Benign Prostatic Disease
Gordon Muir
Consultant Urologist
King's College Hospital London SE5 9RS
Benign prostatic disease is an ubiquitous problem in Western society: an average GP with 2000 patients can expect to have around 150 men registered who have lower urinary tract symptoms severe enough to consider seeking treatment at some time. Benign disease of the prostate can be divided into two broad groups: obstructive and inflammatory; over recent years urologists have tended to move away from the rather nebulous term “prostatism” towards a more descriptive symptom terminology. Thus the terms used in this review will include “benign prostatic enlargement,” “bladder outflow obstruction” (usually but not always secondary to an enlarged prostate), “storage symptoms” and “voiding symptoms.” These last two terms try to divide symptoms into those which arise as a result of difficulty in passing urine where obstruction exists and those where problems arise as a result of overactive or underactive bladder muscle contraction.
Storage Symptoms
Frequency
Urgency
Nocturia
Dysuria
Incontinence
Incomplete emptying
Voiding Symptoms
Hesitancy
Poor Stream
Double voiding
Retention of Urine
Table 1
Lower Urinary Tract Symptoms
As will be seen, patients will be more concerned by the majority of Storage symptoms than Voiding symptoms. It is thought that the majority of these come about as a result of bladder muscle hypertrophy and overactivity secondary to obstruction
The vast majority of middle aged and elderly men presenting to general practitioners with complaints related to their prostate will have bladder outflow obstruction in association with benign prostatic enlargement.
Obstructive Prostatic Disease
Benign Prostatic Enlargement (BPE or BPH):
Histological evidence of stromal and epithelial hyperplasia in an enlarged gland
Bladder Outflow Obstruction (BPO):
Subvesical obstruction however caused
Benign Prostatic Obstruction (BPO):
Obstruction in the presence of BPE
Bladder Neck Obstruction
Obstruction without enlargement of the prostate
Inflammatory Prostatic Disease
Acute Bacterial Prostatitis
Chronic Bacterial Prostatitis
Prostatic pain (aka “Prostatodynia”)
Table 2
Benign Prostatic Disease
Epidemiology of Prostatic Disease
All intact men will have some prostatic enlargement as they grow older. 30% of men in their seventies may have objective symptoms severe enough to warrant investigation and treatment. It is almost impossible to obtain cadaveric tissue from elderly men in the UK without histological evidence of benign prostatic hyperplasia. While a large prostate does not always cause symptoms there is a strong link between prostate size and bladder outflow obstruction.
There are enormous differences world-wide in the incidence of benign prostatic enlargement; in general developed countries with a diet rich in animal fats have the highest incidence. Racial differences are striking, with black men having a higher incidence than whites who in turn have a higher incidence than Asians. This relationship is paralleled in prostatic cancer as well as in the normal serum testosterone levels in the three groups, and in prostate cancer we now have clear evidence that some foodstuffs such as soya and lycopene (tomato pigment) are protective: this may prove to be the case for benign disease also.
In underdeveloped countries shorter male life expectancy and under-reporting may bias the figures, but migrant studies do tend to confirm the epidemiological suggestions that this is a disease of western lifestyles. Possibly the most attractive hypothesis is that the pathogenesis is mediated by metabolism of ingested fats to produce excess amounts of circulating sex hormone homologues which may derange the normal interaction between the prostate stromal cells and their epithelial neighbours. Prostatic enlargement does not seem to have occurred in eunuchs who were castrated before puberty.
While the British man with symptoms of benign prostatic disease appears rather more stoical than his North American or Western European cousins, it is obvious that with only one consultant urologist for every 120,000 people in the UK, there is no way that every elderly man with symptoms of bladder outflow obstruction can be managed exclusively in a hospital based system. Thus with the combination of an increasingly aged population and heightened awareness of men's' health issues it is vital that the majority of these patients should be looked after in a primary care
Should benign prostatic disease be screened for and who should be referred?
Bladder outflow obstruction (BOO) is a term covering a constellation of symptoms which range from a slightly slow urinary stream, through urgency and incontinence, to end stage obstructive renal failure. There is as yet no proof that screening for benign prostatic disease is of value. A rational approach seems to be to try to identify those men who are at risk of developing serious complications from their prostatic disease.
Table 3: Groups of men with urinary symptoms
Most men with urinary symptoms will fall into one of these groups
For the vast majority of men with bothersome symptoms, a number of simple screening tests will make sure there is no serious problem. In our practice we recommend a clinical examination, urinalysis with culture if any abnormality is found, and a serum creatinine estimation, with a check on the serum PSA. In the case of elevated creatinine we would recommend a renal and bladder ultrasound. If haematuria is present, urgent urological referral is of course necessary. A urinary flow rate ( most men with peak flow of less than 10ml/s will be obstructed) and bladder ultrasound will complete the baseline investigations. Many general practitioners will now have access to these last two tests, and whereas they are not mandatory they do give some objective measure of any likely obstruction present. The international prostate symptoms score (IPSS) will also give a good baseline of the patient's perceived symptoms, and can be filled in by most patients without assistance.
