Dispersion of steam ablation zone of the prostate with convective water vapor energy ablation. (Courtesy of Boston Scientific, Maple Grove, MN, USA)
In a multicenter, randomized, controlled study, 197 men were enrolled and randomized in a 2:1 ratio to treatment with the Rezūm System or control [42]. The primary efficacy end point was a change in AUASI of 50% for the active treatment arm versus 20% for the controls (11.4 points vs 4.2 points, p < 0.0001). In the vapor arm Qmax increased by 67% from 9.9 ml/sec to 16.1 ml/sec while Qmax in the control arm increased from 10.4 ml/sec to 10.8 ml/sec (P < 0.0001) at the 3-month mark. These encouraging outcomes were sustained throughout the 1-year follow-up.
The adverse event profile was favorable with events documented to be mild to moderate and quickly resolved. In contrast to most of the novel minimally invasive techniques, all critical prostatic zones including the middle lobe were successful treated. Preservation of erectile and ejaculatory function was demonstrated by no change in mean IIEF score and a significant improvement in MSHQ-EjD at 1 year. The 2-year results confirmed durability of the positive clinical outcome after convective water vapor energy ablation. Thus, this novel technology is able to provide rapid and meaningful improvement of LUTS without significantly impacting sexual function. The long-term durability requires demonstration.
Prostatic urethral lift (UroLift® System, NeoTract, Pleasanton, CA) is a non-ablative approach to treating LUTS/BPH. This trans-prostatic tissue compression consists of a nitinol capsular anchor connected to a stainless steel urethral endpiece by a monofilament (PET) suture tensioned in situ which mechanically opens the prostate and relieves obstruction without ablation or resection. During trans-urethral deployment, a handheld delivery device is inserted through a cystoscope. The device deploys a spring-actuated implant that compresses the lumen of the prostatic urethra towards the prostatic capsule, which when repeated sequentially opens the urethra thus relieving the obstruction.
The UroLift System has published peer-reviewed 5-year data on its endoscopic device designed to treat men with bladder outlet obstruction.
Only a small number of studies comparing PUL versus TURP (BPH6 Study) have been published [43, 44]. The data indicate that a lower proportion of individuals in the PUL group responded to treatment at 12 months of follow-up compared to TURP as measured by the I-PSS reduction goal of ≥30% (73% versus 91%; P = 0.05). At 24 months of follow-up, the mean difference between PUL and TURP was 6.1 points (CI: 2.2, 10.0) favoring TURP; however, changes in I-PSS-QoL were similar between groups at all follow-up intervals. Additionally, Qmax was significantly lower in participants allocated to PUL at all follow-up intervals, while changes in prostate volume were not reported. The need for reoperation due to symptom recurrence did not differ between groups over the 2-year study (RR: 2.4; CI: 0.5, 11.1). Although the incidence of serious and nonserious harms related to treatment, need for reoperation, and incontinence was similar between the PUL and TURP groups, reported incidence for incontinence for TURP was reported at 17.1% compared to 1.7% for PUL (CI: 0.3–18.0). In reviewing this study, one may note that “incontinence” was poorly defined as it relates to the unusually high incidence reported in the TURP arm. Additionally, one should note that the quality of evidence for nonserious harms related to the procedure is rated low while that for incontinence, need for reoperation, and serious harms related to treatment is rated very low.
Regarding PUL compared with sham (L.I.F.T Study), both mean change from baseline I-PSS (MD: −5.2; CI: −7.45, −2.95) and improvements in I-PSS-QoL (MD: 1.2; CI: 1.7, −0.7) favored PUL. Additionally, mean change in Qmax at 3 months was higher for those who underwent the PUL procedure (4.3 mL/s) compared to the sham control (2.0 mL/s), P = 0.005. Of the participants randomized to PUL, 5-year follow-up data slightly decreases in mean I-PSS and QoL scores; however, both remained significantly improved from baseline. Only one treatment-related serious adverse event was reported during the double-blind phase of the study. In the short term, there were significantly more treatment-related harms, serious and nonserious, in the PUL group compared to sham (RR: 2.7; CI: 1.8, 3.9). Events included dysuria, hematuria, pelvic pain/discomfort, urgency, bladder spasm, UTI, and retention [45].
