Aquablation for BPH

We want to understand the advantages and disadvantages of aquablation for using the waterjet technology for treating BPH symptoms. Currently, there is very little real world experience out there. Fortunately, there are two international trials (US, United Kingdom, New Zealand and Australia) on aquablation  using TURP as control. The names for the trials are Water (for prostrate 30-80 cc) and Water II (for prostate 80-150 cc).

The results from these two trials contain the most up to date knowledge of aquablation. If u are considering aquablation or just want to know if aquablation could be a future candidate to treat ur symptoms, u may not want to miss these reports as they contain detailed info about  complications which is critical for making decision. If we understand the pros and cons of all BPH intervention technologies, we are more likely able to pick the best technology to relieve our symptoms. Aquablation is the newest technology and deserve our fullest attention.

The 6 mo results for the WATER trial is given in the paper,

"WATER: A Double-Blind, Randomized, Controlled Trial of Aquablation® vs Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia," by Peter Gilling et al. published in journal of urology in May, 2018.

What Was the Trial All About?

This paper was written by 19 MDs. The trials were supported by the equipment manufacturer and some of the authors had financial relationship with the manufacturer. But with 19 authors, the report does not appear to be biased.

"A total of 275 subjects were evaluated at 17 sites in the United States, United Kingdom, Australia and New Zealand between October 2015 and December 2016. ...Baseline characteristics were well balanced across the groups and consistent with moderate to severe BPH (table 1). Mean prostate size was 53 ml and 81% of the men were sexually active....., leaving 181 in the intent to treat population (fig. 1)."

"Subjects were assigned at random in a 2:1 ratio to Aquablation (121 patients) or TURP (60 patients) ....stratified by study site....."

What BPH Intervention Technologies  Were Used in the Trial?

Aquablation and Mono and bipolar TURP were the technologies used in the trial.

"Aquablation was performed using the AquaBeam® System.13 A 24Fr hand piece probe similar to a rigid cystoscope was inserted in the prostatic urethra and locked into place using a bed mounted, rigid arm. Under real-time prostate visualization with transrectal ultrasound the surgeon used a console to mark the target resection contour. Under surgeon control tissue ablation was performed robotically with a high velocity water jet to resect adenomatous tissue while avoiding the verumontanum and the ejaculatory ducts.

(Note: special effort is make to preserve normal ejaculation.)

After Aquablation was complete, hemostasis was achieved using focal, nonresective electrocautery or low pressure inflation of a Foley balloon catheter in the prostatic fossa.16 Catheterization and bladder irrigation were left to local investigator discretion. Otherwise post treatment management, which included continuous bladder irrigation in all subjects, was similar across groups." 

(Note : not all Aqua patients were treated with heatless balloon for haemostasis.)

"After TURP a urethral urinary catheter was placed and patients received continuous bladder irrigation. Catheter choice and bladder irrigation duration were in accordance with local preferences at each site."

"The index study procedure was performed using general anesthesia in 94% of cases and spinal anesthesia in 6%. For TURP monopolar and bipolar loops were used in 36 (55.4%) and in 29 cases (44.6%), respectively."

Study End Points 

1) "The study primary efficacy end point was the change in I-PSS from baseline to 6 months"

2) "The study primary safety end point was the proportion of subjects with adverse events rated by the clinical events committee as possibly, probably or definitely related to the study procedure, classified as Clavien-Dindo grade 2 or higher or any grade 1 event resulting in persistent disability, such as ejaculatory or erectile dysfunction or incontinence, as evidenced through 3 months after treatment."

3) Secondary end points 

"included resection time and total operative time, hospital stay, the reoperation or repeat intervention rate, 

the proportion of sexually active subjects who reported worsening sexual function through 6 months on IIEF-5 (6-point decrease19) or MSHQ-EjD (2-point decrease20) and the proportion of subjects with a serious device or procedure related adverse event. 

.... Since IIEF and MSHQ assume that a man is sexually active, those who were not sexually active at baseline or the study visit were excluded from this analysis. "

4) "Additional end points included a change in incontinence measured by the Incontinence Severity Index,21 pelvic pain, quality of life using EQ-5D (EuroQOL-5D),22 bladder catheterization duration, Work Productivity and Activity Impairment,23 and the relationship between the prostate size reduction measured on transrectal ultrasound and the change in symptoms scores. The latter will be reported elsewhere."

