Benign Prostatic Hyperplasia

Background

 

Benign prostatic hyperplasia (BPH) is one of the most common conditions affecting the prostate. There are multiple terms which had been used to described this condition which include benign prostatic enlargement (BPE) and prostatism. Technically speaking, BPH is a histologic diagnosis which means that the diagnosis is made from a sample of tissue. Practically speaking, however, BPH is diagnosed when a man presents with a constellation of symptoms suggestive of the condition, even in the absence of a prostate which feels enlarged on rectal examination.

 

BPH increases with age and is found in approximately a 50% of men at age 60 and 90% at age 85 many 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 from narrowing of the prostatic urethra - that is, the pipe becomes too tight. this results from enlargement of the prostate gland which compresses the pipe as well as an increase in the muscular "tone" of the prostate. In reality, this is an over-simplification. While obstruction is still recognized as a major component, it is increasingly recognized that changes within the bladder itself are responsible for many of the urinary symptoms resulting from BPH.

 

Diagnosis & Evaulation

 

The diagnoses of BPH involves assessing urinary symptoms, physical examination and in some cases basic testing such as urine analysis. In select cases, additional testing such as flexible cystoscopy or urodynamics may be required. BPH can rarely cause serious adverse effects and excluding these is important - as is excluding the presence of prostate cancer. The most serious adverse effects from BPH include:

 

  1. Urinary retention - inability to pass urine
  2. Recurrent bladder infection
  3. Hematuria - blood in the urine
  4. Bladder stones

 

Symptoms from BPH can include urinary hesitancy (the stream is slow to start), a slow urinary stream, the requirement for abdominal straining to empty the bladder, a stream which is intermittent (starts and stops), sensation of incomplete emptying. Men can also have frequent urination (both day and night) and occasionally urinary incontinence (leakage).

 

In the absence of a serious adverse effect from BPH, the most critical thing is determining how bothered a patient is by their symptoms. The International Prostate Symptom Score (IPSS) is a well-recognized clinical tool which can be used for diagnosis and treatment of men with BPH. this questionnaire is also known as the AUA symptom score (AUASS). We recommend that all men coming for evaluation fill out this questionnaire in advance.

 

Prostate exam is an important part of the evaluation of men with BPH-related symptoms. is, however, very important to note that the absence of enlargement on prostate examination in individual patient is not exclude the presence of BPH. What this means is that even men with small prostates can have BPH-related symptoms and conversely, man with large prostates may not have any symptoms whatsoever. Two major reasons why a prostate exam is performed include:

 

  1. Prostate cancer risk assessment. The finding of a nodule or a firm area can be suggested of prostate cancer and a biopsy may be recommended.
  2. Assess size. Larger prostates may benefit from medications to shrink them, where a smaller prostates will not. In addition, surgical approaches to management of BPH, if they become necessary, may vary based on prostate size.

 

Treatment

 

With rare exception*, the over riding factor that drives treatment is how much the symptoms are BOTHERING you. Only you can answer this. As a consequence, you are in the drivers seat. Your urologist will provide you on advice as to what treatments are likely to fit your individual circumstances, but IT IS ENTIRELY UP TO YOU IF YOU WANT TO CONTINUE WITH TREATMENT. Basically, if you don't feel that the treatment is helping, you probably don't need to continue. There are exceptions to these guidelines, so be sure to ask if you are unsure why your urologist has made specific recommendations. 

 

* Situations where treatment is either strongly recommended or must be undertaken:

