Principles of Therapy
The primary treatment goals in benign prostatic hyperplasia are to reduce LUTS, prevent complications, prevent or delay disease progression, and improve prostate-related QoL.
Pharmacological therapy
Benign Prostatic Hyperplasia_Management 1Alpha Blockers
Alpha blockers, also known as alpha-adrenergic antagonists or alpha-adrenergic receptor (alpha-adrenoreceptor) antagonists, act on the smooth muscle tone within the prostate and the bladder neck and produce symptomatic relief within weeks. They bind to and inhibit type 1 alpha-adrenergic receptor and thus inhibit smooth muscle contraction. They may also regulate prostate growth by inducing apoptosis in the epithelial and stromal smooth muscle cells without affecting the rate of cell proliferation. However, they do not alter the natural progression of benign prostatic hyperplasia. They have similar efficacy and the choice is influenced by its ease of use and adverse effects. They are used for patients with symptomatic benign prostatic hyperplasia regardless of prostate size. They may also be given to patients with primary symptoms of bladder outlet obstruction, small prostate and/or PSA ≤1.5 ng/mL.
Selective Long-acting Alpha-1 Adrenergic Antagonists
Selective long-acting alpha-1 adrenergic antagonists include Alfuzosin (slow-release), Doxazosin and Terazosin.
Selective Short-acting Alpha-1 Adrenergic Antagonists
Selective short-acting alpha-1 adrenergic antagonists include Alfuzosin and Prazosin.
Partially Subtype (Alpha-1a)-Selective Adrenergic Antagonists
Partially subtype (alpha-1a)-selective adrenergic antagonists include Silodosin and Tamsulosin.
5-alpha Reductase Inhibitors (5-ARIs)
5-ARIs inhibit 5-alpha reductase, an isoenzyme that metabolizes testosterone to dihydrotestosterone (DHT) in the prostate gland, liver and skin, resulting in the inhibition of the conversion of testosterone to DHT and the reduction of serum and tissue DHT levels. They induce apoptosis of prostate epithelial cells causing reduction in prostate size and decreasing circulating PSA levels after 6-12 months of therapy. They reduce prostate volume, risk of progression to urinary retention and prostatic surgery. They are indicated for patients with significant obstruction and prostate volume >40 mL. ARIS are monotherapy treatment options in patients with prostate volume of >30 mL on imaging, PSA >1.5 ng/dL or palpable prostate enlargement on DRE. They have a slow onset of action (3-6 months) and therefore appropriate only for long-term treatment (years). Monotherapy with 5-ARIs is safe and effective based on systematic reviews.
Dutasteride
Meta-analysis of four randomized controlled trials showed improvement of symptom score and maximum flow rate while decreasing prostate volume, episodes of urinary retention and the need for surgical intervention with Dutasteride.
Finasteride
Finasteride is an azasteroid that inhibits type-2 isoform of 5-alpha reductase which is responsible for the conversion of testosterone to DHT and has anti-androgenic properties. It causes regression of the enlarged prostate to improve symptoms. Data on clinical efficacy persists with long-term treatment (≥6 months). A trial wherein men were treated daily with 5 mg Finasteride showed improvements in symptom scores, maximal urinary flow rates and prostate volume were maintained for >4 years. It may also suppress gross hematuria associated with benign prostatic hyperplasia.
Phosphodiesterase Type 5 (PDE5) Inhibitor
PDE5 inhibitors selectively inhibit PDE5 and increase cyclic guanosine monophosphate (cGMP), which causes smooth muscle relaxation as smooth muscle cells of the prostate and bladder contain PDE5. They are considered in patients with a history of erectile dysfunction (ED) and LUTS secondary to benign prostatic hyperplasia or in patients who failed alpha-adrenergic antagonists or 5-alpha reductase inhibitors. It consistently reduces LUTS associated with benign prostatic hyperplasia. Research has shown that combination therapy with a PDE5 inhibitor and alpha-adrenergic antagonist results in significant improvement in LUTS and ED than alpha-adrenergic antagonist monotherapy. PDE5 inhibitor has rapid onset of action and fewer side effects; it also enhances sexual function and improves QoL.
