Benign Prostatic Hyperplasia (BPH) Treatment & Management: Approach Considerations, Alpha-Blockers, 5-Alpha-Reductase Inhibitors (2024)

Therapeutic options for benign prostatic hyperplasia (BPH) include the following ^[1] :

• Watchful waiting

• Drug therapy (eg, alpha-blockers,5-alpha-reductase inhibitors)– For patients with bothersome, moderate-to-severe lower urinary tract symptoms (LUTS) from BPH

• Interventional therapy (eg, transurethral resection of the prostate[ TURP]) – For patients with moderate-to-severe LUTS and those who have developed acute urinary retention or other complications of BPH

Watchful waiting is the recommended strategy for patients with BPH who have mild symptoms (International Prostate Symptom Score/American Urological Association Symptom Index [IPSS/AUA-SI] score ≤7) and for those with moderate-to-severe symptoms (IPSS/AUA-SI score ≥8) who are not bothered by their symptoms and are not experiencing complications of BPH. In those patients, medical therapy is not likely to improve their symptoms and/or quality of life (QOL).

In addition, the risks of treatment may outweigh any benefits in such cases. Patients managed expectantly with watchful waiting are usually re-examined annually.

Metabolic syndrome is associated with a higher prevalence and severity of BPH. ^{[11, 12, 13]} Thus, it may be possible to postpone the progression of BPH by lowering blood glucose, improving insulin resistance, and reducing inflammation through a healthy lifestyle and clinical treatment. ^[13]

The era of medical therapy for BPH dawned in the mid 1970s with the use of nonselective alpha-blockers such as phenoxybenzamine. The medical therapeutic options for BPH have evolved significantly since then, with the development of receptor-specific alpha-blockers that comprise current first-line therapy, as well as the approval of 5-alpha-reductase inhibitors.

TURP has long been accepted as the criterion standard for relieving bladder outlet obstruction (BOO) secondary to BPH. In current clinical practice, most patients with BPH do not present with obvious surgical indications; instead, they often have milder lower urinary tract symptoms (LUTS) and, therefore, are initially treated with medical therapy. Several minimally invasive treatments for BOO are also available.

A guideline from the American Urological Association outlines clinical scenarios in which surgery is recommended for LUTS/BPH. The AUA guideline also suggests interventional techniques that can be used as alternatives to TURP (see Guidelines). ^[1]

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Smooth-muscle tension in the prostate stroma, urethra, and bladder neck is thought to be a significant component of LUTS secondary to BPH. The smooth-muscle tension is mediated by alpha-1-adrenergic receptors; therefore, alpha-adrenergic receptor–blocking agents should theoretically decrease resistance along the bladder neck, prostate, and urethra by relaxing the smooth muscle, thus allowing easier passage of urine.

An approximately 4- to 6-point improvement is expected in IPSS/AUA-SI scores when alpha-blockers are used. Interestingly, alpha-blocker therapy has not been shown to reduce the overall long-term risk for acute urinary retention (AUR) or need for BPH-related surgery. ^[14]

The alpha-blocking agents studied in BPH can be subgrouped according to receptor subtype selectivity and the duration of serum elimination half-lives, as follows:

• Nonselective alpha-blockers - Phenoxybenzamine

• Selective short-acting alpha-1 blockers - Prazosin, alfuzosin, indoramin

• Selective long-acting alpha-1 blockers - Terazosin, doxazosin, slow-release (SR) alfuzosin.

• Partially subtype (alpha-1a)–selective agents – Tamsulosin (Flomax), silodosin(Rapaflo)

Nonselective alpha-blockers

Phenoxybenzamine was the first alpha-blocker studied for BPH. It is nonselective, antagonizing both the alpha 1- and alpha 2-adrenergic receptors, which results in a higher incidence of adverse effects. Because of the availability of more alpha-1-receptor–specific agents, phenoxybenzamine is no longer often used for the treatment of BPH. The current American Urological Association (AUA) guideline for BPH retains the statement from the 2003 guideline that insufficient data exist for a recommendation of phenoxybenzamine or of prazosin for treatment of LUTS secondary to BPH. ^[1]