Results

(Note: Safety end point was evaluated up to month 3 whereas efficacy end point was evaluated up to month 6.)

How Long Was The Operation?

"Mean operative time, defined as pretreatment visualization to indwelling catheter insertion after resection was complete, was similar in the Aquablation and TURP groups (33 and 36 minutes, respectively, table 1). Mean resection time from first pedal activation to the end of pedal use was lower in the Aquablation group (4 vs 27 minutes). Resection time strongly depended on prostate size in TURP with 0.3 minutes per additional gm of prostate size but only modestly in Aquablation with 0.04 minutes per additional gm." 

(Note: it isn't clear how long the waterjet was in the patient's prostate.)

Hemoglobin Drop and Amount of Fluid Used For Irrigation

"Postoperative hemoglobin decreased from 14.9 to 13.0 in the Aquablation group and from 14.7 to 13.7 in the TURP group . One Aquablation case but no TURP case required blood transfusion. 

(Note: Aqua could require blood transfusion.)

Less irrigation fluid was used intraoperatively during Aquablation compared to TURP (5.2 vs 13.2 L). "

Hospital Stay and Catheter Time

"Mean hospital stay was 1.4 days in each group with no geographic variation and the urinary catheter was removed a median of 1 day after surgery in each group." 

(Note: if surgery took 0.4 day, that means the catheter was removed by the time the patient left the hospital. The length of hospital stay time and catheter removal time are comparable to HoLEP. Not sure how they managed to do that.)"

How Much IPSS and QoL Improvements By Month 6?

At month 1 significant symptoms were relieved as evidenced from IPSS, QoL, Qmax and PVR, and at month 3, all these parameters were nearly at their final values. 

"At 6 months mean I-PSS had decreased from baseline by 16.9 points for Aquablation and 15.1 points for TURP (fig. 2). The mean difference in the change score at 6 months was 1.8 points greater for Aquablation ....(further) Men with a prostate greater than 50 ml had (even greater) superior improvement in I-PSS after Aquablation than after TURP."

"The I-PSS quality of life score improved similarly in the Aquablation and TURP groups at 6 months with a decrease of 3.5 vs 3.3 points. At month 3 the decrease was statistically larger in the Aquablation group."

Overall Safety at Month 3

"The 3-month primary safety end point rate was lower in the Aquablation group than in the TURP group (26% vs 42%, fig. 3). The rate of persistent grade 1 events at month 3 was also lower after Aquablation (7% vs 25%) and the rate of grade 2 and greater events was similar in the 2 groups at 20% for Aquablation and 23% for TURP ( table 2). Safety results remained consistent at 6 months. "

(Note: not sure what "consistent" meant.  it didn't say after month 3, how many adversed events were resolved?)

Among sexually active men without the condition at baseline anejaculation was less common after Aquablation than after TURP (10% vs 36%). The anejaculation rate after Aquablation was somewhat lower when posttreatment cautery was avoided (7% vs 16%)."

Primary Safety:  25%A/41.5%T

CD1P:               6.9%A/24.6%T

CD2+:             19.8%A/23.1%T

A=Aquablation , T=TURP

"Figure 3. Safety outcome in all patients. CD1P, incontinence, erectile dysfunction and ejaculatory dysfunction. CD2+, all Clavien-Dindo grade 2-5 events. "

Breakdown OF Complications (The Most Important Info)

"Table 2. Events at month 3 categorized by Clavien-Dindo grades by group as possibly, probably or definitely related to procedure and/or device

Format: (# of events)/#( of patients) 

Listing Order: Aquablation,  TURP

CD Events                Aqua(120 pts)  TURP(60 pts)

Grade 1:              63/39 (33.6%)   41/27 (41.5%)

 Bladder spasm         3/3                   1/1    

 Bleeding                   12/11       7/7    

 Dysuria                   12/12       5/5    

 Pain                                 5/5                   3/3    

 Retrograde 

    ejaculation                     8/8                 16/16    

 Urethral damage             1/1                   1/1    

 Urinary retention        11/9                4/4    

 Urinary tract 

       infection                      2/2                   0/0    

 Urinary urgency, 

         frequency, 

       difficulty, leakage          4/4                   1/1    

 Other                                 5/5                3/3    

Grade 2:              20/19 (16.4%)    15/11 (16.9%)    