PUL provides durable relief of LUTS through 5 years with minimal side effects. Five-year follow-up data revealed only minimal deterioration of benefit, with significant improvement to baseline maintained. Reoperation due to symptom recurrence at 5 years was reported for 19 of 140 participants with 6 receiving additional PUL implants and 13 undergoing TURP or laser procedures. Removal of encrusted implants was required in 10 participants while 3 non-encrusted implants exposed to the bladder were removed prophylactically. Additionally, 15 participants were taking an alpha blocker or 5-alpha reductase inhibitor at 5 years. Given that approximately one third of the initial study population experienced unsatisfactory results necessitating further treatment, patients selecting PUL should be informed that this is a relatively new intervention for LUTS/BPH with uncertainties in long-term durability, though such uncontrolled data are available.
The universal applicability of PUL is limited by current contraindications including prostate volume >80 cc and the presence of an obstructive middle lobe. Additional studies are underway to help more fully elucidate the limitations but are not available for review. As with other technologies included in this review the long-term durability remains to be seen.
Transurethral needle ablation (TUNA) utilized radiofrequency energy to heat the prostatic tissue to stimulate tissue necrosis of the adenomatous tissue while preserving urethral mucosa. The energy is applied by inserting two needles via a cystoscopic device into the lateral lobes of the prostate. Depending of the volume characteristics of the gland itself, a single or multiple treatment cycles may be required. In the 2018 AUA BPH Clinical Guidelines, this technology was not recommended [46].
Transurethral microwave thermotherapy (TUMT) utilized microwave energy via a urethral catheter with mounted microwave antennae to heat the prostatic tissue to temperatures ranging from 45° to 70 °C, thereby stimulating tissue necrosis. Many of these systems have attempted different strategies to protect the urethral tissue, commonly utilizing a cold-water channel along the outer circumference of the catheter. Microwave technology has been developed by multiple manufacturers, and as a result, a significant amount of variability in the technology exists.
Success of TUMT relies heavily on patient selection, as variations in prostatic anatomy (e.g., oversized gland, median lobe, etc.) can distort the energy transmission. Furthermore, the microwave energy has the potential to interfere with other implanted devices such as pacemakers, defibrillators, penile prostheses and metallic joint implants.
Hoffman and colleagues performed a Cochrane review of six trials comparing TUMT and TURP; the mean improvement in AUA-SI was 65% for TUMT compared to 77% for TURP [47]. Similarly, TURP improved urine flow rates by an average of +119%, while TUMT improved by an average of 77%. Thus, TUMT appears to provide inferior improvement in patients’ voiding yet holds the benefit of being performed as an office-based procedure requiring only local anesthesia. Thus, the AUA Guidelines Committee rendered the recommendation that TUMT be offered, with the caveat that the risk of reoperation be discussed in detail with the patient.
Transurethral Incision of Prostate (TUIP)
The concept of incising the prostate at the level of the bladder neck to treat symptoms of BPH/LUTS was first presented by Guthrie in 1834, suggesting that disruption of the bladder neck to allow the bladder to empty without restraint. Ideally a unilateral or bilateral incision is made at the 5 and/or 7 o’clock position at the level of the bladder neck. The ideal situation would be a small but obstructing gland, <30 grams. The benefit of TUIP is preservation of antegrade ejaculation. Orandi and colleagues suggested that avoidance of the bladder neck entirely is the best means to preserve ejaculatory function [48]. Orandi also wrote that the median lobe does not represent a contraindication to TUIP, but that larger glands may achieve reduced benefit [49].
Prostatic Ablative Therapy
Transurethral resection of the prostate (TURP) utilizes electrocautery energy passed across a thin filament loop. With the current activated, the loop is passed through the adenomatous prostatic tissue from the level of the bladder neck to the verumontanum. The activated loop cauterizes the blood vessels feeding the prostatic tissue creating chips of resected tissue. The resection is continued circumferentially along the bladder neck prior to targeting the lateral prostatic lobes. One lobe is completely resected prior to performing an identical procedure on the contralateral lobe. The typical anatomic landmarks utilized to establish the field of resection include the bladder neck proximally, verumontanum distally and the prostatic capsule to establish the appropriate depth. Care is taken while resecting at the level of the bladder neck as to not extend the loop into the bladder lumen to avoid inadvertent injury to the ureteric orifices. At the conclusion of the resection, the produced prostatic chips are then evacuated from the bladder prior to placing a large caliber urethral catheter. The energy generator employed for the procedure may be of either monopolar or bipolar design.
Monopolar
The use of TURP has been in practice since the early twentieth century. For many years monopolar was the sole energy source option. The current supplied by a monopolar resectoscope is carried from the resecting loop to the prostatic tissue and returned to a grounding previously placed on a patient. In order to ensure effective and efficient conductivity of this energy, a nonionic, hypo-osmolar irrigation solution must be employed. Typical solutions include sterile water, sorbitol and glycine. Given the extensive vascularity of the prostatic resection bed, this requirement risks substantial absorption of this hypo-osmolar fluid into the circulation. Excessive absorption can lead to a danger of dilutional hyponatremia, a condition later referred to as post-TURP syndrome. As such, it is recommended that postoperative serum electrolyte assessment be carried out in the postoperative care unit. In an effort to decrease the risk of post-TURP syndrome, resection times should be maintained less than 90 minutes [50].
