of injections used was largely 1 injection per cm of prostatic urethral length. Although larger prostates generally received more injections than smaller prostates, there were cases of larger prostates receiving less injections than smaller prostates and vice versa. This was primarily due to the unique anatomy of the patient's prostate and prostatic urethral length, in which the size of the prostate was not always correlated with prostatic urethral length.

Each injection per lateral lobe reduced prostate volume by 3.8 cc or 7.9%. However, the greater degree of reduction in prostate volume from utilizing more injections did not result in greater improvements in IPSS. Numerous studies have shown weak or no correlations between prostate volume and IPSS.^14
–16 The absence of correlations between prostate volume and IPSS may be due to the age-related changes in the urinary bladder, which can result in bladder outlet obstruction.¹⁷ In addition, instead of prostate volume, IPSS may be related to intrinsic prostate tension from the contraction of prostatic smooth muscle and/or extrinsic tension of the capsule from hyperplasia of the prostatic transition zone.¹⁸

Nevertheless, given that using more injections resulted in greater reductions in prostate volume but not greater improvements in IPSS, it is questionable whether one of the goals of Rezum should be to optimize prostate volume reduction. Instead, causing prostate tissue necrosis with fewer injections may provide similar relief in LUTS as with more injections.

Despite its merits and novelty, this study is not without limitations. First, the sample size in the 4 injections cohort and follow-up time point for some outcome measures were small, which resulted in only being able to analyze Qmax outcomes between the 1 and 2 injections cohorts and PVR and IIEF outcomes between the 1, 2, and 3 injections cohorts. Second, although patients were stratified into cohorts based on the number of injections used per lateral lobe, some patients received additional injections if they had a median lobe. However, we adjusted for this in the multiple linear and multiple logistic regression analyses.

Finally, the urologists performing the procedure used injections based on the patient's prostatic urethral length and prostate volume. Although these variables were adjusted for in the multiple linear and multiple logistic regression models, a double-blinded study is warranted, in which a variable number of injections are used regardless of the prostatic urethral length and prostate volume. Despite these limitations, the presented study is the first to assess the relationship between the number of injections and Rezum outcomes and suggest an alternative safer treatment approach to Rezum.

Conclusion

Using more injections during Rezum treatment did not result in greater improvement in LUTS and QoL, but instead, increased the odds of AEs. Through a more favorable safety profile as a result utilizing fewer injections, patient satisfaction and urologist adoption of this novel technology may increase. In addition, utilizing less injections may decrease perioperative time and health care costs associated with a longer Rezum procedure. Nevertheless, a RCT is warranted to directly assess Rezum outcomes in patients receiving standard treatment vs fewer injections treatment to confirm if “less is more.”

Footnotes

Acknowledgments

We thank Dr. David S. Schnapp for helping to create the database and the staff at DSS Urology for providing assistance throughout the period of data collection. We also thank Denzel Zhu for helpful comments regarding study design and analysis.

Data Availability Statement

The data to support this study are not publicly available since they contain potentially identifiable patient information. Deidentified data are available from the corresponding author by reasonable request.

Ethics Approval Statement

The Western Institutional Review Board approved of this study under protocol #1-1181739-1.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplementary Material

Supplementary Table S1

Supplementary Table S2

Abbreviations Used

References

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