 Bladder spasm         4/4                   2/2    

 Bleeding                     1/1                   0/0    

 Dysuria                     0/0                   1/1    

 Pain                                1/1                   2/2    

 Urinary tract

       infection                     9/9                   5/5

 Urinary urgency, 

 frequency, difficulty, 

      leakage                      2/2                   3/2    

 Other                                  3/3                   2/2    

Grade 3a:                  4/4 (3.4%)      2/2 (3.1%)

 Bleeding                      1/1               1/1    

 Urethral stricture 

       or adhesions          3/3                1/1    

Grade 3b:                    3/3 (2.6%)       3/3 (4.6%)    

 Bleeding                       2/2         2/2

 Urethral stricture 

       or adhesions            0/0          1/1    

 Urinary retention            1/1          0/0    

Grade 4:                     1/1 (0.9%)          0/0    (0%)

 Arrhythmia                         1/1                 0/0

(Total percentage               56.9%           66.1     )"

For Postrate Size 50-80 cc (Note: Increditable, 2% Retrograde Ejaculation!)

"In men with a prostate greater than 50 ml the primary safety end point was lower after Aquablation than after TURP (20% vs 46%, fig. 4). The rate of persistent grade 1 events was substantially lower (2% vs 26%) and the rate of Clavien-Dindo grade 2 and greater events trended in favor of Aquablation (19% vs 29%). Among sexually active men without the condition at baseline anejaculation was less common after Aquablation than after TURP (2% vs 41%).

(Note: don't understand why aquablation was so much safer for larger prostrate. Also note 2%  anejaculation for Aqua.)"

Primary Safety:  20.3%A/45.7%T

CD1P:                  1.6%A/25.7%T

CD2+:                18.8%A/28.6%T

"Figure 4. Posttreatment findings in patients with baseline prostate size between 50 and 80 ml. I-PSS change after Aquablation (blue curve) and TURP (red curve). Safety outcomes in patients with incontinence, erectile dysfunction and ejaculatory dysfunction (CD1P) and all Clavien-Dindo grade 2-5 events (CD2+). Blue bars represent Aquablation. Red bars represent TURP."

Additional Secondary End Points ( Back to Postrate Size 30-80 cc Again)

"Reoperation for BPH was performed in 1 TURP case but not in any Aquablation case. "

Sexually Related Results

"There were threshold decreases in MSHQ-EjD or IIEF-5 scores in 33% of Aquablation and 56% of TURP cases. In sexually active men mean erectile function scores on IIEF-15 were stable after Aquablation but decreased slightly after TURP except for overall sexual satisfaction, for which Aquablation was significantly better (fig. 5). Ejaculatory function scores on MSHQ-EjD were stable after Aquablation but significantly worse after TURP (fig. 6).

Figure 5. IIEF-15 subdomain score change by treatment and time. IIEF-15 comprises 15 questions with response ranging from 0 to 5. Erectile, intercourse satisfaction and all other domains are derived from 6 questions, 3 questions and 2 questions each, respectively. Overall satisfaction was superior in Aquablation group. NS, not significant. Blue curves indicate Aquablation. Red curves indicate TURP. (See figure in original paper.)

Figure 6. MSHQ-EjD score change by treatment and time in men who were sexually active at baseline and visit. Score was calculated using first 3 questions and ranged from 1—anejaculation to 15—normal ejaculation ability, strength and volume. Blue curve indicates Aquablation. Red curve indicates TURP. (See figure in original paper.)"

Flow Rate and Other End Points

"In each group the mean maximum urinary flow rate increased markedly from baseline to 6 months and mean post-void residual volume also decreased markedly (fig. 2). "

Amount of Tissue Removed

"The amount of tissue removed after TURP was 13 gm. Transrectal ultrasound performed preoperatively and at month 3 showed a smaller prostate size reduction for Aquablation (17.3 vs 24.0 cc, mean 31% vs 44% reduction). At 6 months PSA was decreased in the Aquablation group vs the TURP group (–1.2 vs –1.1 ng/ml, 30% vs 36% median reduction).

(Note: aquablation removed significantly less tissue(25-30%) than TURP, but yet has comparable  IPSS, Qmax and PVR. Less tissue removed could contribute to 10%  RE.)"

