Benign Prostatic Hyperplasia

Background

Benign prostatic hyperplasia (BPH) is one of the most common conditions affecting the prostate. It is also called benign prostatic enlargement (BPE) and prostatism. It falls under the category of ‘lower urinary tract symptoms’ (LUTS). Technically speaking, BPH is a histologic diagnosis which means that a sample of tissue is required to make a diagnosis. Practically, however, BPH is diagnosed when a man presents with a constellation of symptoms suggestive of the condition and may even occur in the absence of an enlarged prostate. Having said that, many urinary symptoms in males are unrelated to BPH or only partly explained by BPH. The story is often a bit more complicated than this but most people find it easiest to think of BPH as ‘choking off’ the pipe (the urethra) that drains the bladder.

The incidence of BPH increases with age and is found in approximately a 50% of men at age 60 and 90% at age 85. Some of these men will have severe symptoms.

 

Causes

There are multiple reasons for age related changes within the prostate resulting in enlargement and outlet obstruction. These include:

  1. Genetic predisposition. BPH tends to run in family's.

  2. Environmental factors and lifestyle choices. More on this below.

  3. hormonal changes which occur with aging

The symptoms from BPH have classically been described as a result from obstruction of the bladder outlet but in reality the picture is more complicated. There may be other co-existing conditions and the response of the bladder to the obstruction introduces additional symptoms.

Your physician will seek other explanations or contributing causes for a patient’s urinary symptoms. These include medications, infections, neurological diseases, urethral strictures, overactive bladder, and cancer.

Symptoms and Risks of BPH

At the risk of oversimplifying, the mechanism by which BPH causes problems the following explanation is provided: the prostate grows with age, chokes off the urethra and causes a spectrum of urinary symptoms and serious complications.

  • Some of the consequences of bladder outlet obstruction are obvious but some are not. The following symptoms may indicate a problem with the prostate but sometimes there are other causes (e.g. urethral strictures, medications, neurological conditions).

    When the prostate chokes of the pipe problems arise. The most common problems caused by BPH are urinary symptoms:

    • Difficulty initiating the stream (hesitancy).

    • Slow stream.

    • Needing to push or strain to urinate.

    • Stream stops and starts (intermittency).

    • Difficulty emptying the bladder or incomplete emptying.

    • Urine keeps coming after you want to stop (post-void dribble).

    • Needing to return to the washroom soon after you have urinated (double or triple voiding).

    • Frequent urination, day and/or night.

    • Leakage of urine (urinary incontinence).

    • Inability to postpone urination (urinary urgency).

    Urinary retention: This is an inability to empty the bladder. It may be partial or complete. When the urine cannot be emptied it may back up to the kidneys and causes life-threatening complications such as kidney failure. In some cases, ‘overflow’ urinary incontinence will occur where men have to constantly urinate and drip urine almost all the time, especially at night. It is called ‘overflow’ since it is analogous to an overflowing sink because of a blocked drain - with the difference that the fluid comes from the kidney rather than a tap.

    Urinary frequency: If the bladder incompletely empties, frequent urination or waking at night may result as a consequence of a reduction in the functional capacity of the bladder - bladder doesn’t empty completely so not as much room for the incoming urine which the kidneys are also producing. This may feel like a small bladder, but the bladder is normal size but that capacity is inaccessible. These sorts of symptoms are called ‘voiding’ in nature and can be anticipated by narrowing of the pipe by the prostate. The bladder will compensate for this obstruction - to a degree and often temporarily.

    Urinary Urgency and Incontinence: The bladder may respond to obstruction by becoming spastic and making it difficult to postpone urination if the urge comes on (urinary urgency). In some cases men may experience a severe urge to urinate and start to leak before reaching the toilet. This sort of overactive bladder type symptom is typically in response to long standing obstruction. See the Special Circumstances section below.

    Bladder remodeling: The bladder is not quite the same as a motor despite the analogy that was used. Bladders are dynamic and can ‘remodel’ and adapt to obstruction - at least to some degree. Therefore, the bladder may compensate but also produce some symptoms reflective of remodeling of the bladder which may include a frequent desire to void, inability to put off urinating (urgency), leakage of urine (incontinence).

    In cases of severe obstruction, the bladder may ‘remodel’. This can take a couple of forms including thickening of the muscle (i.e. detrusor hypertrophy or trabeculation - think weight lifting for the bladder), increased sensitivity to filling (overactivity) and in the most severe cases replacement of muscle with non-contractile scar tissue (detrusor fibrosis or scarring which may result in a hypocontractile/atonic bladder). The most serious complication is detrusor fibrosis since it cannot be undone results in permanent pump failure. Patients must decide on living with a urethral catheter for the rest of their lives or emptying the bladder several times a day by inserting a tube into the penis (self-catheterization).