Selective alpha-blockers

The AUA considers alfuzosin, doxazosin, tamsulosin, and terazosin to be appropriate and effective options for treatment of patients with bothersome, moderate-to-severe LUTS secondary to BPH (AUA-SI score ≥8). Although doxazosin and terazosin are older alpha-blockers that require dose titration and blood pressure monitoring, the AUA considers them reasonable choices, as they are inexpensive, are dosed once daily, and appear to be as effective as tamsulosin and alfuzosin. ^[1]

The efficacy of doxazosin and terazosin is dose-dependent. Maximum tolerable doses have not been defined for any alpha-blocker; however, the higher the dose, the more likely the adverse events (orthostatic hypotension, dizziness, fatigue, ejaculatory disorder, nasal congestion).

Three subtypes of the alpha-1 receptor have been identified: 1a, 1b, and 1c. Of these, the alpha-1a receptor is most specifically concentrated in the bladder neck and prostate. Provided that the alpha-1a subtype is predominant in the prostate, bladder neck, and urethra, but not in other tissues, drugs that are selective for this receptor may offer a potential therapeutic advantage.

Two alpha-1a receptor–selective blockers are currently available for symptomatic treatment of BPH: tamsulosin and silodosin. The AUA guidelines do not include recommendations regarding silodosin, asno relevant studies had yet been published in the peer-reviewed literature at the time of its review. ^[1] A more recent Cochrane systematic review, while noting limitations in the available evidence, concluded that the efficacy of silodosin appears similar to that of tamsulosin, naftopidil, and alfuzosin, but the rate of sexual side effects is likely higher. ^[15]

Hellstrom and Sikka reported that the acute administration of tamsulosin affects ejaculatory function and ejaculate volume. Nearly 90% of study subjects experienced decreased ejaculate volume, and approximately 35% experienced anejaculation. In their study, subjects treated with alfuzosin or placebo did not experience anejaculation. ^[16] A randomized controlled trial by Pande et al that compared silodosin with tamsulosin in 53 men with BPH found that the two drugs have comparable efficacy; however, retrograde ejaculation was encountered only with silodosin and postural hypotension only with tamsulosin. ^[17]

Intraoperative floppy iris syndrome

Intraoperative floppy iris syndrome (IFIS) is characterized by miosis, iris billowing, and prolapse in patients undergoing cataract surgery who have taken or currently take alpha-1-blockers. It is particularly prevalent among patients taking tamsulosin. The AUA recommends that clinicians ask patients about planned cataract surgery when offering alpha-blocker therapy for LUTS due to BPH. Alpha-blockers should not be initiated until cataract surgery is completed. ^[1] Patients currently on alpha-blocker therapy must disclose this to their ophthalmologist prior to cataract surgery so that the appropriate preoperative and intraoperative precautions can be taken. Experienced ophthalmologists can thereby reduce the risk of complications from IFIS. ^{[18, 1]}

In a review by Bell et al, exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events, specifically IFIS and its complications (ie, retinal detachment, lost lens or fragments, endophthalmitis). No significant associations were noted with exposure to other alpha-blocker medications or to previous exposure to tamsulosin or other alpha-blockers. ^[19]

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Two5-alpha-reductase inhibitors (5-ARIs) are approved for use in BPH: finasteride (Proscar) and dutasteride(Avodart).American Urological Association (AUA) guidelines advise that in menwith lower urinary tract symptoms (LUTS) and enlarged prostates, 5-ARIsmay help prevent progression of LUTS secondary to BPH and reduce the risk of urinary retention and future prostate-related surgery. The AUA notes that prostatic enlargement can be determined byvolume measurement,prostate-specific antigen (PSA) llevel as a proxy for volume, and/or digital rectal examination. ^[1]

Unlike alpha-blockers, which work by reducing smooth muscle tone,5-ARIs improve LUTS by reducing prostate volume.Thus, patients with larger prostates may achieve a greater benefit. Maximal reduction in prostate volume requires 6 months of therapy.

The role of 5-ARIs inmedical management of BPH emerged from the discovery of a congenital form of pseudohermaphroditism secondary to dihydrotestosterone (DHT) deficiency, which results from a lack of 5-alpha-reductase activity. This deficiency produced a hypoplastic prostate. The two types of 5-alpha-reductase include type 1 (predominantly located in extraprostatic tissues, such as skin and liver) and type 2 (predominantly prostatic reductase).