Incontinennce ISI Scores

"At 6 months mean incontinence symptom scores improved by 1.2 points in the Aquablation group and 0.6 in the TURP group. The mean score improvement at the 1, 3 and 6-month visits was 0.6 points greater in the Aquablation group.  

(Note: the ISI score is 0-12 points (the lower the better). Improvement of 1.2 points is not a significant change.  To get the ISI form, Google: christianacare org incontinence severity index.)"

Blood In Urine

"At 3 months dysuria frequency was similar but severity trended favorably toward Aquablation. Pelvic pain levels were low and similar throughout followup, and time off from work was brief in most cases."

Discussion

"In this trial ... water jet improved BPH related urinary symptoms noninferiorly compared to.... TURP. These improvements were seen across study sites where there had been no previous experience with Aquablation at 14 of the 17 sites.

Retrograde ejaculation after TURP is a common and accepted side effect caused by heat related damage to the ejaculatory duct.9 We observed a reduced rate of anejaculation after Aquablation compared to after TURP. The rate was even lower when post-Aquablation nonresective cautery was avoided. The decreased rate after Aquablation might be explained by tissue resection contours that were programmed to avoid damage near the verumontanum.

Improvements in objective urinary flow measures such as the maximum flow rate and post-void residual urine were in line with expectations for prostate resecting procedures. Moreover, other assessments of the acute impact of surgery, including hospital stay, work index and quality of life measurements, showed that Aquablation was well tolerated.

Other ablation technologies are available for the surgical treatment of moderate to severe BPH. Technologies providing high level improvement include resection techniques such as laser enucleation,24 TURP, laser photovaporization9 and Aquablation. Although it was not a direct comparison, improvements after Aquablation in our study appeared to be higher than after nonresective technologys, including convective water vapor energy (rezum®, 11 points higher)25, UroLift® procedure (11 points)26 and microwave thermotherapy (11 points27, 28) as well as after single drug or multidrug medical therapy (4 to 10 points higher).29 This is probably because nonablative and nonresective treatments do not as effectively de-obstruct the bladder outlet.

There was no evidence of variation in the degree of effect across study sites or geographies. Additionally, efficacy in the TURP control group as reflected by symptom score and uroflow improvements were large and consistent with expectations, adding overall validity to the trial outcomes. TURP resection time, PSA reduction and resected weight were lower than in previous reports but this did not appear to negatively impact TURP efficacy. Longer followup of the TURP arm would determine whether removing the right tissue vs maximizing the amount of tissue removed affects outcome durability."

Conclusions

"This study provides what is to our knowledge the first randomized comparison of Aquablation of the prostate and TURP in men with LUTS due to BPH. Each group achieved significant symptom relief compared to baseline with similar rates of Clavien-Dindo 2 or greater complications. The risk of anejaculation was lower with Aquablation. Larger prostates (50 to 80 ml) demonstrated a more pronounced safety and efficacy benefit. These results suggest that Aquablation of the prostate may be an effective and safe approach to the surgical management of LUTS secondary to BPH with a substantially lower rate of ejaculatory dysfunction compared to TURP. Longer followup would help assess the clinical value of Aquablation."

What Did I Learned From Reading This Paper?

1) Greatest Feature of Aquablation The most striking feature is the 2% retrograde ejaculation for the group of patients that had 50-80 cc prostrates as opposed to 10% for the entired group that had 30-80 cc prostrates. If the PIs of the WATER trial can figure out how the 50-80 cc had done it and then apply to all patients, it would be a significant contribution to BPH patient community.

2) Heated vs Heatless Haemostasis 

"....anejaculation was less common after Aquablation than after TURP (10% vs 36%). The anejaculation rate after Aquablation was somewhat lower when posttreatment cautery was avoided (7% vs 16%)."

The Heatless Haemostasis reduces the retrograde ejaculation rate by more than a factor of two. The 10% RE rate, I believe was from both heated and heatless haemostasis. I had seen someone reported  6.7%RE for aquablation. It could be because the surgeon used heatless haemostasis.

Regardless, more research needs to be done to understand the heatless benefits and see if it contributed  to or  what it has to do with the 2% RE. When the PIs find out what had happened, then make it into a guideline to be followed by all urologists who perform aquablation.