  • It is important to recognize that the lower urinary tract may not tell its owner (the patient) that it is having problems until the condition becomes severe or even life-threatening.

    While most men present with urinary symptoms, sometimes the effects of BPH may be insidious and barely noticeable because they develop slowly or do not produce symptoms until the condition is far advanced. Just like a man may feel fine until the moment they have a heart attack, a man with severe BPH may not recognize that a serious problem is happening until a severe complication has occurred. These include following:

    1. Urinary retention. Retention of urine occurs whenever one is unable to pass their urine and is retained in the bladder. It may lead to kidney failure. Urinary retention may be acute (sudden onset and usually painful) or chronic (often painless, sometimes with incontinence and urinary frequency). The former is easy to detect since men present with pain but chronic urinary retention may be insidious and can be more dangerous. Both usually require surgery but the additional issue with chronic retention is that loss of bladder strength is more common - see below.

    2. Kidney failure: Urine may back up to the kidneys and the back pressure may cause failure. May not cause any symptoms until over 80-90% of kidney function is lost. Metabolic abnormalities can be life-threatening and may be irreversible.

    3. Loss of bladder function and strength: The bladder may remodel in response to chronic obstruction. These changes may go unrecognized (and can be difficult to quantify with testing). One presentation is the atonic or hypocontractile bladder that has burnt out. The bladder looses its ability to contract and expel the urine. Basically the pump is broken. Patients may require life long use of a catheter and drainage bag or do life-long clean intermittent self-catheterization inserting a catheter in the bladder several times a day. There is no medication or surgery that can restore strength to the bladder. Another name for this is detrusor underactivity.

    4. Overactive bladder: The bladder may respond to obstruction by becoming spastic and overly sensitive to filling. Urinary frequency and urgency may result. The longer that obstruction is present, the less likely it is that these symptoms will improve even with surgery. Another name for this is detrusor overactivity.

    5. Urinary tract infections.: Inability to empty the bladder will predispose to infections of the urinary tract. Infections may involve the bladder, prostate or kidneys. In the most severe cases life-threatening urosepsis or septic shock can occur when bacteria enter the blood stream.

    Fortunately, a basic evaluation will typically capture most of the serious complications. Urinary frequency (day and night), leakage of urine (incontinence), straining to void, start-stop urination or any blood in the urine are indications to evaluate further. This may include cystoscopy, imaging or urodynamics.

    Most men who have suffered a severe complication require surgery.

Diagnosis and Evaluation

The diagnoses of BPH involves assessing urinary symptoms, physical examination and investigations. The goal is to determine the nature and severity of the condition and to assess for other causes.

  • Assessing urinary symptoms is aided by the use of questionnaires which provide a snapshot of they types and severity of symptoms from the disease. The International Prostate Symptom Score (IPSS) is a well-recognized clinical tool which can be used for diagnosis and treatment of men with BPH. It is also known as the AUA symptom score (AUASS). We recommend that all men coming for evaluation complete this questionnaire in advance.

    Men who have urinary frequency or need to void frequently at night are advised to complete a voiding diary.

    The degree of bother is critical in deciding if and how to treat this condition. Patients should consider which of their symptoms is the most distressing and if they would be willing to consider treatment with medication or surgery.

    It is important to note that serious complications may occur with minimal or no urinary symptoms. In many cases, the onset of symptoms may be so slow as to be imperceptible to the patient.

    Any history of urinary tract infections, blood in the urine, incontinence or pain are ‘red flags’ that merit additional testing.

  • The exam is directed to assess the general well being of the patient and focused on assessing the prostate itself and any signs of a complication from BPH.

    The size of the prostate is important in determining what treatments might be most effective and also to help with prostate cancer screening.

    A large prostate is not necessary to have symptoms from BPH just as a small prostate does not preclude severe obstruction.

  • Some testing is always necessary. In some cases, more detailed testing is necessary. The following tests may be performed:

    • Urine analysis: this is done in everyone. Checks for the presence of urinary tract infection and blood in the urine.

    • PSA: routine screening test for prostate cancer which also helps predict response to BPH treatment and risk of progression. Prostate cancer does not commonly present with symptoms - the most common presentation is an elevated PSA.

    • Creatinine: optional test to check for kidney function.

    • Cystoscopy: optional but very useful test. Cystoscopy uses a camera to assess the underlying anatomy - the ‘pump’ (bladder) and the ‘pipe’ (urethra, including the prostate). It can show the configuration of the prostate which helps determine the risks of progression and responsiveness to medication. It can determine what types medication might work best and if surgery is technically feasible. Cystoscopy can also evaluate how well the bladder empties. Cystoscopy is often performed if a patient is not responding to medication. It is a quick test taking just a few minutes and is usually well tolerated.

