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REVIEW ARTICLE
Year : 2023 | Volume
: 34
| Issue : 2 | Page : 55-63
Treatment of benign prostatic hyperplasia: Update and future
Tai-Hua Chiu1, Yi-Hsuan Wu2, Yung-Chin Lee3
1 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
3 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University; Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University; Kaohsiung Medical University, Kaohsiung, Taiwan
Correspondence Address:
Yung-Chin Lee
100, Shih-Chua 1st Road, Sanmin, Kaohsiung 807
Taiwan
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/UROS.UROS_134_22
Benign prostatic hyperplasia (BPH) is one of the widespread diseases affecting aging males globally. As prostatic cell proliferation, it clinically influences a great degree of bladder outlet obstruction and is characterized by bothersome lower urinary tract symptoms. Assessments and treatments should not only be conducted based on the prostate volume or condition, related symptoms and quality of life should be considered also. The present analysis focuses on the update of management for BPH, including pharmacotherapy and slightly invasive surgical options. Despite alpha-1 adrenoceptor antagonists, many other factors and even combination therapy were extensively studied. Regarding slightly invasive surgical treatments, including Aquablation, water vapor thermal therapy, prostatic artery embolization, prostatic urethral lift, and nitinol butterfly-like stent, we analyzed the latest findings of studies, as well as safety issues. Finally, we highlighted current guidelines for clinical practice and future direction for further investigation.
Keywords: Benign prostatic hyperplasia, lower urinary tract symptoms, minimally invasive surgical treatments
Benign prostatic hyperplasia (BPH), inducing prostatic enlargement and obstruction of the urethra, is a proliferation of glandular epithelial tissue, smooth muscle, and connective tissue at the transitional zone by histological research. There are several known risk factors such as race, genetics, alcohol, and metabolic syndrome, though aging is the most renowned.[1],[2],[3],[4] The natural course initiated in the fifth decade of life, attaining 80% by the age of 80 years.[5] The initial approach to BPH includes patient history, digital rectal exam, urinalysis, and prostate-specific antigen test. International prostate symptom score (IPSS), comprising 7 questions to break down the severity of lower urinary tract symptoms (LUTS), offers important information about micturition and guides treatment decisions. Furthermore, measurements of maximum urinary flow rate (Qmax) and postvoid residual (PVR) urine volume generally are presumed to be diagnostic tools.
As men age, mild-to-moderate LUTS resulting from BPH can be relieved by the first-line approach, behavioural, and lifestyle modification. Gradually, medication and surgical intervention may be implemented, or bothersome LUTS not only impact the quality of life (QoL) but causes adverse consequence when it advances, such as urinary tract infection (UTI), acute urine retention (AUR), and renal insufficiency. In recent years, innovative agents and combination treatments were studied thoroughly. For those who were fragile and unresponsive to medical treatments, minimally invasive surgical treatments became available and kept in advance. The current review sought to update the treatments for BPH and inform about the future direction.
Behavioral and Lifestyle ModificationThe basic step of BPH management is behavioral and lifestyle change. At the outpatient clinic, the physician enlightened patients about lowering the consumption of caffeine and alcohol, reducing liquid consumption, using the toilet before sleep, performing exercises to strengthen the pelvic floor muscles, doing bladder training, and preventing constipation. Besides, a healthy diet comprising vegetables and fruit instead of high protein or polyunsaturated fatty acid help to decrease the risk of BPH.[6],[7] Regular and thorough Physical activity indicated an inverse association with BPH and LUTS (odds ratio was 0.74).[8]
Pharmacological ManagementThough conservative treatment can be a choice for those who did not have significant LUTS, about 19% of patients were clinically advanced after a mean follow-up of 17 months of monitored waiting.[9] Alpha-1 adrenoceptor antagonists (α1-blockers) are the initial line of treatment for moderate-to-severe symptomatic BPH. They mitigated bladder outlet obstruction by inhibiting the effect of endogenous noradrenaline on smooth muscle cells in the prostate.[10] The efficacy and coexistence of different α1-blockers have been analyzed through direct or indirect comparisons,[11] and a recent study showed similar efficacy among different α1-blockers.[12] Objectively, urodynamic studies also demonstrated a considerable improvement of Qmax (2.27 ml/s, P < 0.0001), and mitigated bladder outlet obstruction index (BOOI) (−14.19, P < 0.0001) and detrusor pressure at Qmax (PdetQmax) (−11. 39 cm H2O, P < 0.0001).[13] Regarding well-documented adverse effects, such as vasodilatation-related dizziness and orthostatic hypotension, ejaculation disorder, or intra-operative floppy iris syndrome, counseling before treatments and adequate doses would help to maintain safety and medical compliance clinically.