Tadalafil
A double-blind, placebo-controlled, multicenter study randomized 281 participants who showed significant improvement in the QoL assessment of both irritative and obstructive symptoms and in the IPSS score with Tadalafil.
Benign Prostatic Hyperplasia_Management 2Anticholinergic Agents1
Anticholinergic agents relax bladder smooth muscle by reducing the muscarinic effect of acetylcholine on the smooth muscle. They are used as alternative monotherapy for patients with irritative symptoms (frequency, nocturia and urgency with or without incontinence) related to OAB and without elevated PVR. Placebo-controlled trials showed reduced sensations of urgency, decreased episodes of frequency and urgency incontinence, and increased voided volume.
Darifenacin
Darifenacin is a selective M3 receptor antimuscarinic which has greater selectivity for the muscarinic receptors of the bladder. It is used in the management of urinary frequency, urgency and incontinence in detrusor instability.
Fesoterodine
Fesoterodine is well absorbed, not affected by food, and is metabolized by both the CYP2D6 and CYP3A4 enzyme systems. It is used for the treatment of OAB with urinary urgency, frequency and/or urge incontinence. A pilot study was made for the use of Fesoterodine in the management of OAB and showed a reduction in the IPSS, IPSS irritative sub score, and mean number of nocturia events 7 months after follow up, as well as increase in the QoL.
Oxybutynin
Oxybutynin increases bladder capacity by diminishing bladder muscle contractions. It is used in urinary incontinence, urgency and frequency in the urinary bladder due to neurogenic bladder disorders (eg multiple sclerosis, spina bifida or idiopathic detrusor instability).
Solifenacin
Solifenacin is a selective M3 receptor antagonist and is used for symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency in patients with overactive bladder syndrome (OBS).
Benign Prostatic Hyperplasia_Management 3Tolterodine
Regarding Tolterodine, in one study, the extended-release formulation improved bladder variables among patients who took immediate-release formulation or other anticholinergics.
Trospium
Trospium is a quaternary amine, classified as smooth muscle relaxant. It has limited ability to cross blood-brain barrier and has less impact on cognitive dysfunction. It is used for the treatment of OAB with urinary frequency, urgency and incontinence and nocturia.
Beta-3 Adrenergic Agonist1
Beta-3 adrenergic agonist increases the capacity of the bladder to relax the smooth muscles during the storage phase of urinary bladder filled-void cycle.
Mirabegron
Mirabegron is first in class beta-3 adrenergic agonist for the treatment of OAB. It is used in the management of urinary frequency, urgency, and incontinence in OBS related to benign prostatic hyperplasia. It improves OAB symptoms for which antimuscarinic agents are insufficient. A study revealed that it is safe to utilize because of its low and mild incidences of side effects.
1Please see Overactive Bladder disease management chart for full Dosage Guidelines.
Combined Treatments Containing Alpha-1 Adrenergic Antagonist and 5-Alpha Reductase Inhibitors
Combined treatments containing alpha-1 adrenergic antagonists and 5-alpha reductase inhibitors have the advantage of having rapid onset of symptomatic relief by an alpha-1 adrenergic antagonist and prevention of benign prostatic hyperplasia progression by a 5-ARI. They are used in patients with LUTS associated with demonstrable prostatic enlargement who are at a significant risk of progression, PSA >1.5 ng/dL or on DRE have palpable prostate enlargement. They are used only for long-term treatment (>12 months) and can be an option for patients with prostate volume >30 mL and unresponsive to maximal dose of alpha-1 adrenergic antagonist monotherapy. It must be noted that discontinuation of alpha-1 adrenergic antagonist may be considered after 6-9 months of successful combination therapy.