    • Ultrasound: optional imaging test which can be used to check for residual urine, backup of urine to the kidneys and to assess or prostate size.

    • Urodynamics: provides functional information on lower urinary tract function. It may be as simple as measuring a flow rate and a residual urine non-invasively by ultrasound or by measuring pressures, flows and sensation with the use of pressure transducers. It is complementary to cystoscopy which evaluates the anatomy.

Treatment

Urinary symptoms are common with advancing age. When to treat is often a personal and subjective matter with some exceptions.

By the time a patient comes for assessment by a urologist with BPH-LUTS the should have had a trial of medication. If not, we will generally start with an alpha blocker such as Flomax or Rapaflo. 5-ARI’s have much slower onset of action so this class of drug may not be used as first line therapy.

Surgery is necessary if a patient has developed a serious complication from BPH. Things such as renal failure, urinary retention or recurrent urinary tract infections can be life-threatening. A common presentation is the combination of urinary retention with renal failure (also known as an ‘acute kidney injury’). In such circumstances (and unless there is some reversible cause) patients are left with the prospect of a life-long catheter or having surgery. Patients almost always choose surgery unless there is some reason why they are not a candidate for surgery. An important part of the evaluation is to check if a complication is present or is likely to develop in the future.

In all other circumstances, the decision to treat is based on how bothersome one’s symptoms are and also considers the possible benefit of medications to reduce the risk of progressive BPH. The degree of ‘bother’ that urinary symptoms cause is highly subjective and personal. If a patient finds themselves scheduling their lives around the need to urinate or finds that they are tied to the toilet, it’s time to explore ones options.

  • General measures can be surprisingly effecting in helping with urinary symptoms. Some symptoms are helped better than other and it should be recognized that lifestyle changes do take some time to work.

    There is good evidence to support the following interventions: 

    • Exercise and weight loss. This affects both the nervous system and the hormones in the body.

    • Low-fat, high vegetable diet. Especially vegetables that are intensely colored or dark as they contain high levels of lycopenes. Lycopenes are anti-oxidants which reduce prostate inflammation.

    • Good sleep hygeine. This is important for patients with frequent urination at night.

    • Pelvic floor muscle exercises. For men with urinary urgency and frequency.

    • Avoidance of bladder irritants such as caffeine or alcohol may help with urinary frequency during the day or at night.

    • Treatment of constipation.

    These maneuvers are helpful to a point. They are not going to provide meaningful benefit to the man who is in urinary retention or with another serious complication of BPH - those men need surgery.

  • Watchful waiting is a strategy in which the men who have BPH are essentially observed. Men can make lifestyle and dietary modifications. The best candidates for watchful waiting meet the following criteria:

    1. They have not developed a complication from BPH and are at low risk of developing one in the future.

    2. Their symptoms are mild and minimally or non- bothersome. Note that one’s perception of ‘bother’ is different than how severe one’s symptoms are. For example, a man may find urinary incontinence minimally bothersome and manageable with the use of a diaper but the presence of overflow incontinence is a serious symptom none the less.

    In well-selected men, about 4 in 5 patients will not see any progression in symptoms over the following 5 years.

  • There are several types of medications used to treat BPH. They may be used individually or together. Response to each type of medication will depend on the particular circumstances.

    These medications are meant to be taken long term - they are not ‘cures’ in the sense that taking the medication for a short duration will remedy the problem in the same way that taking an antibiotic will cure an infection. The goals of medications are to alleviate symptoms and to prevent the development of disease progression or complications.

    There are 2 general targets for medication:

    1. Prostatic obstruction: alpha blockers, 5-alpha reductase inhibitors and PDE5 inhibitors all aim to reduce obstruction.

    2. Overactive bladder: bladder antispasmodics aim to reduce urinary frequency and urgency when these are not due to retention of urine.

    The classes of BPH medications are discussed below and include:

    1. Alpha-blockers. The relax the muscle component of the prostate allowing the urine to pass through more easily.

    2. 5-Alpha-Reductase Inhibitors (5ARIs). These shrink the prostate by about 20% and open the lumen allowing urine to pass through more easily.

    3. Phosphodiesterase 5 Inhibitors (PDE5 inhibitors). These are the same medications used to treat erectile dysfunction. Low dose tadalafil (Cialis) is approved for use but not typically covered by insurance.

    4. Bladder antispasmodics. These medications can be useful to treat urinary urgency and frequency when those symptoms are not the result of incomplete emptying. Anticholinergic medications and beta-3 agonists are the 2 primary classes.

    Medications have a limited role in men who have developed a serious complication from BPH. In some circumstances, men may cautiously try these medications under supervision but most men need surgery. There are risks in postponing surgery when it is needed.

  • Visit the page on TURP for BPH. Surgery generally undertaken for 2 primary reasons.