3) Complications

For given functional outcomes, safety is most important. We already know for functional outcomes, aquablation is slightly better than TURP. Table 2 listed all the complications categories. For CD2 and greater events, Aqua and TURP are similar. However, for CD1 event that Aqua is better (33.6% vs 45%). I read it somewhere that this was primarily driven by Aqua having a much better outcome in ejaculation. If we take ejaculation out, then the remaining CD1 events end points are about the same in both arms. In other words, Aqua and TURP have about the same amounts of complications, but for Aqua gives us less than 10% RE.

4) Incontinence

Incontinence is a severe complication for HoLEP. HoLEP reciepients may have to wear urine pads for months. Thus, I am concerned about Incontinennce.

In Figure 3 Safety outcome  CD1P, it included incontinence, erectile dysfunction and ejaculatory dysfunction. So there is no information on incontinence alone.

The Aqua's  ISI score is 1.2 point better than TURP, but the ISI score is 0-12 points (the lower the better). Improvement of 1.2 points is not a significant change. But other trials which had fewer patients reported that there were no incontinence. So jury is still out for incontinence.

5) Volume of Tissue removed

Aquablation removed significantly less tissue (25-30% less) than TURP, but yet has comparable  IPSS, Qmax and PVR. Less tissue removed may have  contributed to the <10% RE. Perhaps, TURP removed tissues that do not contribute to functional outcomes.

6) Hospital Stay and Catheter Time

I am surprised that both Aqua and TURP have an average of 1.4 days of hospital stay and 1 day catheter time. This is at odd with our understanding that TURP normally requires longer hospital stay and catheter time. If this is so, then the length of hospital stay and catheter time is comparable to HoLEP that is HOLEP does not have an advantage in this category. 

We are learning more and more about the pros and cons, advantages and disadvantages of Aquablation using the water jet technology.

I have spent a lot of time to prepare the latest and important information contained in this paper for the community.

This is the paper which claims aquablation has 2% retrograde ejaculation (anejaculation) for prostrate size >50 g(cc). It contains important info about aquablation, which is how well aquablation works for men who have prostrates of 50-80 cc by examining the recorded results contained in the latest international WATER trial. It examines Aquablation performance by dividing the patients into various subgroups: prostrate size <50cc or >50cc; age <65 or  >65; Qmax baseline or <9cc; with and without middle lobe, and middle lob obstruction (mild, moderate or severe); IPSS baseline <20 or >20;  PVR<100, PVR>100cc.

IPSS baseline  <20  means with moderate disease and Qmax <9 cc means prostatic urethra is severely obstructed, PVR>100cc means poor baseline bladder function.

We shall see 50-80 cc is a range of prostrate, in some subgroups  TURP's improvement in IPSS is not great. On the contrary, for Aqua, it maintains an IPSS improvement of 17 points in all the subgroups. The Aqua's IPSS improvement does not seem to be dependent on age, Qmax, presence of middle lobe, and severe middle lob obstruction. On the contrary, TURP's IPSS improvement dropped significantly in those subgroups.

Not only Aqua has better functional outcomes, More importantly, it also has better safety than TURP.

What is surpassing is that ,within the Aqua arm, >50 cc prostrate has better safety than <50 cc prostrate. This is against common sense. What is most surprising is that retrograde rejection rate for <50 cc prostrate is 10 times more than <50 cc prostrate. Does this means that there could is an minor issue for <50 cc prostrate, for example the contour is not as precisely define as in >50 cc prostrate?

We now know for both safety, functional outcomes and ejaculation, aquablation is better than TURP.  However,  as patients, we also can choose other technologies so it is important for us to understand how well Aqua compares with other technologies such as GLL, HoLEP, Urolift, etc.

Also I will not be able to show the figures. So please refer to original paper. However, I could show the table after rearrangement.

The paper is

"Symptom relief and anejaculation after aquablation or transurethral resection of the prostate: subgroup analysis from a blinded randomized trial" by

Mark Plante  Peter Gilling  Neil Barber  Mohamed Bidair  Paul Anderson  Mark Sutton Tev Aho  Eugene Kramolowsky  Andrew Thomas  Barrett Cowan  Ronald P. Kaufman Jr Andrew Trainer  Andrew Arther  Gopal Badlani  Mihir Desai  Leo Doumanian  Alexis E. Te Mark DeGuenther  Claus Roehrborn, published in BJU International on June 2018 

The Purpose of This Study 

"Surgical approaches to the management of moderate-to-severe LUTS attributable to BPH include non-resective and resective techniques. While resective techniques generally have higher rates of symptom relief, they also carry a higher risk of adverse events. Moreover, it is generally accepted that the longer operating times associated with larger prostate volumes increase the risk of adverse events 1. Less well understood is the relationship between patient or procedure factors (e.g. prostate size, amount of tissue removed) and symptom reduction efficacy and adverse effects."