Dutasteride and Tamsulosin
The 4-year CombAT study provided evidence of the efficacy of Dutasteride and Tamsulosin among patients with larger prostate. It revealed a significant decrease in the IPSS compared with monotherapy.
Finasteride and Doxazosin
Based on the Medical Therapy of Prostatic Symptoms trial (MTOPS) the combination of Finasteride and Doxazosin is more effective than either monotherapy in improving urinary symptoms in men with medium (25 to <40 mL) and large (>40 mL) prostates in long-term treatment.
Combination Treatments Containing Alpha-1 Adrenergic Antagonist and Anticholinergic Agents
Combination treatments containing an alpha-1 adrenergic antagonist and anticholinergic agents can be considered in patients with persistent symptoms of benign prostatic hyperplasia who have irritative symptoms (eg OAB) without an elevated PVR urine volume (≤180 mL). This combination treatment improves QoL and is more effective in reducing urgency urinary incontinence, voiding frequency, nocturia or IPSS compared with alpha-1 adrenergic antagonist alone.
Combination Treatments Containing Alpha-1 Adrenergic Antagonist and Beta-3 Adrenergic Agonist
Combination treatments containing an alpha-1 adrenergic antagonist and beta-3 adrenergic agonist can be considered in patients with moderate to severe predominate storage LUTS.
Alternative Medications
Herbal medications used as a dietary supplement in the treatment of benign prostatic hyperplasia include:
- Saw
palmetto
- The most popular herbal remedy for benign prostatic hyperplasia; extracted from the berry of the plant Serenoa repens
- Extracts from African plum tree (Pygeum africanum), rye grass pollen (Secale cereale), stinging nettle root (Urtica dioica), South African star grass (Hypoxis rooperi) and pumpkin seed oil (Cucurbita peponis)
- Beta-sitosterol, a plant sterol, which is found in some dietary supplements marketed for prostate health
Nonpharmacological
Clinical studies support proper nutrition, avoidance of constipation, weight loss, and regular physical activity as beneficial in improving and preventing urinary symptoms.
Watchful Waiting
Watchful waiting is recommended with yearly follow-up of patients with mild benign prostatic hyperplasia symptoms when other conditions have been excluded.
Lifestyle Changes
Lifestyle changes include:
- Reduce intake of fluids, particularly before going out in public or before periods of sleep (2 hours before bedtime)
- Avoid or reduce intake of caffeinated or alcoholic beverages and spicy foods
- Avoid or monitor use of medications such as decongestants, antihistamines, antidepressants, and diuretics
- Prevent or treat constipation
- Try to achieve and maintain a healthy weight
- Exercise pelvic floor muscles (Kegel exercise)
- Train the bladder to hold more urine for longer periods
- Try to urinate at least once every 3 hours
- “Double voiding” may help (after urinating, wait, and try to urinate again)
- Advise urethral milking to prevent postmicturition dribble
- Perform catheter drainage with urinary retention especially if UTI is present
Surgery
Surgery is recommended when medications are not effective as well as when there are symptoms that are bothersome and severe, when complication arises (eg gross hematuria, renal insufficiency, refractory urinary retention, recurrent UTIs or bladder stones, urinary incontinence, chronic weakening of the bladder) and/or the patient is unwilling to undergo or develops adverse effects from medical therapy. The choice of surgical technique is dependent on prostate size, presence of comorbidities, ability of the patient to have anesthesia, patient’s preference and willingness to accept surgery-associated side effects, availability of surgical equipment, and the surgeon’s experience and preference. Patients are counseled regarding the potential risks of treatment failure and the need for additional therapies when surgical and minimally-invasive treatments are considered for LUTS secondary to benign prostatic hyperplasia. Retreatment may be a medical therapy, a minimally-invasive intervention or a surgical procedure with the types of and thresholds for retreatment varying by patient, provider, initial treatment modality and type of treatment failure (ie objective, subjective or both).