    1. Symptoms are the most common reason why men have surgery. Medications may not be effective enough to obtain the degree of symptom relief that a patient needs or desires. Sometimes the side effects or prospect of taking medication long term is unattractive. Men who have surgery do not need to continue taking BPH medications.

    2. Complications from BPH may necessitate surgery. Patients who experience urinary retention, recurrent infections or bleeding from BPH will often have no other option than to have surgery. Patients may rarely decide to live with a long term urethral catheter or perform self-catheterization but these options are uncomfortable and come with their own set of risks.

  • Minimally invasive surgical procedures (MISTs) are increasingly becoming a treatment option in a select group of men with BPH-related symptoms.

    TURP (and other techniques which remove prostate tissue) has long been considered the ‘gold-standard’ for treatment of BPH and is the treatment of choice once a complication has arisen. However, MISTs are targeted at the group of men in whom long-term medications are not particularly attractive and who seek procedures with reduced up-front recovery costs as compared to TURP. Some of the MISTs are associated with reduced sexual dysfunction, especially in respect to ejaculation.

    The major concern regarding MISTs have to do with durability (how long the beneficial effects last), the true complication rates (which often only become apparent when in broad clinical use) and the magnitude of benefit (measured not just symptomatically, but also functionally as measured with urodynamics).

    There is a role for such treatments in men who don’t absolutely need a TURP and this is an area of active investigation.

    Read more below.

  • There are numerous supplements, vitamins and herbs which have been marketed to enhance 'prostate health'. In almost all circumstances, either no benefit or harm has been demonstrated in scientific studies looking at these kinds of interventions - claims by those selling those medications notwithstanding. Here is a list of things which can be safely ignored or should be avoided:

    • Vitamins, especially vitamin E. The large scale SELECT trial demonstrated a significant increase in the risk of developing prostate cancer. The higher the dose of vitamin E, the higher the risk, especially for high-grade tumors.

    • Zinc. Seems to be associated with an increased risk of developing a complication from BPH and developing prostate cancer.

    • Anti-oxidants (e.g. lycopene). For unknown reasons, antioxidants packaged in pill form do not provide benefit, whereas those ingested in foods do help.

    • Saw-Palmetto. There have been 2 very well designed randomized trials looking at the effect of saw-palmetto published in 2003 and then in 2011. Neither demonstrated any benefit in symptoms. That men do describe relief of symptoms is a testament to the placebo effect and the fact that urinary symptoms can improve on their own. Having said that, side-effects are very, very rare so feel free to try saw palmetto.

    The bottom line is that pill are not a substitute for a health diet and exercise.

Medications

Physical obstruction of the outflow path from the bladder plays a significant role in urinary symptoms (though this is an over-simplification). The prostate surrounds the urethra. The bladder may remodel in response to chronic obstruction resulting in urinary urgency and frequency. Medications aim to address these 2 separate problems and thereby alleviate symptoms and reduce the risk of developing a complication.

Alpha-1 Blockers: Flomax, Rapaflo, Hytrin, Cardura

First line treatment in all men with BPH.

This class of medication relaxes the smooth muscle in the prostate and at the bladder neck. Smooth muscle is one of the 3 muscle types in the body - the others being skeletal and cardiac muscle. Smooth muscle is found in blood vessels and viscera (e.g. bowels) which explains some of the side-effects such as dizziness and fainting.

They tend to have a quick onset of action, often within hours to days, and are all roughly equally effective at adequate doses (some of these medications require dose titration). Maximal effects usually take a few weeks. They do not reduce the long term risk of BPH-related complications and are only indicated for relief of symptoms.

  • Alpha blockers can be used in any man with bothersome BPH symptoms. They are considered first-line drug treatment for BPH.

    • They are less effective in men with larger prostates.

    • They have rapid onset of action so can be used for ‘trials of void’ after a man has gone into urinary retention. 5 ARIs take months to shrink the prostate and are never of any immediate benefit.

    • They tend to be well tolerated on a long term basis. Their effectiveness is usually sustained for long periods of time.

  • All of the alpha blockers are equally efficacious. However, they do differ a little in terms of side-effects and convenience.

    • Uroselective alpha 1A blockers.

      • Tamsulosin (Flomax) 0.4 mg daily

      • Silodosin (Rapaflo) 8 mg daily

      • Alfuzosin (Uroxatral) 10 mg daily

      • All come as a single dose and do NOT require dose titration. This makes them more convenient. They also tend to have less dizziness with silodosin having the least dizziness of the group.

    • Regular alpha 1 blockers. require dose titration. However, they may be more effective than alpha 1A blockers in treating urinary urgency and frequency and less likely to cause ejaculatory dysfunction.