Although α1-blockers were prevalently applied for LUTS, they cannot inhibit BPH advancement. Five-alpha-reductase inhibitors (5-ARIs), block the conversion of testosterone to dihydrotestosterone and lower the prostate volume.[14],[15] After long-term application, 5-ARIs enhanced IPSS clinically, lowered detQmax, and increase Qmax in urodynamic parameters.[16],[17] Furthermore, studies indicated that they mitigated the relative risk of AUR by 57%–68% and the requirement for surgery by 34%–55%.[18],[19],[20]
Antimuscarinics inhibit the activation of acetylcholine to muscarinic receptors and mediate voiding contractions, so they have been mostly applied for overactive bladder (OAB) patients. Treating BPH with antimuscarinics solely has been tested and demonstrated efficacy, particularly for those who were presumed nonobstructive BPH and OAB.[21],[22],[23] Kaplan et al. carried out a prospective study and revealed that treatment with antimuscarinics in men with BPH and refractory LUTS decreased urinary frequency and nocturia and greatly improved the American Urological Association (AUA) symptom scores and Qmax.[24] Furthermore, antimuscarinics are a supplementary choice for those experiencing α1-blockers with residual storage symptoms. Randomized controlled trials (RCTs) indicated a combination of antimuscarinics and α1-blockers was the rational therapy for BPH concomitant OAB because of its efficacy in reducing the frequency, urgency, and urinary incontinence and improving IPSS.[23],[25],[26],[27],[28] Although adverse effects of antimuscarinics and α1-blockers may be observed when receiving combination therapy, the AUR rate was low as 0.4%–1.1%.[23],[29]
Novel beta-3 agonists function on the beta-3 adrenoceptor which is a major role in mediating human detrusor relaxation. The agent can also be beneficial for male patients with LUTS, particularly in storage symptoms.[30] Monotherapy with Mirabegron 25 mg daily boosted the satisfactory rate and QoL for OAB male patients with or without BOO, though greatly decreased IPSS in patients without BOO.[31] Treatment with a combination of beta-3 agonists and α1-blockers worth assessing after antimuscarinics is proposed for men with refractory storage symptoms and experiencing α1-blockers monotherapy. Ichihara et al. investigated the addition of beta-3 agonists to α1-blockers greatly relieved daytime frequency, urgency, and IPSS despite open-labeled and short-term study design.[32] A recent MATCH trial discovered treatment with Tamsulosin 0.2 mg and mirabegron 50 mg was superior to a combination with tamsulosin and placebo in a stand of storage symptoms, voided volume each micturition, IPSS, and QoL in a high Asian population.[33] Another PLUS trial statistically demonstrated improvement in mean volume voided per micturition and urgency episodes per day rather than IPSS for a standard dose of Tamsulosin 0.4 mg plus mirabegron 50 mg.[34] In 2022, the European Association of Urology (EAU) guidelines for nonneurogenic male LUTS, patients with recurrent storage symptoms after treatment with α1-blockers monotherapy are suggested to use mirabegron. Although adverse effects of both drugs may be observed, drug-drug interactions did not induce clinically relevant changes in pulse rate and systolic blood pressure, remaining cardiovascular safety.[35]
Both LUTS and erectile dysfunction are common in aging males and epidemiologic studies have determined a correlation.[36] There are 4 theories indicating the link between LUTS and erectile dysfunction, the NOS/NO theory, the autonomic hyperactivity, and metabolic syndrome hypothesis, the Rho-kinase activation/endothelin pathway, and pelvic atherosclerosis.[37] Though the connection between LUTS and erectile dysfunction remains unclear, phosphodiesterase-5 (PDE-5) inhibitors have presented promising outcomes in preclinical and clinical studies.[36] Gacci et al. performed a meta-analysis with 3214 men and expressed that PDE-5 inhibitors alone substantially improved IPSS (−2.8; P < 0.0001) but not Qmax (−0.00; P = not significant) unlike placebo.[38] Another recent systemic research and meta-analysis revealed a comparable result.[39] However, an integrated analysis of tadalafil 5 mg statistically increased Qmax versus placebo (median 1.1 vs. 0.4 ml per s, P = 0.003).[40] Guo et al. directly contrasted PDE-5 inhibitors to Tamsulosin and there was no statistical difference in terms of IPSS, voiding subscores, storage subscores, QoL, Qmax, and PVR, signifying a similar therapeutic impact as Tamsulosin for BPH-related LUTS.[41] An updated systematic review and meta-analysis revealed the conforming results that the combination of alpha-blockers and PDE-5 inhibitors was superior to alpha-blockers solely in IPSS and Qmax.[42],[43],[44]
Minimally Invasive Surgical TreatmentMinimally invasive surgical treatments are innovative options for those who were unresponsive to medication or transurethral resection of the prostate (TURP) [Table 1].