Assuming however there is no abnormality in the tests mentioned, the patient can be treated symptomatically. In many cases reassurance will be sufficient, since most men remain somewhat reticent about discussing their problems with their peers and may be unaware that they are not the only sixty five year old getting up once a night to pass urine. Similarly, simple advice such as avoiding large amounts of diuretic drinks (tea, coffee, alcohol), particularly in the evenings, may make life tolerable without more complex treatment.
Baseline Tests to Assess Bladder Outflow Obstruction
Medical therapy proposed
DRE suspicious
Symptoms suggestive of prostate cancer
Elevated creatinine
Eligible for radical treatment if early prostate cancer present
Who should be referred?
With regard to dangerous signs or symptoms, the urologist's prime concern is to try to avoid men developing urinary retention or obstructive renal failure, thus the concern with creatinine and renal ultrasound.
Other worrying symptoms include the presence of proven urinary tract infections, which might indicate either poor bladder emptying or a bladder stone. Bladder pain is an unusual feature of benign prostatic disease, and can indicate either infection, stone or possible cancer of the bladder. Visible haematuria is never normal.
Patients whose main complaint is of incomplete emptying are usually right about their bladder function and if bladder ultrasound shows a residual volume of greater than 150ml referral is appropriate due to the possible risk of acute or chronic retention developing.
IN many cases it will be the case that a general urological opinion can be given based on a GP's findings and the results of tests: cultivating an informal link with your local urologist will be very helpful in keeping referral rates down for such patients and in our practice at King's College Hospital we are always happy to give advice (by letter, telephone or now by secure email) in respect of patients who do not fall neatly into one of the above groups.
The place of PSA testing and detection of prostate cancer will be dealt with in the second of these articles.
Refer to Urologist
Urgent
Elevated Creatinine or hydronephrosis
Haematuria
Suspicion of significant prostate cancer
Bladder or prostate pain
Urinary tract infection
Suspected retention (residual urine volume >300ml)
Non-Urgent
Failure to respond to medical therapy
Residual urine volume >150ml
Severe symptoms
Table 4:
Patients who should be referred to a urologist
Medical Treatment For Bladder Outflow Obstruction due To Benign Disease
TURP remains the benchmark therapy for benign prostatic obstruction, but most men do not require surgery in the first instance. Many men will be happy with the reassurance that their symptoms are not significantly different from the average for their age. If their symptoms are bothersome however, medical treatment is indicated.
There are currently two groups of drugs which have been shown to improve symptoms and flow rates in men with BOO.
Alpha blockers act by relaxing the smooth muscle of the prostate and have varying degrees of selectivity. The major problem with these drugs has historically been of hypotension, but the most recently developed are more selective and have a lower risk of this. My own practice is to recommend these drugs in all men with small prostates (the serum PSA is a good guide to this): normally a selective alpha blocker such as Tamsulosin (Flomax) or Alfuzosin (Xatral-XL) is used. In men who have hypertension, the use of a less selective alpha blocker such as Doxazosin (Cardura-XL) may help treat both the prostate and the hypertension: this is usually more of a decision for the primary care physician than the urologist. Most patients who respond to alpha blockers will have a noticeable improvement in their urinary flow within a few weeks. It may however take some months for any of the storage symptoms shown in table 2 to improve.
For men with larger prostates (PSA greater than 2.5 ug/l with no concern about malignancy) there is now evidence that treatment with the 5α-reductase inhibitor Finasteride (Proscar) can produce a durable reduction in prostate size and symptoms over a long time period by local inhibition of hormonal activity in the prostate. Long term Proscar therapy reduces the risk of either developing retention of needing surgery by around 50%. Patients should however be warned that, unlike alpha blockers, it may take some time before a symptomatic benefit is seen. Although not licensed for this indication, Proscar appears particularly effective for men with haematuria of prostatic origin.
Numerous herbal therapies exists and some have been shown to have significant effects in clinical trials. The best characterised is Saw Palmetto, derived from the berries of a cactus like plant, which has a weak effect on 5-alpha reductase. It has not achieved the same results as finasteride or alpha blockers in direct comparative tests.
Not all men will benefit from drug therapy and of course if symptoms remain bothersome despite treatment, urological referral is appropriate.