      • Terazosin (Hytrin): 1-20 mg daily

      • Doxazosin (Cardura). 1-10 mg daily

  • All medications carry risks of side-effects. Alpha blockers have a low rate and severity of adverse events. While most men tolerate this class of medication well, side-effects may occur including but not limited to the following:

    • Dizziness or fainting (orthostatic hypoptention). Less common with silodosin (Rapaflo).

    • Weakness and fatigue.

    • Nasal congestion.

    • Reduced ejaculatory volume or loss of ejaculation. This seems to be worse with the super-selective alpha blockers (tamsulosin and silodosin) compared to the selective alpha blockers (doxazosin and terazoson).

    • May affect cataract surgery. Inform your ophthalmologist if you are taking this class of medication. May be worse for Flomax. Alpha blockers do NOT affect vision directly.

  • General tips for getting the most out of this medication and minimizing the risk of side-effects.

    1. Stop the medication if you have not noticed any benefit or think you are having a serious side-effect such as dizziness. Check with your physician before doing this if possible.

    2. Take before bed. The best time is usually in the evening. This will reduce the impact of light-headedness.

    3. Avoid dehydration. Being 'dry' will exacerbate any dizziness.

    4. Dose titration. Some medications require gradual upward dose adjustment. If you are not experiencing any relief of symptoms, ask your doctor if you are on a high enough dose.

      1. Hytrin (terazosin): maximum dose is between 10-20 mg daily

      2. Cardura (doxazosin): maximum dose is 8 mg daily

5-alpha Reductase Inhibitors: Proscar, Avodart

First line treatment in men with enlarged prostate and/or higher PSA levels (these tend to go hand in hand).

This class of medications shrinks the prostate by reducing the production of dihydrotestosterone (but leaving testosterone levels unchanged). While one might think that making the prostate smaller might tighten the urethra, the reduction in size actually opens the lumen. The reduction in size is modest - usually about 25%.

They have a delayed onset of action, typically taking 6 months before any benefit is seen so a longer term commitment is required. With the exception of sexual dysfunction, 5ARIs are very well tolerated and rarely have any interaction with other drugs.

  • The bigger the prostate, the more effective this class of medications is. They typically reduce prostate volume by about 25% - therefore, a man with a 20 gram prostate might see a 5 gram reduction in size (which is a small change) but a man with a 100 gram prostate will see a 25 gram reduction (a large change).

    A valuable property of 5 ARIs is that they are able to favorably change the trajectory of BPH - not just help whatever symptoms might be present. 5 ARIs reduce the risk of symptom progress and the development of complications from BPH. The absolute magnitude of benefit is limited if the predicted risk is low, but in those men who are at increased risk of developing a complication (e.g. very large prostate or incomplete emptying) 5ARIs can reduce the risk of needing surgery or developing urinary retention substantially. Alpha blockers do not change the course of the disease. There is a tradeoff in regards to side-effects and also because a long-term commitment is necessary. Also, if a man has already developed a serious complication they should probably go for surgery as the time for prevention has already passed.

    5 ARIs are more beneficial in men with prostate sizes >30-40 grams or so. Prostate size can be estimated on exam, on imaging or with cystoscopy.

    Men with large prostates often have higher PSA levels. Men with PSA levels greater than 1.5-2 mcg/L are more likely to benefit - this ends up being most of the patients who are referred to a urologist.

    One specific use of 5ARIs is to reduce the risk of recurrent bleeding from the prostate. This is an ‘off-label’ use but clinical studies show a roughly 50% reduction in the risk of recurrent bleeding. Because of the delayed onset of action, 5 ARI’s are not useful when acute bleeding is occurring.

  • There are only 2 medications in this class and both are equally effective. Dutasteride (Avodart) has a slightly faster onset of action than finasteride (Proscar) which may be of benefit in a small number of men.

    Finasteride 5 mg daily (Proscar).

    Dutasteride 0.5 mg daily (Avodart).

  • 5 ARIs tend to be well tolerated with one exception - sexual dysfunction. If a man is not sexually active or sexual function is unimportant, 5 ARIs are a great choice. They rarely interact with other medications.

    Sexual dysfunction occurs in about 1 in 4 patients who take 5 ARI’s long term. Sexual side effects include:

    • Reduced sex drive (libido). This is the most common side-effect.

    • Reduced ejaculatory volume.

    • Erectile dysfunction. Occurs in about 5%.

    These side-effects take months to resolve after discontinuation of the medication and may be permanent in a small number.

    Breast tenderness or enlargement occurs in 1-2% of patients.

    Two studies have suggested that 5 ARIs are associated with a higher incidence of high-grade prostate cancers but a causal effect has not been proven. This controversial side-effect has largely been put to rest.

    DOI:10.1097/MOU.0000000000000464

    DOI: 10.1158/1055-9965.EPI-21-1234

    DOI: 10.1158/1055-9965.EPI-22-0338

    Women of child-bearing age should avoid contact with the medication as it has the potential to cause congenital defects related to sexual development.