AquablationAquablation, executed using the Aquabeam system (PROCEPT BioRobotics, Redwood City, CA, USA), is an innovative technology incorporating real-time image-based ultrasonic guidance and robotics with high-pressure (500–8000 pounds per square inch) saline jet for resection of prostate parenchymal tissue.[45]
The procedure of Aquablation was originally characterized by Farber et al. in 2015, and the effectiveness was further evaluated by many other authors with medium-term follow-up data expressed.[46],[47],[48],[49],[50] WATER I trial,[46],[47] conducted by Gilling et al., was the first double-blind, multicenter (across 17 different centers), prospective RCT, which included 181 patients who underwent Aquablation (n = 116) or TURP (n = 65) with prostate volume 30 and 80 mL. The mean resection time was shorter irrespective of prostate size in the Aquablation arm than in the TURP arm (4 min and 27 min, P < 0.001), while the total operative time was comparable in the 2 arms. Safety data at 3 months following the procedure revealed Aquablation to be noninferior to TURP. The Clavien–Dindo one events linked to retrograde ejaculation were observed in 24.6% of TURP patients and 6.9% of aquablation patients. The efficacy data at 6 months also revealed noninferiority in the aquablation arm, with similar improvement in IPSS (6.0 for aquablation and 6.7 for TURP). Besides, additional assessment of QoL, Qmax, and PVR also indicated comparable results in both groups. Urinary incontinence assessment, using self-reported incontinence severity index, was found to be improved following aquablation, unlike baseline. Besides, male sexual health questionnaire-ejaculatory dysfunction (EjD) scores were considerably low after TURP but stable in Aquablation groups 6 months postprocedure. At 5 years of follow-up data available in 2022,[49] IPSS advancements in the aquablation arm were 15.1 points and 13.2 points in the TURP. Improvements in Qmax were 125% and 89% than baseline in aquablation and TURP groups, respectively. Furthermore, the need for further BPH medication or surgery due to LUTS was 51% less in aquablation groups than in TURP groups.
The water II study sought to analyze the efficacy and safety of Aquablation in 101 patients with larger prostate (80–150 mL).[47] WATER II was also a prospective multicenter study, and as a single-arm study, it contrasted efficacy and safety with an objective performance criterion to assess noninferiority. The resection time was 8 min with a total operation time of 35 min. The 3-year follow-up data for WATER II are currently accessible.[48],[50] IPSS dropped from 23.2 at baseline to 6.5 at 36 months, and Qmax elevated by 9.8 mL/s. At 3 years, 94% of Aquablation-treated patients were BPH medication free and 97% of treated patients were free from surgical intervention due to LUTS. For an even larger prostate size, Helfand et al. analyzed the effectiveness and safety data in 34 patients with an average prostate volume of 209 mL (range 151–362 mL).[51] With a mean follow-up of 7 months, the IPSS declined from 19 to 7 points, and Qmax elevated from 7 to 19 mL/s.