Inhibition of 5-alpha-reductase type 2 blocks the conversion of testosterone to DHT, resulting in lower intraprostatic levels of DHT. This leads to inhibition of prostatic growth, apoptosis, and involution. The exact role of 5-alpha-reductase type 1 in normal and abnormal prostatic development is undefined.

Finasteride, a 4-aza-steroid, has demonstrated 5-alpha type II–blocking activity, resulting in the inhibition of DHT-receptor complex formation. This effect causes a profound decrease in the concentration of DHT intraprostatically, resulting in a consistent decrease in prostate size. One third of men treated with this agent exhibit improvements in urine flow and symptoms.

In the Proscar Long-Term Efficacy and Safety Study (PLESS), patients treated with finasteride (5 mg/d) were at a significantly lower risk of developing acute urinary retention or needing surgery. ^[20] This was a multicenter, 4-year, double-blind, placebo-controlled study of 3,040 patients. Men with PSA levels of more than 10 ng/mL and those with prostate cancer were excluded.

Dutasteride has an affinity for both type 1 and type 2 5-alpha-reductase receptors. The significance of blockage of type 1 receptors is currently unknown.

Both finasteride and dutasteride actively reduce DHT levels by more than 80%, improve symptoms, reduce the incidence of urinary retention, and decrease the likelihood of surgery for BPH. Adverse effects are primarily sexual in nature (decreased libido, erectile dysfunction, ejaculation disorder).

Both finasteride and dutasteride may reduce serum PSA values by as much as 50%. The decrease in PSA is typically maximally achieved when the maximal decrease in prostatic volume is noted (6 months). This effect must be taken into account when using PSA to screen for prostate cancer.

A prospective, randomized, double-blind study, the Enlarged Prostate International Comparator Study (EPICS), was conducted to compare the efficacy of dutasteride with that of finasteride in men with symptomatic BPH. Although this study was conducted over the course of only 1 year, the data suggest that both drugs were similarly effective in reducing prostate volume and improving maximum urinary flow rate (Qmax) and LUTS for this population. The long-term outcomes are yet to be investigated. ^[21]

Because 5-ARIs interfere with the metabolism of testosterone, pregnant females or those who are considering conception should not handle crushed or broken tablets because of the potential for absorption and subsequent potential risk to a male fetus.

5-alpha reductase inhibitors and prostate cancer

On June 9, 2011, the US Food and Drug Administration (FDA) announced revisions to the prescribing information for 5-ARIs. The FDA advised that prior to initiating therapy with 5-ARIs, clinicians should perform appropriate evaluations to rule out other urological conditions, including prostate cancer, that might mimic BPH.

The FDA's action was based on findings from 2 large, randomized, controlled trials of 5-ARIs for prostate cancer prevention, which reported that trial participants taking 5-ARIs had an increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer). Both trials—the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial—observed a decreased incidence of prostate cancer overall when preventive treatment included 5-ARIs, but an increased incidence of high-grade prostate cancer in men taking dutasteride or finasteride compared with placebo. ^{[22, 23]}

In contrast, a 2015 retrospective cohort study conducted in 13,892 men with a new diagnosis of prostate cancer found that use of 5-ARIs before prostate cancer diagnosis was not associated with an increased risk of prostate cancer-specific mortality (adjusted hazard ratio, [aHR] 0.86) or all-cause mortality (aHR, 0.87). The researchers cite the need for additional studies to replicate these findings. ^[24]

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American Urological Association (AUA) guidelines advise thatcombination therapy with an alpha-blocker and a 5-alpha-reductase inhibitor can be appropriate and effective for patients with lower urinary tract symtpoms (LUTS) who have enlarged prostates. ^[1] The alpha-1-receptor blocker provides rapid relief, while the 5-alpha-reductase inhibitor targets the underlying disease process. ^{[14, 25]} A fixed-dose combination capsule of tamsulosin 0.4 mg and dutasteride 0.5 mg (Jalyn) is approved by the US Food and Drug Administration (FDA) in 2010 for treatment of symptomatic BPH in men with an enlarged prostate.