Though the original outcomes research for monopolar TURP preceded many of the validated questionnaires for BPH-associated LUTS, TURP has long been believed to be an effective and durable BPH intervention. While post-TURP syndrome represents the most worrisome complication included in the adverse event profile for monopolar TURP, thankfully, it is uncommon. The most commonly cited complications of TURP include UTI, ejaculatory dysfunction, urethral stricture formation and urinary incontinence. Issa and colleagues (2008) found that up to 2.5% of individuals will require reoperation [51].
Bipolar
The development of a bipolar working element allowed for the containment of the electrocautery current within the resecting loop rather than traveling through the patient to a previously placed grounding pad. This allows for the current to be maintained at the site of resection. As a result of this advancement, the use of hypo-osmolar irrigation solution was no longer required, thus allowing the surgeon to utilize iso-osmolar solutions (i.e., normal saline) reducing the risk of post-TURP syndrome while also allowing for improved hemostasis. The increased efficiency of both resection and coagulation led to decreased operative times [52]. When comparing bipolar with the established monopolar energy system, Issa and colleagues looked at 10 years’ worth of data noting similar outcomes in improvement of urinary flow rate, reduction of PVR, and improved AUA-SI and QoL scores [51, 52]. Recent metanalyses by Cornu and colleagues and Omar and colleagues reported similar results [53, 54].
Mamoulakis et al. did report, however, that bipolar TURP was associated with significantly less adverse events compared to monopolar TURP (15.5% vs. 28.6%, P < 0.01) [55]. Of the cited differences, perioperative bleeding appeared to be of significant importance (bleeding, transfusion, duration of indwelling catheter, need for continuous bladder irrigation, post-TURP syndrome). Similar to monopolar TURP, perioperative adverse events include TUI, urethral stricture formation, urinary incontinence, and need for repeat procedure.
Transurethral vaporization of the prostate (TUVP) represents a modification on the TURP platform. Using either monopolar or bipolar energy (bipolar far most commonly utilized), the current is applied to the prostatic tissue by an electrode to vaporize the prostatic tissue. By concentrating the tissue density, this design aims to increase the efficiency of tissue ablation while maintaining better visualization and providing improved hemostasis. The electrode is available in a variety of shapes; most commonly used include the button, rollerball, and the grooved roller. TUVP has gained popularity as a teaching tool, with many believing it provides an ideally controlled setting for the instruction of future urologists.
Over 20 RCTs have been performed evaluating TUVP versus TURP (both monopolar and bipolar) [56–80] with the majority indicating no significant difference in the overall effectiveness, need for reoperation, incidence of major complication, or need for blood transfusion.
Photoselective vaporization of the prostate (PVP) utilizes laser energy at a wavelength of 532 nm to vaporize the prostatic tissue. This is achieved by selective absorption of the laser energy by hemoglobin resulting in tissue ablation, leaving behind a thin layer of coagulation for hemostasis. Using a technique similar to TURP, a channel is created within the prostatic urethral allowing the bladder to expel urine with minimal outlet resistance. This technique was popularized using an 80 W energy generator, with subsequent advances leading to the 120 W and most recently 180 W generators available for more efficient tissue vaporization. The GOLIATH study [81–83] compared 180 W PVP with traditional TURP in a non-inferiority design. Though the investigators were not able to meet the non-inferiority criteria of a 3-point difference in IPSS, they did show that PVP was similar to TURP in adverse event incidence, need for blood transfusion rates, decrease in PVR, decrease in prostate volume (by both TRUS and PSA), and need for reoperation.
Many experts believe that PVP is best suited for older men with more complex medical comorbidity indices, those with long-term anticoagulation therapy and small- to medium-sized prostates. Attributed to the thin layer of coagulation effect of the PVP, many believe VP holds a reduced risk of bleeding complications. Furthermore, PVP has frequently been utilized as ambulatory procedure, thus providing significant cost savings on hospitalization as shown by van Melick et al. [65, 66].