As an athermal resection procedure, Aquablation lacks direct hemostasis for the resection bed after the intervention. A systematic analysis comparing different minimally invasive transurethral treatments for BPH indicated that hematuria or postoperative bleeding was 0.8%–26% in the studied literature and the need for reintervention or transfusion due to bleeding varied from 1.8% to 9%.[52] Hematuria-related complication after Aquablation without any cautery was found to be 10%.[53] The bleeding events had conformed to the concept of hemostasis with bladder neck cautery right after the procedure. Nonresective focal cautery at the bladder neck was an effective method for hemostasis after aquablation, with a transfusion rate of 0.8% and reintervention for a fulguration rate of 0.6% after the procedure.[54] In another analysis, with selective hemostasis on the prostate resection bed and on the bladder neck using bipolar cauterization, the rate of perioperative bleeding complication after aquablation was shown to be similar to those discovered in holmium laser enucleation of the prostate (HoLEP) group.[55] Some rare complications such as rectal perforation were observed and were thought to be linked to a decrease in the haptic feedback after the transrectal ultrasound scan (TRUS) probe was affixed to the mobile arm.[56]
In 2022 EAU guidelines, aquablation seems to be as effective as TURP, but concerns about the best methods of achieving posttreatment hemostasis still exist (Oxford level of evidence 1b);[57] Aquablation is being investigated and may be administered to patients with moderate-to-severe LUTS and a prostate volume of 30–80 mL as an alternative to TURP (weak recommendation). According to the current AUA guideline on the management of BPH,[58] Aquablation/Robotic waterjet treatment can also serve as a treatment option for patients with LUTS/BPH provided prostate volume 30–80cc, but it has the lowest grade of recommendation (conditional, on a scale from strong to conditional). ATHLETE, a prospective, randomized, open-label, noninferiority trial comparing Aquablation with HoLEP, is being performed at a Swiss center of tertiary care.[59] This trial revealed the efficacy of Aquablation in medium to large prostate, as HoLEP is a well-established approach in the management of prostate glands of 30 mL or larger and is considered the first-line therapy in prostate volume over 80 mL in EAU guidelines.[57]
Water Vapor Thermal Therapy (Rezum)Rezum System (Boston Scientific Company Inc., Marlborough, MA, USA) utilizes convective radiofrequency water vapor to ablate obstructive prostate tissue. The steam was infused into the transition zone of the prostate through a needle inserted into the prostate transurethrally. Once the steam had contact with prostate tissue, the stored thermal energy is released and induces damage to the prostatic cell, and let to tissue necrosis.[60]
The eventual 5-year findings of the multicenter randomized sham-controlled trial assessing 197 patients (mean prostate volume of 45.9 mL in the treatment group) have been accessible lately.[60] McVary et al. revealed that improvement of LUTS was noticed at <3 months after the therapy and the effect remained durable through year 5 of follow-up.[60] IPSS decreased by 48% when compared to baseline, QoL elevated by 45%, and the maximum flow rate was boosted by 44%. In another analysis of 83 patients with large-volume prostates (≥80 mL), IPSS, QoL, and maximum flow rate improvement was shown to be 59%, 70%, and 29% at 12 months following the Rezum procedure, respectively.[61] A retrospective study of 49 patients in urinary retention (with a median PVR of 900 ml) who had Rezum revealed that 6/49 (12.2%) patients stayed in catheter-dependent urinary retention after 6 months of the procedure, even after further surgical intervention for BPH.[62] In a retrospective study of 461 patients undergoing Rezum, the retreatment rate following the procedure was found to be 4.6% and 11/461 (2.4%) cases were within the 1st year.[63] Inadequately treated median lobe, an obstructing bladder neck, and asymmetry of the prostate cavity or recesses were the most prevalent outcomes at reoperation. In the data of 5-year outcomes of Rezum RCT by McVary et al., surgical and medication retreatment rate was found to be 4.4% and 11.1%, respectively.[60] To contrast the efficacy of rezum in medical management for BPH, Gupta et al. employed data from rezum RCT and Medical Therapy of Prostatic Symptoms trial, revealing that LUTS improvement was greater than with either drug alone (doxazosin, finasteride) but comparable to that of combination drugs (P ≤ 0.02 and P = 0.73, respectively).[64]
Concerning the preservation of sexual function, McVary et al. revealed the 5-year outcomes of 197 patients and discovered that rezum induced a modest impact on erectile or ejaculatory function. There were no de novo device or procedure-related erectile dysfunction reported during the study duration.[65] However, the de novo erectile dysfunction rate was discovered to be 3.1% by Mollengarden et al. in a single surgeon retrospective analysis of 129 patients who had the rezum procedure.[66] McVary et al. also discovered that water vapor thermal therapy (WVTT) does not have an overt negative influence on sexual function, unlike conventional medical therapy for BPH.[67] Common adverse events (AEs) linked to the device or procedure after rezum were dysuria, gross hematuria, hematospermia, urinary frequency, AUR, and a decrease in ejaculatory volume in the RCT by McVary et al.[60] Most of these AEs were mild-to-moderate and self-resolved, and no late-onset procedure-related complication was demonstrated in years 1–5.