  1. Urinary retention: you are unable to empty the bladder at all or are retaining a substantial amount of urine. Most men can empty to completion (less than about 50 mL/1-2 ounces). Some men may retain some urine but it is unusual and unhealthy to have more than 200-300 mL in the baldder after urination. You may not be able to tell how much you are retaining and for this reason we may measure the 'Post Void Residual' (PVR) with a bladder scanner or at cystoscopy
    1. If you have required a catheter to drain the bladder and there is nothing that can be identified as precipitating the episode of retention that is reversible, there is a very, very high chance that you will require surgery. Even if you are able to urinate after removal of the catheter, the majority of men will require surgery within 2 years of the episode (up to 8 in 10 men in some studies. You may want to proceed with surgery.
    2. Just because you are urinating does not mean you are not retaining a substantial amount of urine. Some men have 'Overflow' incontinence. In this type of incontinence, a man will need to urinate very frequently or have urinary leakage because the bladder if filled to capacity. The kidneys continue to push more urine into the bladder and it will often leak out, just as an over full sink will overflow if the fawcet is left on when the drain is plugged. Often associated with kidney problems. Surgery highly recommended.
  2. Kidney failure from BPH: this is almost always associated with urinary retention, sometimes with overflow incontinence. Surgery is the necessary treatment - post-postponing surgery can lead to kidney failure. Fortunately this is usually reversible.
  3. Recurrrent bleeding related to the prostate. Some medications (finasteride and dutasteride) may reduce the chances of bleeding. If you have had more than a few episodes, you should strongly consider surgery.
  4. Recurrent infection related to incomplete emptying. 

If you have any of these problems, medications are unlikely to do the trick and postponing surgery may lead to complications. The alternative to surgery in some of these circumstances it to have a catheter placed or to self-catheterize (put a tube in and out of the bladder through the penis several times a day) for the rest of your life. Most people find surgery much more attractive in these circumastances. Talk with your urologist.

 

What are the treatment options? There are 3 general classes of treatment. For the most severe cases, there is no substitute for surgery but in all other cases, less invasive approaches can be tried first.

 

General Measures Medication Surgery

Changes in behavior including fluid intake, urinary habits and dietary changes These are interventions that all men should try.

There are 3 general classes of medications used in BPH. The can be used individually or together, depending on the circumnstances.

  1. Alpha-blockers: prostate muscle relaxants
  2. 5-alpha-reductase inhibitors: shrink the prostate. E.g. finasteride (Proscar) or dutasteride (Avodart)
  3. Anticholinergics: bladder relaxants
There are a number of  surgical approaches to treating BPH. All have the basic goal of enlarging the outflow tract of the prostate.

 

General Measures

 

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:

 

  1. Exercise and weight loss. This affects both the nervous system and the hormones in the body.
  2. Low-fat diet
  3. High-vegetable diet. Especially those vegetables which are intensely colored or dark as they tend to contain high levels of lycopenes - a type of anti-oxidant which the human body is not capable of making on it's own.
  4. Good sleep hygeine. This is important for patients with frequent urination at night.
  5. Pelvic floor muscle exercises. For men with urinary urgency and frequency.

 

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:

 

  1. 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.
  2. Zinc. Seems to be associated with an increased risk of developing a complication from BPH and developing prostate cancer.
  3. Anti-oxidants (e.g. lycopene). For unknown reasons, antioxidants packaged in pill form do not provide benefit, whereas those ingested in foods do help.
  4. 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 there is no substitute for looking after yourself - both in terms of 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. Decresing muscular tone in the prostate and reducing it's size can help urinary symptoms.

 

  Alpha-Blockers 5-Alpha Reductase Inhibitors

When & How?

Relax the prostate muscle allowing it to 'open' better. Also has an impact on bladder sensation.

Useful in most men with symptoms.

Onset of action is almost immediate.

Does not prevent symptom progression or reduce the risk of needing surgery.

Gradually shrink the prostate. Reduces dihydrotestosterone levels, but do not reduce testosterone levels.

Usefulness increases with increasing prostate size.

Take at least 3-6 months

Reduce symptom progression and the risk of requiring surgery in the future (depends on the patient).