Landmark clinical trials

The Medical Therapy of Prostatic Symptoms (MTOPS) trial demonstrated that combination therapy reduced the risk of progression and produced a greater improvement in IPSS than therapy with finasteride or doxazosin alone. The risks of acute urinary retention (AUR) and BPH-related surgery were reduced with combination therapy or finasteride in comparison with doxazosin monotherapy. ^[26]

The Symptom Management After Reducing Therapy (SMART-1) trial demonstrated that after 6 months of combination therapy, discontinuation of the alpha-1-blocker is possible in men with moderate LUTS. However, those with severe LUTS may require longer combination therapy. ^[26]

The Medical Therapy of Prostatic Symptoms (MTOPS) trial demonstrated that combination therapy with doxazosin and finasteride was well tolerated, and was superior to placebo and monotherapy with either agent. The primary endpoints of the study were reduction in AUA-SI score, AUR, recurrent infections, kidney insufficiency, incontinence, changes in flow, and PSA level and a lower rate of invasive treatments. MTOPS was a multicenter, 4- to 6-year, double-blind, randomized, placebo-controlled trial of 3,047 men with symptomatic BPH. ^[27]

Four-year results in the Combination of Avodart and Tamsulosin (CombAT) study revealed that for men with prostate volumes of 30-58 mL, combination therapy with dutasteride (dual 5-alpha-reductase inhibitor) and tamsulosin (alpha-1-blocker) improved symptoms, urinary flow, and QOL better than monotherapy with either drug, although not in men who had a prostate volume of 58 mL or more. ^[28] The adverse-effect profile of combination therapy was similar to that of monotherapy, although drug-related adverse events were more common with combination therapy. ^[29]

CombAT was a 4-year, multicenter, randomized, double-blind, parallel group study of 4,844 men aged 50 years or older with moderate-to-severe BPH symptoms (IPSS ≥12), prostate volume of 30 mL or greater, and a PSA level of 1.5-10 ng/mL. This study contributed to the standard of care shifting towards combined drug therapy in appropriately selected patients, while better defining the role of the alpha-blockers. ^[30]

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Phosphodiesterase-5 (PDE5) inhibitors are known to mediate smooth muscle relaxation in the lower urinary tract. The long-acting PDE5 inhibitor tadalafil (Cialis) has been shown to be significantly better than placebo in improving the symptoms of BPH/LUTS. ^{[31, 32]} Tadalafil is approved for treatment of the signs and symptoms of BPH, used alone or withfinasteride (tadalafil 5 mg plus finasteride 5 mg orally, once daily for 26 weeks or less. Tadalifil is also approved for daily use in patients with both BPH and erectile dysfunction(ED).

In patients with BPH who also have ED, the alpha-1 blocker dose should be established first, before treating the ED. The medication used to treat ED should be titrated to the lowest effective dose. If sildenafil is used, doses of greater than 25 mg should not be taken within 4 hours of any alpha-blocker. ^{[33, 34, 35]}

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Historically, anticholinergics were discouraged in men with BPH because of concerns of inducing urinary retention. Trials in patients with BPH have demonstrated a slight increase in post-void residual (PVR) urine volume with the use of anticholinergics; however, acute urinary retention rates were low. Importantly, these trials consisted of patients with low baseline PVR.

The American Urological Association BPH guidelines recommend anticholinergic agents for management of LUTS in patients who do not have an elevated PVR volume and whose LUTS are primarily irritative. Baseline PVR should be measured prior to initiation of anticholinergic therapy, to assess for urinary retention. ^[30] Caution with anticholinergics is recommended with patients whose PVR is greater than 250-300 mL. ^[1]

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A number of herbal formulations and plant-derived compounds have gained popularity worldwide for the management of BPH. ^[36] Phytotherapeutic agents and dietary supplements are considered emerging therapy by the AUA Guidelines panel and are not recommended for the treatment of BPH because of the lack of evidence at this time.

Pharmaceuticals derived from plant extracts are widely used throughout the world for the treatment of various medical ailments. In 1998, Americans spent a total of $3.65 billion on all herbal remedies. In France and Germany, plant extracts have a market share of up to 50% of all drugs prescribed for symptomatic BPH. In the United States, these agents are also popular and readily available.