  • DON’T STOP IF YOU DON’T IMMEDIATELY NOTICE ANY CHANGES! A minimum 6 month trial is necessary to assess effectiveness.

    If the medication is being taken for prevention, it should be continued even if there is no improvement in symptoms.

Phosphodiesterase 5 Inhibitors: Cialis

Phosphodieseterase 5 inhibitors (PDE5Is) are best known for their beneficial effects on erections - Viagra and Cialis are PDE5Is. Cialis (tadalafil) at the 5 mg daily dose is the only on approved for use in BPH. It is thought to act as a smooth muscle relaxant, similar to alpha blockers, but also to have other mechanisms of action.

In general, PDE5Is have a modest effect on symptoms but minimal to no effect on improving flow rates. In addition, studies had only limited follow-up of less than one year. For these reasons, PDE5Is gained little traction for use in BPH. Limited coverage by extended health and no coverage by Pharmacare (in BC) limited used. Having said that, they tend to be well tolerated and because of the beneficial effects on erections are a reasonable option in men. They are not considered first line treatment.

  • PDE5Is seem to be most effective in younger males who also happen to be slimmer (having a lower BMI).

    They may be used in combination with alpha blockers and 5 ARIs.

    It is unknown what differences, if any, exist in the response based on patient characteristics (e.g. prostate size, PSA, etc.).

  • The only PDE5I licensed for use in BPH is tadalafil (Cialis) 5 mg daily.

    Neither sildenafil (Viagra) or vardenafil (Levitra) have been licensed.

  • Side effects of low-dose Cialis are generally limited to flushing, reflux/dyspepsia, headache, back pain and nasal congestion These are relatively uncommon at the dose used for BPH.

    It should not be used if certain types of cardiovascular disease are present, including:

    • Unstable angina.

    • Uncontrolled arrhythmias (palpitations).

    • Low blood pressure.

    • Uncontrolled high blood pressure.

    • Recent history of stroke.

    • Certain visual abnormalities (ischemic optic neuropathy).

Combination Therapies

The most common combination therapy is combined use of an alpha blocker plus a 5-alpha reductase inhibitor (e.g. Flomax + Proscar). The have different mechanisms of action and the use of these 2 different medications works better than either used on its own. The combined strategy is best utilized in men who are likely to benefit from a 5ARI.

A commonly used strategy is to use combination therapy for 6-12 months and then do a trial where the alpha blocker is stopped. If there is no deterioration in urinary symptoms then the patient may continue on the 5 ARI alone, thereby reducing their medication burden. Patients who start with very large prostates or more severe symptoms are likely to do better continuing both medications long-term.

Jalyn is a combination of dutasteride 0.5 mg + tamsulosin 0.4 mg in a single pill.

Bladder Relaxants

This class of medications can be added to alpha-blockers or 5-ARI's to address 'storage' urinary symptoms (urgency, frequency, nocturia). Typically added only if alpha-blockers do not adequately address urinary symptoms. Specific side-effects include dry-mouth, dry-eyes and constipation. See treatment for over active bladder.

The 2 major classes are anti-cholinergic medications and beta 3 agonists.

Surgery

Review the section on Transurethral Resection of the Prostate (TURP) for more detail.

Surgery is most commonly used when medications fail to provide the desired effects and the symptoms of BPH are moderate to severe. In these men, surgery can usually provide excellent symptom relief. The symptomatic benefit from surgery is a magnitude greater than that from medication, but surgery does come with additional risk. A trial of medication is reasonable in men without complications from BPH and those at low risk for progression.

The other major reason for surgery is when a man experiences a serious complication from BPH such as urinary retention, kidney failure, recurrent bleeding or infection.

There are several different surgical approaches to managing BPH, but the basic goal is enlarge the urinary channel that passes through the prostate (the prostatic urethra). There are multiple different types of surgery for BPH and there is no single best surgical approach.

The approaches to prostate surgery for BPH include:

  1. Resection;

  2. Enucleation;

  3. Vaporization;

  4. Alternative ablative techniques; and

  5. Non-ablative techniques.

Bipolar or monopolar TURP is the current standard surgical procedure for men with enlarged prostates and bothersome moderate-to-severe LUTS secondary to benign prostatic obstruction.

 

Other Treatments

There is always ongoing investigation into novel treatments for BPH. This is a good thing - to advance the treatment of a common condition.

All treatments have some risk. Any treatment that purports to be risk-free is lying. Established treatments have better defined risks and benefits, especially over the long-run.. Established treatments will also have stood the test of time and have had the time to become optimized for benefit and to reduce the risks. It is generally best to wait until a treatment modality has undergone enough investigation to ensure it is both safe and effective.