Holmium laser enucleation of the prostate (HoLEP) utilizes energy via a holmium: yttrium-aluminum-garnet (Ho:YAG) laser with a wavelength of 2140 nm. The energy is absorbed by the irrigation fluid at the tip of the fiber creating a vaporization bubble allowing for destruction of the prostatic tissue with minimal deep tissue penetration [84]. The prostate is enucleated along its surgical capsule with the resultant tissue morcellated using a separate device. In comparison with TURP, HoLEP has demonstrated similarly improved voiding symptoms, shorter catheter indwell time, and shorter hospitalization, with similarly uncommon adverse events. TURP did have the benefit of shorter operative times [85–91].
A distinct benefit of HoLEP is its applicability to large prostate glands. In a 2008 trial by Kuntz and colleagues, HoLEP was compared to open prostatectomy for men with gland volume >100 mL. The HoLEP group had significantly shorter hospital stays, catheter indwell times, and perioperative bleeding complications while maintaining similar improvement in both IPSS and urine flow rates [92].
Particularly in Europe, HoLEP has gained significant popularity. However, a perceived steep learning curve has limited its utilization in the USA.
Holmium laser ablation of the prostate (HoLAP) utilizes holmium energy with its vaporization bubble to ablate the prostatic adenomatous tissue. While the limited depth of penetration is considered a safety benefit of holmium-based laser systems, it also limits the efficiency of tissue destruction. As such the use of HoLAP, which incorporates a technique similar to TUVP, has fallen out of favor.
Simple prostatectomy/robotic approaches consist of enucleating the prostatic tissue with its capsule. Historically this has been achieved via an open surgical approach; however with the establishment of laparoscopy and subsequently robotically assisted approaches, simple prostatectomy has also evolved. Most commonly, simple prostatectomy is reserved for individuals with large prostates that would render more minimally invasive transurethral techniques difficult. Both open and laparoscopic/robotic approaches have been shown to greatly improve IPSS and urine flow rates with excellent long-term durability [93–96].
Limitations of simple prostatectomy of course include the requirement for major surgery and postoperative hospital admission. Significant perioperative blood loss represents the most commonly implicated complication, though development of urethral stricture disease (particularly bladder neck contracture) deserves significant consideration.
Alternative Drainage in Special Situations
Clean Intermittent Catheterization (CIC)
Clean intermittent catheterization (CIC) represents a means of bypassing an obstructed outlet. An inserted urethral catheter serves as a temporary conduit for bladder drainage. Clean intermittent catheterization (CIC) represents a means of bypassing an obstructed outlet. An inserted urethral catheter serves as a temporary conduit for bladder drainage and is useful for individuals who suffer from weak detrusor contractility in addition to the outlet obstruction. Though this approach does not address the underlying pathology, maintaining low urine storage pressure prevents deterioration of the upper tracts.
Intraprostatic Urethral Stent
Positioning of temporary indwelling prostatic stent. (Spanner®) (Courtesy of SRS Medical Billerica, MA, USA)
The Urolume™ , constructed of a nickel superalloy wire mesh, was initially developed for use in men with bulbar urethral strictures and was quickly used in individuals with BPH gaining significant popularity; it has, however, been taken off the market due to stent encrustation and migration (complications common to most intraprostatic endoprostheses) [98–100]. Other prostatic/urethral stents have utilized a variety of materials: nitinol, polyurethane, polyglycolic acid, and stainless steel [101]. The advantage of this approach is that these intraprostatic devices can frequently be placed as an office-based procedure without general anesthetic, an attractive option for individuals who may be poor surgical candidates. Most recently, the Allium™ intraprostatic stent has been developed. The Allium™ is a polymer-covered nitinol-based product, triangular in shape in an effort to prevent encrustation. Denmeade and colleagues in 2011 demonstrated significant improvements in both IPSS and urine flow rates [102].
Surgery in Special Populations
What to Do with Medically Complicated Patients and Those on Anticoagulants
Multiple studies have shown that the need for a blood transfusion (either peri- or postoperatively) was significantly less likely with HoLEP as compared to TURP (RR: 0.20; CI: 0.08, 0.47).
In addition, studies of holmium laser prostate surgery in patients maintained on anticoagulation therapy at time of surgery have supported a relatively low transfusion rate. In a 2013 retrospective review on a series of 125 patients treated with HoLEP (52 patients were on antithrombotic therapy at the time of surgery and 73 patients were not), only 4 men (7.7%) in the antithrombotic group required a blood transfusion compared to none in the control group [103]. A similar 2016 study compared 116 patients who required anticoagulation/antiplatelet therapy at the time of HoLEP to 1558 patients who did not. Other than a slightly increased duration of bladder irrigation and hospital stay, the use of anticoagulation/antiplatelet therapy did not adversely affect outcomes [104]. Lastly, a 2017 meta-analysis of patients on therapeutic anticoagulation/antiplatelet therapy when undergoing HoLEP supported that this approach can be performed safely on these patients but stressed that there are limited data surrounding the class of direct oral anticoagulants and safety [105].