Cautions and side-effects

Dizziness

Nasal congestion

Reduced ejaulation volume

Can affect cataract surgery

Reduced ejaculatory volume

Breast tenderness

Medications

Flomax (tamsulosin)

Xatral (alfuzosin)

Hytrin (terazosin)

Cardura (doxazosin)

Jalyn (Avodart + Flomax)

Proscar (finasteride)

Avodart (dutasteride)

Jalyn (Avodart + Flomax)

 

Tips for Taking Alpha-blockers

  1. Take before bed. The best time is usually in the evening. This will reduce the impact of light-headedness.
  2. Avoid dehydration. Being 'dry' will exacerbate any dizziness
  3. 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 - the maximum dose is between 10-20 mg daily
    2. Cardura - the maximum dose is 8 mg daily
  4. 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.

 

Tips for Taking 5-Alpha Reductase Inhibitors

  1. Take them for a minimum of 6 months. These medications will not 'shrink' the prostate overnight and do take time to work. If you haven't noticed any improvement after 1-2 months, it may be because you havent taken them long enough
  2. PLAN ON MAKING A MINIMUM 6 MONTH COMMITMENT IF YOU TAKE THESE MEDICATIONS

 

IMPORTANT: Alpha blockers can have an effect on the eyes which can make cataract surgery more difficult. Alpha blockers do NOT affect vision, just cataract surgery. Ultimately, it is the eye doctor's responsibility to determine if there are any medications which might affect any surgery they hope to undertake with you. You can help them by letting them know which medications you are taking.

 

Anticholinergics

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

 

Surgery

 

When medications fail to provide the desired effects and the symptoms of BPH are severe enough, surgery can usually provide excellent symptom relief.

 

There are several different surgical approaches to managing BPH, but the basic goal is enlarge the urinary channel as it traverses the prostate. There is no single best approach.

 

Approach Comments

Intact removal

Removes actual prostate tissue (whole or with morcellation)

Examples: open simple prostatectomy, transurethral holmium laser enucleation (HoLEP) or transurethral resection of the prostate (TURP)

Vaporization

This coverts tissue to debris such that none is available for analysis.

Examples: laser vaporatization (e.g. Greenlight PVP), tranurethral holmium laser ablation of the prostate (HoLAP), contact laser prostatectomy (CLP), transurethral vaporiazation (electrical) of the prostate (TUVP)

Induction of necrosis with delayed reabsorption

Thes induces necrosis then the tissue using heat or cooling followed by a slow reabsorption or sloughing of tissue.

Example: transurethral needle ablation of the prostate (TUNA), transurethral microwave thermotherapy (TUMT)

Hybrid techniques

Combinations of the above

 

Things to consider include the size of the prostate, recovery time, durability of the results (i.e. chances of requiring repeat surgery), other complications (such as bleeding, pain). Your urologist will discuss these options with you.

 

Information on transurethral resection of the prostate can be found here.

 

Other Treatments

 

There is always ongoing investigation into novel treatmetns for BPH. Some have low risk such as phosphodiesterase-5 inhibitors (e.g. Cialis/tadalafil). Others have the potential for major harm. It is generally best to wait until a treatment modality has undergone enough investigation to ensure it is both safe and effective - and then waiting a little longer until it has been in broad clinical usage for a few years, especially for surgical interventions. This will allow time for the techniques to be optimized. The alternative is to enter a well-administered clinical trial which has appropriate oversight and where the financial incentives of those administering the trial are not in conflict with your own interests.

 

Prostatic Artery Embolization (PAE)

 

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 placement of material that lodges within the arterial inflow. The intent of embolization is to produce necrosis of the prostate (cell 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. 

 

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  2018 Americal Urological Association BPH Guidelines , 2019 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 embolisation 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 embolisation 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 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.

 

Prostatic Urethral Lift (Urolift)

 

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.

 

Considerations When Undergoing New or Investigational Treatments

 

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 has a commentary on obtaining consent for such trials.

The Royal College of Physicians and Surgeons discusses consent for trials.

 

 

On the Web

General Urology Websites

Canadian Urological Association  Extenstive library of downloadable pamphlets on a wide range of urological conditions

Cleveland Clinic

Mayo Clinic

Medline Plus Produced by the US National Institutes of Health with information on virtually every health topic and extensive list of links

UrologyHealth.org The patient information site of the American Urological Association.