madman
Super Moderator
Update on the management of benign prostatic hyperplasia and the role of minimally invasive procedures (2023)
Juan V.A. Franco,Pablo Tesolin, Jae Hung Jung
Abstract
Lower urinary tract symptoms due to benign prostatic hyperplasia constitute a substantial burden, affecting the quality of life of those affected by this condition. While watchful waiting and medical management using a wide array of pharmaceuticals can be effective, surgery has been one of the most definite solutions for those highly affected by this condition. Transurethral resection of the prostate (TURP) is the gold standard surgical procedure, but other alternatives using laser (HoLEP and ThuLEP) and robotic water jets (Aquablation) are emerging treatments aimed at reducing postoperative morbidity. Minimally invasive procedures conducted in outpatient settings and under local anesthesia or sedation are increasingly being used, especially in those patients with high surgical risk due to comorbidities. These procedures include prostatic arterial embolization, water vapor thermal therapy (Rezum), prostatic urethral lift (Urolift), temporary implantable nitinol device (TIND/iTIND), and transurethral microwave thermotherapy (TUMT). The evidence supporting these treatments is growing, but some uncertainties remain as to what is the magnitude of their advantages and disadvantages compared to TURP. Innovations in the technologies involved in these new procedures may improve their profile for effectiveness and safety. Moreover, new devices are being investigated for marketing approval. Issues around costs and patients’ preferences are also yet to be elucidated, thus their evolving role needs to be weighed against the aforementioned considerations.
1. Introduction
Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland due to androgenic stimulus exerted by dihydrotestosterone, a metabolite derived from testosterone by the action of the enzyme 5-alpha reductase.1 The most important risk factors for developing BPH include age and the presence of functioning testicles (due to their hormonal influence); a family history of this condition and obesity.2 A total of 50% of 60-year-old men and 90% of 85-year-olds have microscopic BPH; however, only 50% of patients with this histological finding will have a macroscopic enlargement of the gland, and about 50% of these will develop symptoms.3 Therefore, the most appropriate name for this entity is “lower urinary tract symptoms” (LUTS), considering that prostate enlargement is only one of the factors related to the presence of symptoms. The prevalence of LUTS is between 10% and 30% for men in their 60-70s and 30% in their 80s.4
Patients may present with obstructive or irritative symptoms.1 Diagnosis is based on clinical history, and complementary studies are very useful to evaluate the degree of obstruction, rule out complications, and exclude other differential diagnoses.1 Disease severity can be assessed using valid questionnaires, including the International Prostate Symptom Score (IPSS), which consist of seven questions rated on a 0-5 Likert scale, and the total score ranges from 0 to 35.5 Based on the sum score, symptoms can be classified as mild (0-7), moderate,8-19 or severe.20-35 An additional question rates from 0 to 6 the overall impact on the quality of life (IPSS-QoL).5 Long-term complications of BPH include acute urinary retention (AUR), recurrent urinary tract infections, bladder stones, and post-obstructive kidney failure. AUR is one of the most frequent complications, and the risk is up to 14% in 10 years in patients with large prostates and moderate to severe symptoms.6
2. Medical management
The natural history of BPH shows that the progression of symptoms is very slow, and serious complications are infrequent. Watchful waiting and lifestyle modifications may be warranted in those with mild symptoms. Physical activity could reduce the symptoms of prostatism, so the recommendation to exercise regularly could be part of this management strategy.7 Clinicians frequently advise avoiding irritants, such as coffee, spicy foods, and alcohol, although there is little to no evidence to support these recommendations.8
For those with moderate symptoms, alpha-blockers are the first treatment option, reducing symptoms by 30-40% and improving urinary flow by 20-25%.9 Common side effects include hypotension and ejaculatory dysfunction. However, 5-alpha reductase inhibitors (5-ARI) can cause a moderate reduction in symptoms (15-30%) and prostate size, reducing the risk of AUR and the need for surgery, but there is a latency for this improvement (3-6 months), and they are most effective in patients with larger prostates (>30 ccs) that will be treated on a long-term basis.9,10 Patients should be warned that side effects include sexual dysfunction (e.g. erectile and ejaculatory disorder). In highly symptomatic patients with large prostates, the combined use of alpha-blockers and 5-ARI can result in faster symptomatic improvement and a reduction in the incidence of long-term complications.
Other drugs can be considered in the presence of specific symptoms. The result of clinical trials of phosphodiesterase inhibitors (PDE-Is) such as tadalafil indicates that they may be marginally beneficial over a placebo in reducing LUTS.11 While there is a potential risk of hypotension in combination with alpha-adrenergic blockers, a recent meta-analysis reported that concomitant treatment with a-blockers and PDE-Is does not increase the rate of adverse events due to hypotension.12 Tadalafil may be considered in patients with persistent symptoms in the context of concomitant erectile sexual dysfunction, although it requires close monitoring of adverse events. Moreover, LUTS due to BPH may coexist with symptoms of urgency, frequency, and incontinence due to detrusor overactivity (i.e. overactive bladder). In these cases, beta-3 adrenergic agonists, such as mirabegron and vibegron, stimulate detrusor relaxation without compromising bladder contractility. According to the available clinical trials, they would be effective in reducing irritative symptoms.13 They can be used alone or in combination with anticholinergics. Common side effects include an increase in blood pressure.