(Note: it does not claim that aquablation has less operating time even if Aqua's water jet resecting time is 4 minutes for almost all prostrate sizes.)

"We conducted prespecified and post hoc exploratory subgroup analyses from a double-blind, multicentre prospective randomized controlled trial that compared transurethral resection of the prostate (TURP) using either standard electrocautery vs surgery using robotic waterjet (aquablation) to determine whether certain baseline factors predicted more marked responses after aquablation as compared with TURP. " "We tested this hypothesis through pre-planned and exploratory subgroup analyses from the WATER study. "

"Pre-planned subgroups of interest specifically focused on men with moderate disease (baseline IPSS <20), men in the Medicare population (aged =65 years), and men with large prostates." "Exploratory analyses were conducted to examine other aspects of challenging anatomy or pathophysiology (enlarged middle lobe, degree of median lobe obstruction and impaired bladder function related to chronic obstruction)."

"The TURP procedures were performed according to the standard practice with monopolar or bipolar electrocautery loops and isosmolar irrigation fluid. Aquablation was performed using the AquaBeam® System. ...After aquablation was complete, haemostasis was achieved using either focal, non-resective electrocautery (first 40% of enrolment) or low-pressure tamponade with a Foley balloon catheter in the prostatic fossa (last 60% of enrolment) 6. Postoperatively, all participants received continuous bladder irrigation."

(Note: both heated and heatless haemostasis were used.)

End Points For This Study 

"The primary efficacy endpoint was reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien–Dindo persistent grade 1 or grade =2 surgical complications."

General Results

"For men with larger prostates (50–80 g), the mean IPSS reduction was four points greater after aquablation than after TURP , a larger difference than the overall result (1.8 points). Similarly, the primary safety endpoint difference (20% vs 46% [26% difference]) was greater for men with large prostate compared with the overall result (26% vs 42% [16% difference]). 

Postoperative anejaculation was also less common after aquablation compared with TURP in sexually active men with large prostates (2% vs 41%) vs the overall results (10% vs 36%). "For anejaculation rates, only participants who were sexually active at baseline were included."

(Note: for larger grand, TURP has more anejaculation cases. Larger grand takes a longer time to operate. This may suggest heat is the cause for increased anejaculation.)

Exploratory analysis showed larger IPSS changes after aquablation in men with enlarged middle lobes, men with severe middle lobe obstruction, men with a low baseline maximum urinary flow rate, and men with elevated (>100) post-void residual urine volume."

(Note: This is new information.)

Detailed Results

Safety

Comparing with TURP, "For pre-planned subgroups, the largest difference in the primary safety endpoint rate was in men with prostate size >50 mL (20% aquablation vs 46% TURP  [Table 2 and Fig. 4]). The proportion of men experiencing Clavien– Dindo grade =2 complications was numerically but not statistically lower in men overall, with minor differences across pre-planned subgroups. In exploratory analyses, the primary safety endpoint was numerically lower in all subgroups, with statistical significance seen for men with middle lobes and men with low baseline Qmax. Amongst sexually active men, anejaculation rates were lower with aquablation in all subgroups, especially in men with large prostates (2% vs 41%).

Table 2 Primary safety endpoint event rates by treatment and subgroups.

N with event/N (rate in %)

                        Aquablation    TURP    

Baseline IPSS

<20                 6/36 (17)    9/23 (39)

=20                 24/80 (30)    18/42 (43)    

Age

<65 years    10/50 (20)    11/27 (41)

>65 years    20/66 (30)    16/38 (42)    

Prostate volume

<50 mL    17/52 (33)    11/30 (37)    

=50 mL    13/64 (20)    16/35 (46)    

Primary safety endpoint was defined as Clavien–Dindo grade =2 and persistent Clavien–Dindo grade 1 events. *Fisher's test.