In 2022 EAU guidelines on the management of male LUTS,[57] no grade of recommendation was known yet. According to the current AUA guideline,[58] rezum/WVTT still has the lowest level of proof and should be deemed a treatment option for patients LUTS/BPH provided prostate volume 30–80 mL (moderate recommendation), and may be recommended to eligible patients who desire the preservation of erectile and ejaculatory function (conditional recommendation). Only one manufacturer-funded double-blind RCT with a follow-up duration of 5 years has been performed currently.[60] More RCTs for rezum against a reference technique (TURP and/or other minimally invasive procedure) are required.
Prostate Artery EmbolizationProstate artery embolization (PAE) employs several embolic agents to blockade prostatic arterial blood flow, facilitating local tissue infarction and necrosis, and further shrinkage of prostate size after necrotic tissue desquamation. Furthermore, the procedure may decrease the level of dihydrotestosterone in the prostate by hindering the entrance of free testosterone from plasma and thus inhibit prostatic tissue growth.[68]
Several prior RCTs have compared the efficacy and safety of PAE to TURP, and one sham-controlled RCT has been published as well.[69],[70] The 2-year follow-up data of RCTs of 103 patients by Abt et al. indicated that the reduction of IPSS after 2 years was 9.21 points following PAE and 12.09 points following TURP. PAE was also shown to be less effective than TURP in the improvement of maximum urinary flow rate (3.9 vs. 10.23 ml/s, in PAE and TURP, respectively), reduction of PVR urine (62.1 vs. 204.0 ml), and reduction of prostate volume (10.66 vs. 30.20 ml).[69] In the first randomized, sham-controlled RCT of 80 men (1:1 in PAE and sham arm) with LUTS/BPH, Pisco et al. indicated that patients in the PAE arm had a higher improvement in IPSS (difference = 13.2 compared to baseline), and a better QoL score at 6 months (difference = 2.13) than patients in the sham arm. Furthermore, the mean difference (MD) in Qmax was 4.2 mL/s.[70] A recent meta-analysis included 6 RCTs and 2 nonrandomized studies contrasting PAE with TURP, and 1 RCT contrasting PAE with sham.[68] The result discovered little to no difference between PAE and TURP in postoperative IPSS (MD 1.72) and QoL (MD 0.28), and that PAE may augment retreatment rates (risk ratio [RR] 3.20) in follow-up duration up to 12 months. In long-term (13–24 months) follow-up, PAE still yielded little to no difference in IPSS (MD 2.58) and IPSS QoL (MD 0.50), with an increased retreatment rate (RR 3.80).
Overall, PAE is linked to fewer complications and a relevant retreatment rate than TURP in RCT by Abt et al.[69] A meta-analysis demonstrated PAE was not greatly correlated with major AEs (Clavien-Dindo Classification III-V), erectile and ejaculatory disorders, AUR, and other minor AEs (Clavien-Dindo Classification I–II).[68] Nonetheless, severe complications had been documented such as penile glans necrosis. This rare condition was believed to be linked to reflux intravascular particles and nontarget embolization and can be managed with hyperbaric oxygen therapy with complete resolution.[71] The retreatment rate of PAE was shown to be 21% after 2 years of procedure in a study by Ray et al., and 19.9% (5.1% in the 1st year and 14.8% thereafter) in an observational UK Register of Prostate Embolization study.[72] The major risks of reoperation included unilateral embolization, median lobe enlargement, small prostate size, and high bladder neck.[72] In a large retrospective study comprising 1072 patients, reintervention rates were 3.4% at 1 year, 21.1% at 5 years, and as high as 58.1% at 10 years.[73]