Phytotherapeutic agents, such as Serenoa repens, also called Sabal serrulatum or Saw palmetto, have failed to demonstrate symptomatic relief in multiple clinical trials against a placebo.14 Pumpkin seeds (Cucurbita pepo) and African plum (Pygeum africanum) in some small clinical trials have moderate efficacy in reducing symptoms.15 These drugs have fewer adverse events, but considering their limited effectiveness, their role in treating LUTS is limited.
3. Surgery and minimally invasive procedures
Transurethral resection of the prostate (TURP) is one of the most widely used techniques, and the probability of symptomatic improvement with this treatment is between 75% and 96%, and it is considered the “gold standard” treatment. The intervention is brief (usually within 60 minutes) and requires general or spinal anesthesia. The tissue is removed through the urethra using a resectoscope, and the patient remains with a bladder catheter for approximately a couple of days, and after this period, he is discharged from the hospital.16 The morbidity associated with TURP varies between 5% and 30%. Intraoperative complications include uncontrollable bleeding and capsular perforation with the consequent massive absorption of irrigation fluid (“post-TURP syndrome”) and its consequences of dilutional hyponatremia, acute renal failure due to hemolysis, cerebral edema, and even death.17 Early postoperative complications include hematuria, which may persist for up to six weeks, and infection; whereas, late complications include urethral stricture (<10%), bladder neck fibrosis, and urinary incontinence (~1%).18,19 The most frequent late adverse effect of TURP is retrograde ejaculation (66% to 86% of operated patients); it can produce sterility but is not accompanied by alterations when achieving orgasm. Between 10% and 15% of patients present with psychogenic erectile dysfunction after TURP, and up to 2% to 5% with surgery-derived erectile dysfunction.20,21 The reoperation rate is close to 3.3%, mostly related to the aforementioned late complications.22,23 Improvements in the TURP technique, including the use of bipolar energy, have reduced the risk of post-TUR syndrome and bleeding.23
4. Alternatives to TURP with spinal anesthesia
There are currently several surgical procedures with laser devices for the treatment of BPH, which allow the use of saline solution as an irrigation medium (with the same advantages as bipolar TURP) and are performed on an outpatient basis under spinal anesthesia with a requirement bladder catheter that averages 24 to 48 hours.24 Laser enucleation uses a technique that, similar to open surgery, consists of resecting the middle and lateral lobes from the verumontanum to the bladder neck and then grinding the surgical material in the bladder for pathological study using Holmium (HoLEP) or Thulium (ThuLEP) lasers. This procedure offers results comparable to TURP with less morbidity and hospital stay.24,25
Laser ablation, on the other hand, is a technique that uses lasers to cauterize glandular tissue until an adequately patent prostatic canal is achieved. Similarly, photo-selective vaporization of the prostate (PVP) uses green light for this purpose.26 The disadvantages of ablation and vaporization procedures include the impossibility of obtaining material for biopsy and a time of dysuria that is usually longer than with TURP; whereas, the advantages over the latter are a shorter hospital stay, subsequent bleeding, and the need for a bladder catheter, with similar results in terms of symptom improvement.25,26
Finally, water ablation therapy (also known as Aquablation®) is a recently developed surgical procedure that, using real-time visualization and ultrasound, uses a high-velocity, non-heated, sterile saline water jet to ablate prostate tissue. This procedure is probably as effective as TURP with a lower incidence of ejaculation problems, but no little difference in erectile function.27
5. Alternatives to TURP using local anesthesia or sedation:
Many patients with moderate or severe symptoms are older adults with a high surgical risk, which led to the emergence of minimally invasive alternatives that, unlike the aforementioned procedures, can be performed with local anesthesia, on an outpatient basis, and selective post-procedure catheterization. These procedures, with the exception of arterial embolization, in principle, are not designed for large prostates. These procedures include as follows:
*Prostatic arterial embolization (PAE)
*Prostatic urethral lift (PUL, Urolift®, Teleflex Inc., Pleasanton, CA, USA)
*Temporary implantable nitinol device (TIND®, Medi-Tate Ltd., Hadera, Israel)
*Water vapor thermal therapy (WVTT, Rezum®, NxThera Inc., Maple Grove, MN, USA)
*Transurethral microwave thermotherapy (TUMT)