Transurethral Resection of the Prostate (TURP)
Benign Prostatic Hyperplasia_Management 4
TURP is the most common surgical treatment for benign prostatic hyperplasia. It is the standard procedure for patients with prostate volume >30 mL but <80 mL and bothersome symptoms secondary to benign prostatic obstruction (BPO). It is the gold standard in treating the blockage of the urethra due to benign prostatic hyperplasia. Resectoscope is inserted into the urethra to reach the prostate gland then pieces of tissue are scraped and removed using a heated wire loop.
Ejaculatory-Preserving TURP
Ejaculatory-preserving TURP utilizes surgical techniques which preserves tissues essential for ejaculation. It has significant preservation rates of ejaculation compared to classic TURP.
Open Prostatectomy
Open prostatectomy is done when the prostate is greatly enlarged, complication arises, bladder is damaged or repair is needed. It is the most invasive surgical procedure for the treatment of BPO. In open prostatectomy, an incision is made and part or all of the prostate gland is removed. The procedure requires general anesthesia, longer hospital stay and rehabilitation period. The recovery period varies from 3-6 weeks.
Laser Treatments
In laser treatments, a cystoscope is used to pass a laser fiber into the urethra to the prostate and a high-energy laser is used to destroy prostate tissue.
Diode Laser Vaporization of the Prostate
Diode laser vaporization of the prostate is an option for patients on anticoagulants. It has been shown to have high intra-operative safety and with shorter catheterization and hospital times compared to TURP.
Holmium Laser Enucleation of the Prostate (HoLEP)
HoLEP is used to enucleate the prostate adenoma by using end firing pulsed solid state laser. It is an option for patients with varying prostate sizes and patients at higher risk of bleeding such as those on anticoagulants. It has the same result as TURP with fewer complications. Furthermore, it has shorter catheterization and hospital times, reduced blood loss but with longer operation time compared to TURP.
Holmium Laser Resection of the Prostate (HoLRP)
HoLRP uses laser-generated heat to remove prostate tissue obstructing the urethra. It has shorter catheterization and hospitalization times compared to TURP.
Photoselective Vaporization of the Prostate (PVP)
Using 120W or 180W platforms, PVP is an option for patients with small- and average-sized prostates. It is an option for patients at higher risk of bleeding such as those on anticoagulants or patients with a high cardiovascular (CV) risk. It utilizes 600-micron side firing laser with a wavelength of 532 nm in a non-contact mode. The prostate adenoma is vaporized sequentially outwards until the surgical capsule is exposed and a defect is created within the prostate parenchyma through which the patient will void. It has shorter catheterization and hospital times and with reduced clot retention but longer operating time compared to TURP.
Thulium Laser Enucleation of the Prostate (ThuLEP)
ThuLEP is an alternative to open prostatectomy or HoLEP in patients with moderate-severe LUTS and prostate volumes >80 mL. It is an option for patients with varying prostate sizes and patients at higher risk of bleeding such as those on anticoagulants. It is associated with lower rates of bleeding and complications compared to TURP and open simple prostatectomy.
Transurethral Incision of the Prostate (TUIP)
TUIP is a treatment option for patients with prostate volume ≤30 mL without a middle lobe. It is a procedure that widens the urethra of patients with mildly enlarged prostate glands. A cystoscope is inserted and electric current or laser beam is used to reach the urethra going to the prostate. A Foley catheter is inserted after the procedure to freely drain the urine out of the bladder. It demonstrates lower rates of ejaculatory dysfunction compared to traditional TURP.
Complications of Invasive Procedures
Complications of invasive procedures include:
- Problems urinating
- Urinary incontinence
- Bleeding and blood clots
- Urethral strictures
- Bladder neck contracture
- Infection
- Scar tissue
- Sexual/erectile dysfunction
- Recurring problems such as urinary retention and UTIs
- Retrograde ejaculation
Minimally Invasive Surgical Therapies (MISTs)
MISTs are transurethral methods that use catheter or cystoscope to reach the prostate and may require local, regional or general anesthesia. The procedures are decided based on the patient’s symptoms and overall health.