Current EAU guidelines suggest PAE to men with moderate-to-severe LUTS who wish to consider minimally invasive treatment options and accept less optimal outcomes than TURP (weak recommendation), and only in the department where the workup and follow-up are conducted by urologists working collaboratively with trained interventional radiologists to determine PAE suitable patients (strong recommendation).[57] PAE is not proposed outside the context of clinical trials by the current AUA guidelines on the management of BPH.[58] The data assessing the effectiveness and safety of PAE was restricted, with only 2-year follow-up data available currently. Furthermore, comparative studies are required to determine the benefits and risks of different embolic agents, as innovative embolic agents continue to be employed.[74]
Prostatic Urethral LiftThe prostatic urethral lift (PUL, UroLift System; NeoTract-Teleflex, Pleasanton, CA, USA) employs permanent implants, comprising 2 nitinol anchors linked to nonabsorbable polyethylene terephthalate suture, to displace the prostatic tissue. The procedure is a tissue-sparing method, with one nitinol anchor on the surface of the urethra mucosa and the other found on the outside of the prostate capsule, resulting in retraction of obstructing prostatic lateral or median lobe and further dilatation of prostatic urethra lumen.[75]
Two significant trials assessed the efficacy and safety of PUL when compared to the sham group and TURP.[75] The L.I.F.T analysis was the longest-term multicenter randomized blinded trial of UroLift to date, which included 206 participants with age >50 years, IPPS ≥13, Qmax ≤12 mL/s, and prostate volume of 30–80 mL, and randomized patient to 2:1 (PUL [n = 140], sham treatment [n = 66]).[75] Patients with obstructive median lobe and active UTI were exempted. The AUA-Symptom Score reduction in the PUL arm was 88% higher than that of sham at 3 months (11.1 in PUL and 5.9 in sham), and Qmax increased by 4.3 mL/s (PUL) versus 2.0 mL/s (sham). Advancements in IPSS, QoL, BPH Impact Index (BPH II), and Qmax were sustained through 5 years with improvements of 36%, 50%, 52%, and 44%, respectively. There were no de novo erectile or EjD during the 5-year follow-up. BPH 6 analysis, a prospective RCT involving 80 men, was performed to compare LUTS improvement, recovery, worsening of erectile and ejaculatory functions, continence, and safety in patients that underwent PUL to those of TURP, and 2-year follow-up results have been published.[76] Significant improvements in IPSS, IPSS QoL, BPHII, and Qmax were observed in both treatment groups during the follow-up period. The improvement of IPSS and Qmax were superior in the TURP group, while the PUL group had a superior quality of recovery, ejaculatory function preservation, and performance. The change in IPSS QoL and BPHII was not statistically distinct between the 2 arms. While the obstructive median lobe was deemed exclusion criteria in the L.I.F.T study, the MedLift study, a 2018 nonrandomized prospective study by Rukstalis et al. assessed the utility of PUL in a patient with an obstructive median lobe.[77] The procedure modifies the original method, retracting the intravesically protruding portion of the prostate into the prostatic fossa and fixing prostate tissues laterally to either side of the urethra. Forty-five patients were enrolled and followed for 12 months, and the data was evaluated to previous L.I.F.T lateral lobe enlargement findings. After 12 months of follow-up, mean IPSS enhanced by at least 13.5 from baseline, and QoL and BPHII improved by over 60% and 70%, respectively. The alleviation of symptoms was at least as much comparing the obstructive median lobe group and lateral lobe enlargement group. After combining obstructive median lobe and lateral lobe enlargement data, over 70% of patients indicated ≥8 points improvement in IPSS through 12 months. A meta-analysis of 322 patients with a follow-up period of 24 months was published in 2020,[78] reporting an improvement of IPSS was 9.1 in randomized studies and 10.4 in nonrandomized studies, and that meaningful improvement in Qmax was 3.7 in randomized studies and 3.0 in nonrandomized studies.