In the short run, the BPH market for treatments is a voting machine but in the long run it is a weighing machine (to adapt a quote from Ben Graham regarding the stock market). Some of the treatments listed below will eventually become a routine part of the armamentarium of BPH treatments whereas many will end up in the history books with other failed BPH treatments. Google search does not prioritize quality of treatments - it prioritizes by popularity and by paid-for ads. Buyer beware.

Considerations When Undergoing New or Investigational Treatments

Patients interested in novel or investigational treatments are well advised to only undertake such treatment under the umbrella of a well-administered clinical trial which has appropriate oversight and where the financial incentives of those administering the trial are not in conflict with their own interests.

Anyone considering an investigational treatment should be counselled and consented appropriately both in regards to known risks as well as potential risks associated with the intervention and alternatives. This includes review of established treatments. Informed consent regarding the investigational nature of the intervention is the current medicolegal and ethical standard. We encourage participation in clinical trials when patients understand the purpose, risks and benefits of those trials.

The Canadian Journal of Surgery comments on obtaining consent for clinical trials.

The Royal College of Physicians and Surgeons discuss consent for clinical trials.

  • This approach essentially ‘steam cooks’ prostate the central component of the prostate resulting in subsequent shrinkage of the treated area. The loss of prostate volume widens the urethral lumen resulting in symptom relief.

    The procedure is done through a cystoscope and needles are injected into the prostate delivering heated water vapor. Anesthetic options include local/sedation, spinal anesthetic or general anesthetic. It is done as a daycare surgery. The procedure takes less than 30 minutes and patients will generally have a catheter for about 2-3 days.

    Risks include burning with urination blood in the urine, blood in the ejaculate, urinary frequency and urinary retention, urinary infection, reduced ejaculatory volume. Retreatment rates are about 5% over 5 years. Median lobes can also be treated.

    While it is important to note that there are limitations (prostate <80 cc), that the results are surprisingly durable.

    References:

    https://doi.org/10.1097/JU.0000000000001778

  • PAE involves the embolization of the blood vessels which supply the prostate. This is essentially cutting off the blood supply to the prostate by the injection of material that lodges within the arterial inflow. The intent of embolization is to produce necrosis of the prostate (tissue death) and a decrease in the size of the prostate. The hypothesis behind the procedure is that it will reduce obstruction. PAE is done by an interventional radiologist - a specialist whose focus is on body imaging and interventional approaches that rely heavily on imaging techniques for guidance. Radiologists do not have training in the diagnosis nor management of BPH but are solely focused as technicians to perform this procedure.

    The major professional organizational guidelines have assessed all of the currently available evidence on PAE. The most recent guidelines on the management of BPH include the  American Urological Association BPH Guidelines , European Association of Urology Guidelines, and 2018 Canadian Urological Association Guidelines. You can link to these guidelines to review the full text. All of these organizations recognize PAE as investigational and that its use should be restricted to a clinical trial.

    It is recommended that PAE studies be undertaken in concert with a urologist since a urologist is an expert in BPH and because in some cases surgical management of PAE-related complications has required surgical intervention or expertise.

    What follows are excerpts from the 2019 guidelines  to place the role PAE into perspective.

    From the AUA 2018 BPH Guidelines Discussion on PAE (Expert Opinion): "PAE is a newer, largely unproven MIST for BPH. High level evidence remains sparse, and the overall quality of the studies is uniformly low. Some of the deficiencies of the included trials include 1. A lack of randomization, 2. High levels of susceptibility to selection, detection, attrition, and reporting biases, 3. The common inclusion of a preoperative status of urinary retention, and 4. The absence of standard inclusion/exclusion criteria for a LUTS/BPH RCT. ... Given the heterogeneity in the literature—and concerns regarding radiation exposure, post-embolization syndrome, vascular access, technical feasibility, and quality control at lower volume centers—it is the opinion of the Panel that PAE should only be performed in the context of a clinical trial until sufficient evidence from rigorously performed studies is available to indicate definitive clinical benefit. The Panel recommends trials involve multi-disciplinary teams of urologists and radiologists; and that, as with other MIST therapies, RCTs comparing PAE to sham be considered to account for significant placebo effects."

    From the CUA 2018 BPH Guidelines: "We recommend that PAE should not be offered at this time for the treatment of LUTS due to BPH (conditional recommendation based on moderate-quality evidence)."

    From the EAU 2019 Guidelines regarding PAE: Section on 'Techniques Under Investigation'

    • Practical considerations: The selection of LUTS patients who will benefit from PAE still needs to be defined. Prostatic artery embolization is a technically demanding procedure that can be performed by interventional radiologists with the necessary experience and additional training. It is important to stress, that PAE impacts the entire prostate without the option for focused and controlled action on BOO. This may explain the higher clinical failure rate compared to reference methods like TURP and commonly observed complications like AUR. A multidisciplinary team approach of urologists and radiologists is mandatory as the basis for future RCTs of good quality with long-term follow-up in order to integrate this treatment option into the spectrum of efficient minimally invasive treatment options.