PVP is performed using the KTP laser, which has a wavelength of 532 nm and a chromophore of hemoglobin. The depth of penetration with PVP is 0.8 mm. Multiple studies have found that PVP is safe and effective for patients who continue their anticoagulant/antiplatelet therapy, with negligible transfusion rates. However, surgeons should be aware that longer catheterization and irrigation with an increased rate of complications have been reported, and delayed bleeding is more pronounced in these patients [105–109]. A 2017 study confirmed these findings in 59 of 373 patients undergoing PVP. Overall, GreenLight PVP with the 180 W laser unit on patients therapeutic on heparin, warfarin, clopidogrel, dipyridamole, or new oral anticoagulant drugs revealed good safety outcomes [110, 111]. As expected, anticoagulated patients were older and had a higher American Society of Anesthesiologists (ASA) score than the control group, and although no patient required blood transfusion, there was a higher incidence of high-grade Clavien-Dindo events. Similar to other studies, the therapeutically anticoagulated group had a significantly longer length of hospital stay and duration of catheterization as compared to the controls.
Technologies in Development
Image-Guided Robot-Assisted Water-Jet Ablation of Prostate (Aquablation)
Aquablation is an emerging robotic, image-guided, highly engineered ablation of the prostate using a water jet, termed AquaBeam (Procept BioRobotics, Redwood Shores, CA) (See Chap. 17). The water jet is a high velocity hydrodissection tool that ablates prostatic parenchyma while sparing major blood vessels and the prostatic capsule. The urologist performs a surgical mapping of the prostate using transrectal ultrasound images. While still requiring general anesthesia and significant setup time and effort, the procedure is performed with remarkable efficiency.
In a single-arm multicenter pilot study, 21 men were enrolled and treated under general anesthesia. After 12 months, AUASI was reduced from 23.0 points at baseline to 6.8 points (P < 0.001). An increase from 8.7 ml/sec to 18.3 ml/sec in Qmax was demonstrated (P < 0.0001) No cases of urinary incontinence, erectile dysfunction or retrograde ejaculation were reported. Anatomical prostatic features like a prostate volume >100 cc, the presence of a large middle lobe and the anesthetic requirements are limitations to the technology [112]. Further randomized controlled trials are underway to evaluate efficacy, durability and safety of this approach.
Prostatic Arterial Embolization
Using digital subtraction angiography, the arterial anatomy and the appropriate prostatic arterial supply can be selectively embolized with various beads, gels, or non-spherical polyvinyl alcohol to infarct prostatic vessels and putatively reduce prostate volume, which may improve LUTS. Similar to all the options noted above, prostatic arterial embolization (PAE) can be performed in an outpatient setting. Technically, the most challenging part of PAE is to identify and catheterize the prostatic arteries. Prostatic arteries are very small arteries (1–2 mm in diameter) that may have variable origins from the collateral branches of the internal iliac artery. In contrast to uterine arteries, prostatic arteries lack pathognomonic findings and may be very difficult to identify with digital subtraction angiography before PAE.
Atherosclerosis, excessive tortuosity of the arterial supply and the presence of adverse collaterals are anatomical obstacles for the technical approach. Non-targeted embolization may lead to ischemic complications like transient ischemic proctitis, bladder ischemia, or seminal vesicle ischemia. Short-term complications, including urethral burning sensation, nausea and vomiting are common and have been coined the “post-PAE syndrome” [113]. The extended duration of the procedure with the requirement of fluoroscopy brings the risk of a relevant radiation exposure, which may result in skin irritation and even burns. Furthermore, contrast toxicity with the need for angiography is another adverse effect that must be acknowledged.
Currently PAE is performed under sedation by interventional radiologists or cardiologists, most without the benefit of research protocols, IRB approval, or proper trial design and measures. The selection of LUTS patients who will benefit from PAE still need to be defined. However, a recently published systematic review with meta-analysis and meta-regression on available data concluded that PAE should still be considered an experimental approach due to the reduced efficacy when compared with control groups. RCTs of good quality are still required to justify this technique on an elective indication (Clinicaltrials.gov: NCT02054013). It is important to stress that all of the MISTs noted above are able to specifically target the critical areas of BOO secondary to BPH. In contrast, PAE impacts the entire prostate without the option for focused and controlled action on obstruction. This may explain the higher clinical failure rate compared to reference methods like TURP and the commonly observed complications like acute urinary retention in almost 26% of cases [114].
TIND: Temporary Implantable Nitinol Device
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