The attraction to phytotherapeutic agents appears to be related to the perception of therapeutic healing powers of natural herbs, the ready availability, and the lack of adverse effects.

Most of the phytotherapeutic agents used in the treatment of LUTS secondary to BPH are extracted from the roots, seeds, bark, or fruits of plants listed below. Some suggested active components include phytosterols, fatty acids, lectins, flavonoids, plant oils, and polysaccharides. Some preparations derive from a single plant; others contain extracts from 2 or more sources.

Each agent has one or more proposed modes of action. The following modes of action are suggested:

• Antiandrogenic effect

• Antiestrogenic effect

• Inhibition of 5-alpha-reductase

• Blockage of alpha receptors

• Antiedematous effect

• Anti-inflammatory effect

• Inhibition of prostatic cell proliferation

• Interference with prostaglandin metabolism

• Protection and strengthening of detrusor

The origins of phytotherapeutic agents are as follows:

• Saw palmetto, (American dwarf palm; Serenoa repens, Sabal serrulata) fruit

• South African star grass ( Hypoxis rooperi) roots

• African plum tree ( Pygeum africanum) bark

• Stinging nettle ( Urtica dioica) roots

• Rye ( Secale cereale) pollen

• Pumpkin ( Cucurbita pepo) seeds

Saw palmetto (American dwarf palm)

Extracts of saw palmetto berries are the most popular botanical products for BPH. The active components are believed to be a mixture of fatty acids, phytosterols, and alcohols. The proposed mechanisms of action are antiandrogenic effects, 5-alpha-reductase inhibition, and anti-inflammatory effects.

The recommended dosage is 160 mg orally twice daily. Studies show significant subjective improvement in symptoms without objective improvements in urodynamic parameters. Minimal adverse effects include occasional GI discomfort.

The 2010 AUA guidelines, based on more recent studies, do not detect a clinically meaningful effect of saw palmetto on LUTS. Further clinical trials are underway. ^[1] In fact, in a double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites, saw palmetto extract was studied at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. Saw palmetto extract was no more effective than placebo on the American Urological Association Symptom Index. No clearly attributable adverse effects were identified. Similar to the Saw Palmetto Treatment for Enlarged Prostates (STEP) study, saw palmetto was not found to be beneficial for the treatment of LUTS in men. ^[37]

African plum tree (Pygeum africanum)

Suggested mechanisms of action include inhibition of fibroblast proliferation and anti-inflammatory and antiestrogenic effects. This extract is not well studied.

Rye (Secale cereale)

This extract is made from pollen taken from rye plants growing in southern Sweden. Suggested mechanisms of action involve alpha-blockade, prostatic zinc level increase, and 5-alpha-reductase activity inhibition. Significant symptomatic improvement versus placebo has been reported.

Pumpkin seeds(Cucurbita pepo)

Observational studies, retrospective surveys, and randomized controlled trials have provided evidence that pumpkin seeds may reduce urinary urgency and frequency in men with LUTS related to BPH. Adverse effects are mild. Suggested mechanisms of action include increased prostaglandin synthesis, due to their high amounts of linoleic acid, and anti-inflammatory effects from gamma-tocopherol and nitric acid precursors. ^[38]

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TURP is considered the criterion standard for relieving BOO secondary to BPH. The indications to proceed with a surgical intervention include the following:

• Acute urinary retention

• Failed voiding trials

• Recurrent gross hematuria

• Urinary tract infection

• Kidney insufficiency secondary to obstruction

Additional indications for surgical intervention include failure of medical therapy, a desire to terminate medical therapy, and/or financial constraints associated with medical therapy. However, TURP carries a significant risk of morbidity (18%) and a slight mortality risk (0.23%).

TURP is performed with regional or general anesthesia and involves the placement of a working sheath in the urethra through which a hand-held device with an attached wire loop is placed. High-energy electrical cutting current is run through the loop so that the loop can be used to shave away prostatic tissue. The entire device is usually attached to a video camera to provide vision for the surgeon.

Although TURP is often successful, it has some drawbacks. When prostatic tissue is cut away, significant bleeding may occur, possibly resulting in termination of the procedure, blood transfusion, and a prolonged hospital stay. Patients are usually monitored overnight and discharged the following morning, with or without a urinary catheter.