(Note: Aqua has lower risk of complications than TURP in all subgroups. Men with Lower IPSS , young men and men with larger prostrate has lower risk of complications.)

Fig 1 showed IPSS improvement. At month 6, Aqua=17, TURP =14.

Fig. 1 Change in IPSS score by time, treatment and preplanned subgroups. Solid blue = Aquablation; dotted red = TURP. In this and subsequent figures, numbers show P-values for 6-month change score comparisons across treatments and inset plots show voiding and storage subscore changes from baseline with 6-month change score P-values.

Fig. 2 Change in IPSS score by time, treatment and preplanned subgroups. Solid blue = Aquablation; dotted red = TURP. (The subgroups are age <65, >65, IPSS baseline <20, >20, prostrate volume <50,  >50)

Fig. 3 Change in IPSS score by time, treatment and exploratory subgroups. (A) presence of middle or lateral lobe and degree of middle lobe obstruction; (B) baseline Qmax > or < median value of 9 cc/s, bladder neck obstruction and baseline PVR < or >100 cc. Solid blue = Aquablation; dotted red = TURP. (The subgroups are: lateral lobe, middle lobe, middle lobe obstruction (none, mild, moderate and severe))

Please refer to figures 2-3 of the original article. My interpretations of the results given in figures 2-3 are given below.

IPSS

Aqua and TURP both did not do so well for IPSS baseline  <20 (the improvement was about 11 points for Aqua and 8 points for TURP). But both did very well for IP SS BL>20 (improvement is about 19 points for both). IPSS baseline  <20  means with moderate disease.

Other than that Aqua's IPSS improvement seems to be independent of age ( improvement about 17 points, whereas TURP was slightly worse ) and more or less independent of size of prostate (30-80 cc). For <50cc and >50 cc, Aqua's improvement was 16 and 17 points (the usual value)  respectively. TURP for >50 cc did poorly and the improvement was only 13. Thus for >50 cc  Aqua is better than TURP by 4 points, but this is because Aqua had maintained its usual improvement of about 17 points, but TURP had dropped its value to 13.

Middle Lobe, Lateral Lobe, Middle Lobe Obstruction 

Aqua and TURP have about the same improvement for men with only lateral lobe enlargement  (i.emno middle lobe enlargement), or have mild or moderate middle lobe obstruction. In these cases, the IPSS improvement for Aqua is the usual 17 points and is about the same for TURP.

However, when there is a middle lobe or there is (mild, moderate or severe middle) lobe obstruction (indicating obstructive symptoms), Aqua improvement is 16 ( for middle lobe) and  18 points (for obstruction) respectively (17 is the usual value), whereas TURP does poorly in the later two cases, in both cases the improvement was only about 11 points each.

Qmax

Again Aqua is more or less independent of Qmax. For baseline Qmax, the improvement was 16 points (about the same for TURP) whereas  for <9 cc Qmax (severely constricted urethra) the improvement is 18 points. But TURP did portly for <9 cc and the improvement was only 14 points.

Bladder Neck Obstruction 

Aqua does not seems to be affected by BNO. With BNO, the improvement is 17 points, same value for TURP.

PVR

When PVR<100cc, improvement for Aqua and TURP is about 16 points. When the symptom is serious I.e PVR>100cc (indicating poor baseline bladder function), Aqua's improvement was the usual 17 points whereas TURP was 13 points.

Summing it up, for all the above cases, Aqua's IPSS improvement was between 16-18, whereas TURP dropped its IPSS points significantly when the prostrate was >50cc , when Qmax was <9cc, when there was middle lobe or severe middle lobe obstruction and when there was large PVR.

"The 6-month changes in PSA levels were similar across groups, with no statistically significant differences across treatment arms within individual subgroup levels."

Discussion

"IPSS subscore improvements appeared to correlate with abnormal baseline physiology, with improvements in voiding subscores in groups with large middle lobes and high degrees of middle lobe obstruction (indicating obstructive symptoms), and improvements in storage subscores in men with no baseline bladder neck obstruction and high baseline PVR values (indicating poor baseline bladder function). Men with low baseline flow rates had superior improvements in both voiding and storage subscores. These findings suggest that robotically executed, physiologically relevant prostate tissue removal may be more effective and consistent in removing obstructing tissue and improving bladder function, especially in the setting of more complex anatomy, compared with TURP, a procedure that, with large prostates, requires substantial experience and expertise as well as longer operating times. For men without bladder neck obstruction, aquablation showed superior IPSS changes. This may be explained by the previously stated rationale that aquablation resects a consistent opening even in men in whom the obstruction is not obvious."