    • Adverse events after PAE can include both side effects and complications. Most complications were described as minor; however, a few major complications were reported including one incidence of non-target embolization of the bladder wall that required surgical intervention. The SR of the comparative studies showed that PAE resulted in more adverse events than TURP/OP (41.6% vs 30.4%, p=0.044). Interestingly, the frequency of AUR after the procedures was significantly higher in the PAE group (9.4% vs 2.0%, p=0.006)

    From Tarun et al. British Journal of Urology Int (2018; 122: 167-168). Commentary from two advocates of PAE.

    "Our overall experience is now in excess of 200 cases and we are aware that some patients will do well, others less well. … Level 1 evidence is of course a fundamental requirement for a change in definitive practice … Perhaps the real challenge highlighted by the ROPE study is that the time has come to consider a randomized controlled trial of prostate embolization vs early non-surgical treatment of BPH (short title ‘PREVENT-BPH’), with randomization to PAE or either a-blockers and/or 5-a-reductase inhibitors or placebo."

    Comment: there is no comparative TURP group in this study. These two advocates of the procedure are cautiously optimistic.

    From Tomas Griebling MD, MPH. Journal of Urology 2018 in Commentary on Want et al. PAE for the treatment of BPH in Men greater than 75 years: a prospective single-center study: "Additional prospective clinical studies, including head-to-head trials comparing prostatic artery embolization to other minimally invasive surgical options, are needed. Such studies will help better identify the role of this procedure as well as ideal candidates, and will allow direct comparison of risks, benefits and clinical outcomes. 

    There are other serious complications that are exclusive to PAE and which are not seen elsewhere including penile glans necrosis - having the tip of the penis become injured by ‘non-target’ injury to the blood vessels feeding the head of the penis. The consequences include need or additional treatment and recovery (e.g. hyperbaric oxygen) with long term complications of erectile dysfunction, numbness of the head of the penis and potentially cosmetic issues by permanent tissue loss and scarring. A single center reported 6 such injuries over 2 years. Considering that PAE is an infrequently performed procedure and that complications often go unreported, this sort of publication should highlight the risks of what is sometimes described as a ‘minimally invasive procedure’. DOI: 10.5534/wjmh.210244

    There are multiple reasons why PAE is considered investigational. Some of these are detailed above. Reliable data (multicenter, randomized, controlled trials, satisfactory follow-up with accounting of secondary procedures and major complications, rigorous outcomes analysis) are necessary before drawing any conclusion about PAE. Until such time as there is such data, the consensus amongst experts in the field as of 2019 is that PAE is currently considered investigational. This recommendation subject to change based on additional data. 

  • This is an interesting approach to obstruction. It is basically a prostatic stent to hold open the prostatic fossa. Fairly straight forward to place, far better at preserving ejaculation than most surgical approaches. Having said that, it is still early days for this approach and the data are limited. It does not seem to be as effective as TURP and there are a few complications that are not seen with TURP (e.g. stone formation). Is it reasonable to try this? Maybe - if you can accept that you might not get as good a result and that you might need to have repeated procedures every few years.

  • Dilation (stretching) of the prostatic urethra has a somewhat checkered past in the history of BPH management. Short term results of virtually all new and novel approaches to BPH treatments are often favorable - many times because of placebo effect but sometimes because the treatment actually made a difference. Balloon dilation of the prostate was ultimately abandoned because it did not produce durable results.

    Balloon dilation is making a comeback with an important modification: the use of paclitaxel (impregnated into the balloon itself and transferred to the prostate tissue with deployment) with the intent of preserving the mechanical gains of the dilation and splitting of the anterior commissure by inhibiting healing within the prostate tissue. Basically ‘splitting the prostatic urethra and limit healing’ to maintain any gains in the size of the lumen.

    The FDA approved this device in 2023. The early results are promising albeit in a relatively small number of patients and with short term follow-up (1 year). A maximum prostate size of 80 grams has been accepted however most patients undergoing Optilume BPH have a prostate in the 40-50 gram range. As with any prostate procedure there are risks including: bleeding, urethral injury, infection and incontinence. Many of these complications are temporary. Loss of ejaculation is rare but occurs in about 1 in 20 patients. Patients require a catheter for 2-3 days after surgery and procedural pain management is with general anesthetic or procedural sedation combined with local anesthetic.

    Every approach to treatment of prostate disease comes with some compromise. How a treatment performs in the real world usually takes years of experience in thousands of patients to become apparent.

    DOI: /UU.000000000000356