Irrigating fluid may also be absorbed in significant quantities through veins that are cut open, with possible serious sequelae termed transurethral resection (TUR) syndrome. However, this is very rare and does not occur with saline irrigation used in bipolar devices. A urinary catheter must be left in place until the bleeding has mostly cleared.

The large working sheath combined with the use of electrical energy may also result in stricturing of the urethra.

The cutting of the prostate may also result in a partial resection of the urinary sphincteric mechanism, causing the muscle along the bladder outlet to become weak or incompetent. As a result, when the patient ejaculates, this sphincteric mechanism cannot keep the bladder adequately closed. The ejaculate consequently goes backwards into the bladder (ie, retrograde ejaculation), rather than out the penis. Additionally, if the urinary sphincter is damaged, urinary incontinence may result.

The nerves associated with erection run along the outer rim of the prostate, and the high-energy current and/or the heat it generates may damage these nerves, resulting in impotence.

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There is considerable interest in the development of other therapies to decrease the amount of obstructing prostate tissue while avoiding the above-mentioned adverse effects associated with TURP. These therapies are collectively called minimally invasive therapies.

Most minimally invasive therapies rely on heat to destroy prostatic tissue. This heat is delivered in a limited and controlled fashion, in the hope of avoiding the complications associated with TURP. They also allow for the use of milder forms of anesthesia, which translates into less anesthetic risk for the patient.

Heat may be delivered in the form of laser energy, microwaves, radiofrequency energy, high-intensity ultrasound waves, and high-voltage electrical energy. As in TURP, delivery devices are usually passed through a working sheath placed in the urethra, although they are usually of a smaller size than that needed for TURP. Devices may also simply be attached or incorporated into a urinary catheter or passed through the rectum, from which the prostate may also be accessed.

Keep in mind that many of these minimally invasive therapies are undergoing constant improvements and refinements, resulting in increased efficacy and safety. Ask urologists about the specifics of the minimally invasive therapies that they use and what results they have experienced.

Minimally invasive procedures include the following ^[3] :

• Transurethral incision of the prostate (TUIP)

• Laser vaporization or enucleation

• Transurethral microwave therapy (TUMT)

• Transurethral needle ablation of the prostate

• High-intensity ultrasound energy therapy

• Radiofrequency-generated water vapor thermal therapy

• Waterjet ablation therapy

• Mechanical approaches

• Prostatic arterial embolization

Transurethral Incision of the Prostate

TUIP has been in use for many years and, for a long time, was the only alternative to TURP. It may be performed with local anesthesia and sedation. TUIP is suitable for patients with small prostates and for patients unlikely to tolerate TURP well because of other medical conditions. TUIP is associated with less bleeding and fluid absorption than TURP. It is also associated with a lower incidence of retrograde ejaculation and impotence than TURP.

Lasers

Lasers deliver heat to the prostate in various ways. Lasers heat prostate tissue, causing tissue death by coagulative necrosis, with subsequent tissue contraction; however, laser coagulation of the prostate in this specific sense has met with limited results.

Lasers have also been used to directly evaporate, or to melt away, prostate tissue, which is more effective than laser coagulation. Photoselective vaporization of the prostate produces a beam that does not directly come into contact with the prostate; rather, it delivers heat energy into the prostate, resulting in destruction/ablation of the prostate tissue.

GreenLightlasers (American Medical Systems, Minnetonka, USA) and holmium lasers are used to cut and/or enucleate the prostate, similar to the TURP technique. These are widely used laser techniques. Transurethral vaporization/ablation with these lasers can be performed with general or spinal anesthesia and can be performed in an outpatient setting. Catheter time usually lasts less than 24 hours. Photoselective vaporization of the prostate (PVP) with the GreenLight laser has been quite useful in patients who require anticoagulation for various medical conditions, since anticoagulation does not need to be interrupted for this procedure, thus further decreasing patient risk. ^{[39, 40]}