Retrograde Ejaculation

"Retrograde ejaculation after TURP, a common finding (63% in one key study 8), is probably attributable to heat-related damage to the ejaculatory ducts. The reduced rate of anejaculation in the present study is probably attributable to enhanced resection precision through image guidance and robotic execution, which avoids damage to the ejaculatory ducts around the verumontanum and lack of heat-related damage."

(Note: it claims Aqua resection is precise.)

"The relatively low observed anejaculation rate in the present study in the TURP group compared with other studies is probably attributable to adjudication of this endpoint as anejaculation (after evaluation by a clinical events committee) as opposed to patient reports of reduced ejaculation."

Comparing with TURP, "Lower rates of postoperative anejaculation after aquablation were significant in men with large prostates (2% vs 41%) and statistically lower rates were seen in most subgroups (pre-planned and exploratory analyses). Clavien–Dindo grade =2 complications trended in favour of aquablation with larger prostates (19% vs 29%), although this difference did not reach statistical significance (Table 3)."

Table 3 Anejaculation (at risk denominator) by treatment and subgroups.

Format: N with event/N  (rate on %)

                     Aquablation     TURP    

Baseline IPSS

<20                2/30 (7)    7/16 (44)    

=20              6/48 (12)    9/29 (31)    

Age

<65 years    3/37 (8)    8/24 (33)    

>65 years    5/41 (12)    8/21 (38)    

Prostate volume

<50 mL    7/34 (21)    7/23 (30)    

=50 mL    1/44 (2)           9/22 (41)

(Note:  there is a factor of 10 difference between prostrate >50 cc and <50 cc. It is hard to understand why. Perhaps, for smaller prostrate, the aquabeam contour is not as accurate as in larger prostrate. Also older men has a higher chance to get RE.)

Discussion 

"Subgroup analyses from this randomized trial lend support to a shift in the treatment of BPH, using image guidance and robotic execution to improve targeting and precision of tissue removal, potentially producing superior symptom score improvements while avoiding structures whose heat-related ‘collateral damage’ commonly causes retrograde ejaculation."

"Strengths of the present study include its prospective, multicentre, international, blinded design, as well as observed TURP IPSS changes in the same range as those reported in previous similar studies 9. Our findings are especially noteworthy, given that the trial involved surgeons with substantial TURP expertise but no experience with aquablation in 14 of 17 sites. "

Caution 

"The findings of the present study should, however, be interpreted with caution as, except for prostate size, age and baseline IPSS, most analyses were exploratory (not pre-planned), sample sizes were limited, and the follow-up was 6 months. The relative symptom relief advantage of aquablation could not be demonstrated in men with smaller prostates, in which case TURP may more easily and consistently remove offending tissue, yielding similar results to those achieved with larger prostates."

Conclusion 

"In conclusion, the prespecified subgroup analysis from a blinded randomized clinical trial showed that, in men with larger (>50 g) prostates, resection using aquablation provided higher symptom score reduction and a reduced rate of postoperative complications (especially anejaculation) compared with TURP. In men with larger prostates, the rate of Clavien–Dindo grade =2 complications trended in favour of aquablation (19% vs 29%). The advantages of standardized, robotically executed BPH surgery are confirmed as the treatment complexity increases." 

we know by now the longer the device is inside the prostrate, it increases substantially the chance for more complications. We also know that for prostrate 30-80 cc, the Aqua resecting time is about 4 min. Can we take advantage of that?

So so my question is can the contour planning be executed with the rectal ultrasound in place but without the device being inserted inside the prostrate. This may reduce the time the device is in the prostrate.

another useful piece of info to the patients will be how the contour is decided. There should be a rigid guideline, for example X mm above the verumontanum and Y mm away from other important anatomical landmarks. OR if there are tradeoffs for different kind of results. Since Aqua is robotic, all the landmarks should be easily marked and the contour can be programmed without human intervention.

More:

On addition to anejaculation (nothing comes out) another useful parameter to give to the patients is "perfect ejaculation" I.e there is no change in ejaculation before and after aquablation.