5.1. Benefits and harms of minimally invasive procedures
5.2. Finding the right spot for new treatments e what comes next?
Juan V.A. Franco,Pablo Tesolin, Jae Hung Jung
Abstract
Lower urinary tract symptoms due to benign prostatic hyperplasia constitute a substantial burden, affecting the quality of life of those affected by this condition. While watchful waiting and medical management using a wide array of pharmaceuticals can be effective, surgery has been one of the most definite solutions for those highly affected by this condition. Transurethral resection of the prostate (TURP) is the gold standard surgical procedure, but other alternatives using laser (HoLEP and ThuLEP) and robotic water jets (Aquablation) are emerging treatments aimed at reducing postoperative morbidity. Minimally invasive procedures conducted in outpatient settings and under local anesthesia or sedation are increasingly being used, especially in those patients with high surgical risk due to comorbidities. These procedures include prostatic arterial embolization, water vapor thermal therapy (Rezum), prostatic urethral lift (Urolift), temporary implantable nitinol device (TIND/iTIND), and transurethral microwave thermotherapy (TUMT). The evidence supporting these treatments is growing, but some uncertainties remain as to what is the magnitude of their advantages and disadvantages compared to TURP. Innovations in the technologies involved in these new procedures may improve their profile for effectiveness and safety. Moreover, new devices are being investigated for marketing approval. Issues around costs and patients’ preferences are also yet to be elucidated, thus their evolving role needs to be weighed against the aforementioned considerations.
1. Introduction
Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland due to androgenic stimulus exerted by dihydrotestosterone, a metabolite derived from testosterone by the action of the enzyme 5-alpha reductase.1 The most important risk factors for developing BPH include age and the presence of functioning testicles (due to their hormonal influence); a family history of this condition and obesity.2 A total of 50% of 60-year-old men and 90% of 85-year-olds have microscopic BPH; however, only 50% of patients with this histological finding will have a macroscopic enlargement of the gland, and about 50% of these will develop symptoms.3 Therefore, the most appropriate name for this entity is “lower urinary tract symptoms” (LUTS), considering that prostate enlargement is only one of the factors related to the presence of symptoms. The prevalence of LUTS is between 10% and 30% for men in their 60-70s and 30% in their 80s.4
Patients may present with obstructive or irritative symptoms.1 Diagnosis is based on clinical history, and complementary studies are very useful to evaluate the degree of obstruction, rule out complications, and exclude other differential diagnoses.1 Disease severity can be assessed using valid questionnaires, including the International Prostate Symptom Score (IPSS), which consist of seven questions rated on a 0-5 Likert scale, and the total score ranges from 0 to 35.5 Based on the sum score, symptoms can be classified as mild (0-7), moderate,8-19 or severe.20-35 An additional question rates from 0 to 6 the overall impact on the quality of life (IPSS-QoL).5 Long-term complications of BPH include acute urinary retention (AUR), recurrent urinary tract infections, bladder stones, and post-obstructive kidney failure. AUR is one of the most frequent complications, and the risk is up to 14% in 10 years in patients with large prostates and moderate to severe symptoms.6
2. Medical management
The natural history of BPH shows that the progression of symptoms is very slow, and serious complications are infrequent. Watchful waiting and lifestyle modifications may be warranted in those with mild symptoms. Physical activity could reduce the symptoms of prostatism, so the recommendation to exercise regularly could be part of this management strategy.7 Clinicians frequently advise avoiding irritants, such as coffee, spicy foods, and alcohol, although there is little to no evidence to support these recommendations.8
For those with moderate symptoms, alpha-blockers are the first treatment option, reducing symptoms by 30-40% and improving urinary flow by 20-25%.9 Common side effects include hypotension and ejaculatory dysfunction. However, 5-alpha reductase inhibitors (5-ARI) can cause a moderate reduction in symptoms (15-30%) and prostate size, reducing the risk of AUR and the need for surgery, but there is a latency for this improvement (3-6 months), and they are most effective in patients with larger prostates (>30 ccs) that will be treated on a long-term basis.9,10 Patients should be warned that side effects include sexual dysfunction (e.g. erectile and ejaculatory disorder). In highly symptomatic patients with large prostates, the combined use of alpha-blockers and 5-ARI can result in faster symptomatic improvement and a reduction in the incidence of long-term complications.
Other drugs can be considered in the presence of specific symptoms. The result of clinical trials of phosphodiesterase inhibitors (PDE-Is) such as tadalafil indicates that they may be marginally beneficial over a placebo in reducing LUTS.11 While there is a potential risk of hypotension in combination with alpha-adrenergic blockers, a recent meta-analysis reported that concomitant treatment with a-blockers and PDE-Is does not increase the rate of adverse events due to hypotension.12 Tadalafil may be considered in patients with persistent symptoms in the context of concomitant erectile sexual dysfunction, although it requires close monitoring of adverse events. Moreover, LUTS due to BPH may coexist with symptoms of urgency, frequency, and incontinence due to detrusor overactivity (i.e. overactive bladder). In these cases, beta-3 adrenergic agonists, such as mirabegron and vibegron, stimulate detrusor relaxation without compromising bladder contractility. According to the available clinical trials, they would be effective in reducing irritative symptoms.13 They can be used alone or in combination with anticholinergics. Common side effects include an increase in blood pressure.