GreenLight lasers are a crystal-enhanced Nd:YAG laser. The first-generation machines used a potassium-titanyl-phosphate (KTP) crystal; the current-generation machines use a lithium-triborate crystal, which allows a higher maximum power output and thus a shorter procedure time. A meta-analysis of 12 studies concluded that GreenLight PVP is safer and more effective than standard TURP in the short and medium-term, but in the long term, patients are more likely to require reoperation due to incomplete vaporization/regrowth of prostatic adenoma. ^[41]

Lasers may be used in a knifelike fashion to directly cut away prostate tissue (ie, holmium laser enucleation of the prostate), similar to a TURP procedure. The holmium laser allows for simultaneous cutting and coagulation, making it quite useful for prostate resection, especially for large prostates. ^[42] Laser enucleation of the prostate has proved to be safe and effective for treatment of symptomatic BPH, regardless of prostate size, with low morbidity and short hospital stay.

TUR syndrome is not seen with this technique, because iso-osmotic saline is used for irrigation. Additionally, removed prostatic tissue is available for histologic evaluation, whereas vaporization/ablation technique does not provide tissue for evaluation. ^{[40, 43]}

Laser treatment usually results in less bleeding and fluid absorption, and shorter hospital stay, as well as decreased incidence of impotence and retrograde ejaculation when compared with standard TURP. However, healing from laser treatment does not occur until after a period when dead cells slough; thus, patients may experience urinary urgency or irritation, resulting in frequent or uncomfortable urination for a few weeks.

The results of laser therapy vary from one another because not all wavelengths yield the same tissue effects. For example, interstitial lasers (eg, indigo lasers) are designed to heat tissue within the confines of the prostate gland and spread radiant energy at relatively low energy levels. They do not directly involve the urethral portion; thus, irritative symptoms following the procedure are potentially reduced.

Contact lasers such as GreenLight or holmium, on the other hand, are designed to cut and vaporize at extremely high temperatures They usually bring about more relief of urinary symptoms than treatment with medicines, but not always as much as is provided with TURP.

Transurethral Microwave Therapy

The use of microwave energy, termed transurethral microwave therapy (TUMT), delivers heat to the prostate via a urethral catheter or a transrectal route. The surface closest to the probe (the rectal or urethral surface) is cooled to prevent injury. The heat causes cell death, with subsequent tissue contraction, thereby decreasing prostatic volume.

TUMT can be performed in the outpatient setting with local anesthesia. Microwave treatment appears to be associated with significant prostatic swelling; a considerable number of patients require a urinary catheter until the swelling subsides. In terms of efficacy, TUMT places between medical therapy and TURP. The 2018 AUA guideline states that TUMT may be offered, but patients should be informed that surgical retreatment rates are higher with TUMT than with TURP. ^[1]

Transurethral Needle Ablation of the Prostate

Transurethral needle ablation of the prostate (TUNA) involves using high-frequency radio waves to produce heat, resulting in a similar process of thermal injury to the prostate as previously described. A specially designed transurethral device with needles is used to deliver the energy.

TUNA can be performed under local anesthesia, allowing the patient to go home the same day. Similar to microwave treatment, radiofrequency treatment is quite popular, and a number of urologists have experience with its use. Radiofrequency treatment appears to reliably result in significant relief of symptoms and better urine flow, although not quite to the extent achieved with TURP. The 2018 AUA guideline does not recommend TUNA for the treatment of BPH. ^[1]

High-Intensity Ultrasound Energy Therapy

High-intensity ultrasound energy therapy delivers heat to prostate tissue, with the subsequent process of thermal injury. High-intensity ultrasound waves may be delivered rectally or extracorporeally and can be used with the patient on intravenous sedation. Urinary retention appears to be common with its use.

High-intensity ultrasound energy also produces moderate results in terms of improvement of the urinary flow rate and urinary symptoms, although its use is now relatively limited compared with the more popular TUNA and TUMT.

High-intensity ultrasound is considered investigational at this time and should not be offered outside of clinical trials.

Radiofrequency-generated Water Thermotherapy

The Rezum system (NxThera, Inc, Maple Grove MN) uses radiofrequency energy to turn sterile water into vapor or steam, which is convectively delivered directly into the obstructive prostate tissue. ^[44] The Rezum procedure has been approved by the FDA for treatment of BPH, and the AUA considers the procedure a viable treatment for BPH (ie, neither investigational nor experimental).