Surgical Treatment of Bladder Outflow Obstruction
transurethral Resection of the Prostate (TURP) is one of the best characterised minimally invasive procedures. More than 95% of prostate surgery for benign disease can now be done endoscopically and if patients are well selected as outlined above, satisfaction rates of over 90% can be obtained. The procedure involves passing a telescope through the urethra and using an electrosurgical loop to remove prostate tissue, forming a cavity where there had been obstruction. In smaller prostates the simpler technique of Bladder Neck Incision (BNI) involves cutting through the bladder neck muscle and prostate tissue around the bladder neck to open the bladder outlet without removal of prostate tissue. Both these operations are usually done under either general or spinal anaesthesia and can be carried out in most cases with between one and four nights in hospital. A catheter is left in the bladder for one to three days. In patients who have presented with chronic retention of urine (residual volume > 1000ml) it is often the case that voiding will not be established immediately post operatively and these patients may need to be counselled about the post operative need for an indwelling catheter or intermittent self catheterisation for several months until bladder muscle function recovers.
Done well in selected patients, incontinence should not be a problem after prostate surgery although patients with severe storage symptoms may require several months before the bladder settles down (most urologists would perform formal pressure flow urodynamic studies on these patients pre operatively to confirm the presence of obstruction).
Sexual side effects are common after prostate surgery, with retrograde ejaculation occurring in more than 70 % of TURP patients and around 30% of BNI patients. This phenomenon occurs due to the destruction of the internal sphincter which usually closes during ejaculation. Some men will complain of a feeling of less pleasurable ejaculation, especially if they have not been fully counselled. Impotence is fairly rare as a direct result of transurethral surgery; it is thought that the mechanism of any impotence following TURP is due to conduction of the diathermy current into the penile nerves lying just behind the prostate gland. From a counselling point of view, it is unlikely that the risk of impotence in a normally potent man is greater than 5%.
Open surgery for benign disease is now limited almost exclusively to those patients with very large prostates (more than 100cc). It has similar results and complications to TURP but does require around a week in hospital due to the incision which is made in the front of the prostate; there is also a risk of severe bleeding as a result of the open operation.
New treatments are being trialled all the time in prostatic disease and indeed the development of the drugs mentioned earlier has changed our practice enormously. In terms of new, less invasive surgical techniques the results have sadly been less impressive and a number of new energy delivery systems (LASER, ultrasound, hyperthermia) have fallen by the wayside in the last few years due to their inability to stand comparison to the results of TURP. The use of high electric energy probes (Vaportrode™) to vaporise the prostate was easy to learn but much slower than TURP and had higher incontinence and impotence rates.
The two most promising new therapies appear to be methods of removing prostate tissue by laser. One of these, Holmium laser enucleation of the prostate, cuts out the prostate tranurethrally in large pieces which are then removed from the bladder using a morcellating tool. While very effective, this technique is very hard to learn and has been associated with some major complications, so has not been widely adopted. A more promising recent addition to our armamentarium is a very powerful modulated KTP-YAG laser beam (Niagara™ prostate vaporisation)which is absorbed by the haemoglobin pigment in tissue, resulting in instantaneous vaporisation; bleeding is close to zero despite a generous TURP like cavity being created instantly.
Initial results using this technique in a number of different centres in the USA have consistently shown a fast operating time and little or no bleeding, with most patients now being able to go home on the day of the procedure with no catheter. While results beyond one year are awaited, after six or more months improvements in symptoms and urine flow are at least as good as TURP. Strikingly, very few patients report pain after the procedure: pain and burning on urinating have limited both laser techniques and TURP in the past. Also, the initial impression is that sexual side effects are reduced compared to the standard technique.
We have now treated a number of men with proven outflow obstruction listed for prostatectomy (including some with very large prostates who in most hospitals would have been subjected to open surgery). Initial results are excellent and this may indeed offer a real, ambulatory, alternative to TURP.
Bladder Neck Incision
Suitable for smaller prostates
Low incidence of sexual side effects
No removal of tissue
TURP
Suitable for most prostates
Very high disobstruction rate
Orgasmic dysfunction common
Open Prostatectomy
Reserved for very large prostates
Excellent results
Similar sexual side effects to TURP
Major operation for large glands
Microwave and Thermotherapy Systems
Outpatient Treatment with low morbidity
Initial Results very disappointing compared to sham treatment or TURP
Newer systems (T3, TUNA) show considerable promise for selected patients
LASER prostatectomy
New methods of LASER prostatectomy (Niagara, Holmium VLAP) may well be poised to replace TURP and open prostatectomy
Table 5: Physical treatments for Benign Prostatic Disease
Take Home Points
Most men with BOO can be happily managed in primary care
Primary and elderly care physicians should identify the at risk patients above for referral to urologists
PSA testing is a complex issue: a good informal relationship with a local urologist will be invaluable in testing and interpretation.
Medical therapy is effective in many with a low side effect profile:
selective alpha blockers are rapidly effective
Finasteride may be effective long term in larger prostates (PSA greater than 2.0 ug/l)
TURP remains an excellent surgical option for patients refractory to drug therapy, but may be replaced in the next few years by laser vapourisation or enucleation of the prostate
Figures:
Incidence of BPH: In text
Cystoscopic view of an obstructing prostate
The Niagara laser creating a clear channel to the bladder
Urinary flow rates: normal and obstructed