Phytotherapeutic agents, such as Serenoa repens, also called Sabal serrulatum or Saw palmetto, have failed to demonstrate symptomatic relief in multiple clinical trials against a placebo.14 Pumpkin seeds (Cucurbita pepo) and African plum (Pygeum africanum) in some small clinical trials have moderate efficacy in reducing symptoms.15 These drugs have fewer adverse events, but considering their limited effectiveness, their role in treating LUTS is limited.
3. Surgery and minimally invasive procedures
Transurethral resection of the prostate (TURP) is one of the most widely used techniques, and the probability of symptomatic improvement with this treatment is between 75% and 96%, and it is considered the “gold standard” treatment. The intervention is brief (usually within 60 minutes) and requires general or spinal anesthesia. The tissue is removed through the urethra using a resectoscope, and the patient remains with a bladder catheter for approximately a couple of days, and after this period, he is discharged from the hospital.16 The morbidity associated with TURP varies between 5% and 30%. Intraoperative complications include uncontrollable bleeding and capsular perforation with the consequent massive absorption of irrigation fluid (“post-TURP syndrome”) and its consequences of dilutional hyponatremia, acute renal failure due to hemolysis, cerebral edema, and even death.17 Early postoperative complications include hematuria, which may persist for up to six weeks, and infection; whereas, late complications include urethral stricture (<10%), bladder neck fibrosis, and urinary incontinence (~1%).18,19 The most frequent late adverse effect of TURP is retrograde ejaculation (66% to 86% of operated patients); it can produce sterility but is not accompanied by alterations when achieving orgasm. Between 10% and 15% of patients present with psychogenic erectile dysfunction after TURP, and up to 2% to 5% with surgery-derived erectile dysfunction.20,21 The reoperation rate is close to 3.3%, mostly related to the aforementioned late complications.22,23 Improvements in the TURP technique, including the use of bipolar energy, have reduced the risk of post-TUR syndrome and bleeding.23
4. Alternatives to TURP with spinal anesthesia
There are currently several surgical procedures with laser devices for the treatment of BPH, which allow the use of saline solution as an irrigation medium (with the same advantages as bipolar TURP) and are performed on an outpatient basis under spinal anesthesia with a requirement bladder catheter that averages 24 to 48 hours.24 Laser enucleation uses a technique that, similar to open surgery, consists of resecting the middle and lateral lobes from the verumontanum to the bladder neck and then grinding the surgical material in the bladder for pathological study using Holmium (HoLEP) or Thulium (ThuLEP) lasers. This procedure offers results comparable to TURP with less morbidity and hospital stay.24,25
Laser ablation, on the other hand, is a technique that uses lasers to cauterize glandular tissue until an adequately patent prostatic canal is achieved. Similarly, photo-selective vaporization of the prostate (PVP) uses green light for this purpose.26 The disadvantages of ablation and vaporization procedures include the impossibility of obtaining material for biopsy and a time of dysuria that is usually longer than with TURP; whereas, the advantages over the latter are a shorter hospital stay, subsequent bleeding, and the need for a bladder catheter, with similar results in terms of symptom improvement.25,26
Finally, water ablation therapy (also known as Aquablation®) is a recently developed surgical procedure that, using real-time visualization and ultrasound, uses a high-velocity, non-heated, sterile saline water jet to ablate prostate tissue. This procedure is probably as effective as TURP with a lower incidence of ejaculation problems, but no little difference in erectile function.27
5. Alternatives to TURP using local anesthesia or sedation:
Many patients with moderate or severe symptoms are older adults with a high surgical risk, which led to the emergence of minimally invasive alternatives that, unlike the aforementioned procedures, can be performed with local anesthesia, on an outpatient basis, and selective post-procedure catheterization. These procedures, with the exception of arterial embolization, in principle, are not designed for large prostates. These procedures include as follows:
*Prostatic arterial embolization (PAE)
*Prostatic urethral lift (PUL, Urolift®, Teleflex Inc., Pleasanton, CA, USA)
*Temporary implantable nitinol device (TIND®, Medi-Tate Ltd., Hadera, Israel)
*Water vapor thermal therapy (WVTT, Rezum®, NxThera Inc., Maple Grove, MN, USA)
*Transurethral microwave thermotherapy (TUMT)
5.1. Benefits and harms of minimally invasive procedures
5.2. Finding the right spot for new treatments e what comes next?