Waterjet Ablation Therapy

Water ablation therapy (Aquablation) uses a high-velocity, non-heated, sterile saline water jet to ablate prostate tissue. The procedure is performed under robotic ultrasound guidance. ^[45] It was approved by the FDA in 2017. ^[3]

American Urological Association guidelines suggest that water ablation therapy may be offered, provided that prostate volume is between 30 and 80 g. ^[1] However, successful use of the procedure in patients with prostate volumes of 80-150 was demonstrated in the Waterjet Ablation Therapy for Endoscopic Resection II study, a prospective, double‐blind, multicenter, international clinical trial. Mean operative time was 37 minutes in these patients, compared with 33 minutes in patients with smaller prostates, and mean change in the International Prostate Symptom Score was comparable; however, the risk of complications was significantly higher. ^[46]

Mechanical Approaches

Mechanical approaches are used less commonly and are usually reserved for patients who cannot have a formal surgical procedure. Mechanical approaches do not involve the use of energy to treat the prostate. They include the prostatic urethral lift (Urolift) and temporary implantable nitinol device (TIND/iTIND). ^[3]

Prostatic stents are flexible devices that can expand when put in place to improve the flow of urine past the prostate. Complications associated with their use include encrustation, pain, incontinence, and overgrowth of tissue through the stent, possibly making their removal quite difficult.

In 2013, the FDA authorized the marketing of the first permanent implant to relieve low or blocked urine flow in men aged 50 years and older with an enlarged prostate. The UroLift system (NeoTract Inc) relieves urine flow by pulling back prostate tissue that is pressing on the urethra. Approval was based on 2 studies of 274 men with BPH implanted with 2 or more UroLift sutures. ^[47] The UroLift was successfully inserted in 98% of participants, and a 30% increase in urine flow and a steady amount of residual urine in the bladder was observed. Patients reported fewer symptoms and improved quality of life in the 2 years following device implantation.

Prostatic Artery Embolization

The incidental discovery that the use of selective prostatic arty embolization (PAE) to control bleeding secondary to BPH resulted in improved LUTS led to investigation of its direct use in the relief of LUTS in patients with BPH. Although a growing body of evidence supports its safety and efficacy, PAE has yet to be established as a standard-of-care treatment option. ^{[48, 49]} A Cochrane review concluded that the impact of PAE on urologic symptoms and improvement in quality of life appears to be similar to that of TURP; however, the review found major uncertainty as to how the major adverse events of the two approaches compare. ^[50]

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Open prostatectomy is now reserved for patients with any of the following:

• A very large prostate (> 75 g)

• Concomitant bladder stones or bladder diverticula

• Inability to be positioned for transurethral surgery.

Open prostatectomy requires hospitalization and involves the use of general/regional anesthesia and a lower abdominal incision. The inner core of the prostate (adenoma), which represents the transition zone, is shelled out, thus leaving the peripheral zone behind. This procedure may involve significant blood loss, necessitating transfusion. Open prostatectomy usually has an excellent outcome in terms of improvement of urinary flow and urinary symptoms.

Laparoscopic simple prostatectomy has been performed at a number of institutions and appears to be feasible. However, prostatectomy performed in this fashion still appears to be associated with risk for significant blood loss. Experience to date with this procedure is limited. ^[51] More recently, robotic-assisted simple prostatectomy has been shown to involve significantly less blood loss and shorter hospital stay but longer operative time compared with open simple prostatectomy. Compared with endoscopic treatments, robotic approaches have a similar perioperative outcome, but cause less urethral trauma or potential bladder neck strictures. ^[52]

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Patients with BPH who have symptoms significant enough to be placed on medication should be evaluated during office visits to discuss the efficacy of the medication and potential dose adjustment. These visits should take place at least biannually. Patients should undergo prostate cancer screening at least annually.

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Data from the Prostate Cancer Prevention Trial revealed that a diet low in fat and red meat and high in protein and vegetables may reduce the risk of symptomatic BPH. Additionally, regular alcohol consumption was associated with a reduced risk of symptomatic BPH, but this is to be interpreted cautiously, given the untoward effects of excessive alcohol consumption. ^[53]

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