Aquablation
Aquablation is an option for patients with prostate volume >30 mL but <80 mL with or without middle lobe and desiring ejaculatory function preservation. It utilizes a transurethrally placed robotic handpiece, console and conformal planning unit (CPU) to resect the prostate using a water jet followed by hemostasis through electrocautery with cystoscope or resectoscope or traction from a 3-way catheter balloon. This procedure requires general anesthesia.
High-Intensity Focused Ultrasound
High-intensity focused ultrasound, also known as histotripsy, uses an ultrasound probe inserted onto the rectum near the prostate. In this procedure, waves are used to heat and destroy the enlarged prostate tissue.
Minimal Invasive Simple Prostatectomy
Minimally invasive simple prostatectomy includes laparoscopic simple prostatectomy (LSP) and robot-assisted simple prostatectomy (RASP). This may be an option for patients with prostate volume >80 mL but more randomized controlled trials are needed to evaluate long-term efficacy and safety.
Prostate Artery Embolization (PAE)
PAE is a newer MIST endorsed by the Society of Interventional Radiology and National Institute for Health and Care Excellence (NICE) for the treatment of benign prostatic hyperplasia in the UK but not recommended for treatment by the American Urological Association (AUA) and used only in clinical trials in the USA. It may be an alternative for patients who are not good candidates for surgery due to comorbidities and those with prostate volume >80-100 mL.
Prostatic Stent Insertion
Prostatic stent insertion is an option for patients not suitable for surgery but with a functional detrusor muscle. The prostatic stent is inserted to the narrowed area caused by the enlarged prostate; the stent expands like a spring in place and pushes back the prostate tissue to widen the urethra. It may be used in men who are unable to tolerate other procedures.
Prostatic Urethral Lift (PUL)
PUL is an option for patients with prostate volume <80 mL and without obstructive middle lobe and for eligible patients wanting to preserve erectile and ejaculatory function. This procedure compresses encroaching lateral lobes by placing small, permanent, suture-based nitinol tabbed implants delivered through a cystoscope.
Transurethral Microwave Therapy (TUMT)
In TUMT, a catheter with antenna is inserted into the urethra to reach the prostate and microwaves are sent to heat and destroy the selected portions of the gland. Cystoscopy is necessary prior to the procedure to determine the presence of a middle lobe or an insufficient length of prostatic urethra. It is an alternative for elderly patients with comorbidities or greater anesthesia risk.
Transurethral Needle Ablation (TUNA)
In TUNA, a cystoscope with a needle at the end is inserted to send the radiofrequency to heat and destroy the selected prostate tissue. It is a treatment option in Europe but is not recommended in the USA and Canada. It is not recommended for prostate size >75 mL or isolated bladder neck obstruction and in the presence of a middle lobe.
Transurethral Vaporization of the Prostate (TUVP)
TUVP may be an alternative for patients with prostate volume of 30-80 mL and moderate-severe LUTS. In TUVP, a resectoscope with electrode is inserted to the urethra and moved across the prostate to transmit electric current to vaporize prostate tissue.
Water Vapor Thermal Therapy
Water vapor thermal therapy is also known as transurethral destruction of prostate tissue by radiofrequency-generated water thermotherapy. It is an option for patients with prostate volume <80 mL or with median lobe and for eligible patients wanting to preserve erectile and ejaculatory function. In this procedure, a catheter with a treatment balloon is used to heat and destroy the tissue. It can target specific region of the prostate while the tissues surrounding the urethra and bladder remain protected.
Complications of MISTs
Complications of MISTs include:
- UTIs
- Painful urination
- Difficulty urinating
- An urgent or a frequent need to urinate
- Urinary incontinence
- Blood in the urine for several days after the procedure
- Sexual dysfunction
- Chronic prostatitis
- Recurring problems such as urinary retention and UTIs