AEs following the PUL procedure were mild, including dysuria, gross hematuria, and pelvic pain, which usually resolved in 2–3 weeks. Nonetheless, some pelvic hematoma was self-limiting, and some needed surgical intervention and resulted in renal failure.[79],[80] Another study characterized implant clipping the vesicoureteric junction, leading to groin pain, ureteric obstruction, and hydronephrosis.[81] PUL outperformed TURP in sexual function preservation,[76] and no de novo retrograde ejaculation was discovered. The retreatment rate was relatively high after PUL. The surgical retreatment rate after 2 years in the BPH 6 trial was 5.7% for TURP and 13.6% for PUL[76] and was 13.6% over 5 years in the L.I.F.T trial.[75]
According to the current EAU guidelines, PUL can be given to men interested in preserving ejaculatory function, with prostates <70 mL and no middle lobe (strong recommendation).[57] According to the AUA Guidelines on BPH, PUL should be considered in a patient with LUTS/BPH provided prostate volume 30–80 mL and the confirmed absence of an obstructive middle lobe (moderate recommendation; evidence level: Grade C), and can be given to eligible patients who desire preservation of erectile and ejaculatory function (conditional recommendation; evidence level: Grade C).[58]
The safe and efficacy of PUL in a patient with large prostate or median lobe obstruction had only been assessed in limited studies. Besides, metallic content in implants generates artifacts in magnetic resonance imaging images of the prostate, and the influence of this artifact on prostate cancer imaging evaluation is not extensively studied yet.[82]
Nitinol Butterfly-Like StentThe nitinol butterfly-like stent (i-TIND) (Medi-Tate, Hadera, Israel/Olympus Corporation, Tokyo, Japan) is the second generation of the temporary implantable nitinol device. The device comprises 3 intertwined nitinol struts connected at the distal end and an antimigration anchoring leaflet. After deployment, the struts expand in the urethra, promoting local ischemic necrosis of the prostate at 5, 7, and 12 o'clock positions, influencing the decrease of bladder outlet obstruction.[83],[84]
The MT02 is a prospective, multicenter, single-arm trial, including 81 patients (IPSS ≥10, prostate volume <75 ml, and without obstructing median lobe) at first, with 50 men available for 3 years of follow-up data.[85] Amparore et al. indicated that i-TIND implantation efficacy was durable through 36 months, with averages IPSS, QoL, and Qmax as (20.7–8.55), (3.9–1.76), and (7.71 mL/s to 15.2 mL/s) (baseline to follow-up), improved from baseline by −58.2, −55.6, and + 114.7%.[85] Sexual function was also consistent through 36 months, with no reports of sexual or EjDs. Chughtai et al. reviewed the first comparative data in an RCT (MT03 study), comparing i-TIND to a sham procedure for the treatment of LUTS secondary to BPH.[86] 175 men were included (118 i-TIND and 57 sham). The i-TIND group had a 9.25 decrease in IPSS, a 3.52 ml/s increase in Qmax, and a 1.9 reduction in QoL at 12 months. Most AEs including dysuria and hematuria were mild and only occurred before device removal. In the MT02 study, the surgical retreatment rate was 8.6%, and 6.2% participant-required medication therapy up to 3 years follow-up.[85] In the MT03 study, the surgical reintervention rate and medication usage rate following i-TIND were both 4.7%.[86]
The current EAU guideline considers i-TIND as a technique under investigation and had no recommendation on the usage i-TIND.[57] The AUA guidelines on BPH have not outlined i-TIND yet.[58] Additional studies comparing i-TIND with TURP and other minimally invasive techniques are required. MT-08 trial comparing the effectiveness of i-TIND to UroLift is ongoing and data are presently unavailable.[87]
Future DirectionInitial studies had assessed the effectiveness of several minimally invasive therapies for BPH-related LUTS, while the study design of these trials still had some restrictions, including anatomical consideration (prostate size, obstructive median lobe), reference procedure (TURP or sham), and follow-up duration. Further studies targeting different patient groups (e.g. patients with larger prostate and median lobe, anticoagulant agent usage), with more reference therapies, and an extensive follow-up are required for these minimally invasive therapies. Many minimally invasive therapies are based on the comparable mechanism as i-TIND. The optilume BPH catheter system (Urotronic Inc., Plymouth, Minnesota, USA) is a drug-coated balloon catheter system that delivered an antiproliferative agent to the prostate after dilatation of prostatic urethra with a balloon, and the 1-year outcome had been published.[88] XFLO Expander System (Medeon Biodesign, Inc., Taiwan),[89] Zenflow Spring System (Zenflow, South San Francisco, CA, USA),[90] and Butterfly Prostatic Retraction device (Butterfly, Medical Ltd, Yokneam, Yilit, Israel) adverse are different kinds of nitinol implant for temporary or permanent placement in the urethra and can be deployed with a flexible cystoscope.
ConclusionCombination medical treatments and minimally invasive therapies are prevalently evaluated for treating BPH in recent years. However, minimally invasive therapies have not been developed to totally replace standard BPH surgery but offer an alternative for men unable to undergo standard surgery or those who cannot withstand side-effect of TURP. Many innovative minimally invasive devices for treating BPH are being analyzed.
Data availability statement
All data generated or analyzed during this study are included in this published article.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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