Prostate UK - Prostate news article

Prostate news article, December 2007

DEVELOPMENTS IN BPH DIAGNOSIS AND MANAGEMENT OVER THE PAST TWO DECADES

Professor Roger S Kirby, Chairman of Prostate UK and visiting Professor to St George's Hospital, London

Much has been learnt over the past 20 years about benign prostatic hyperplasia (BPH) which is the commonest condition to affect men beyond middle age. Almost half of all men older than 65 years have lower urinary tract symptoms (LUTS) consisting of a poor flow and frequency of micturition. When LUTS become severe they may have a severely negative impact on the individual's quality of life. Because BPH is generally a disorder of older men, it is frequently associated with other comorbid conditions such as erectile dysfunction, hypertension and prostate cancer. These need to be identified and taken into account at the time of diagnosis as their presence may impact on treatment strategies for the benign prostatic enlargement itself.

The cause of BPH remains enigmatic in spite of considerable research into the subject. What is certain is that the central portion of the prostate, known as the transition zone (TZ), slowly enlarges over time, resulting in progressive bladder outflow obstruction (Figure 1). The detrusor muscle of the bladder wall responds to this by undergoing hypertrophy and becoming trabeculated. This secondary change results in the symptoms of bladder overactivity including nocturia, urgency and urge incontinence, that are often more bothersome to the patient than the poor flow and incomplete emptying which are due to the prostatic enlargement itself.

Figure 1: Bladder outflow obstruction

Over the past two decades our understanding of the natural history of BPH has come on in leaps and bounds. A great deal of information has stemmed from the well conducted observational Olmstead County study which was initiated in 1990 and has lead to a spate of influential publications(1). The overriding conclusion, backed up by analysis of the placebo arms of medical therapy trials including PLESS and MTOPS, is that untreated BPH is generally a slowly progressive disease. Moreover, a high risk group of patients who are especially at risk of complications, including acute urinary retention (AUR), can be identified (2). These are men with a larger prostate (>40 ccs) higher PSA values and more severe symptoms. These patients should be informed that over time their symptoms are likely to deteriorate and that AUR may occur. An episode of urinary retention which occurs when an individual is travelling can be devastating not only for him but also for his family and has been shown to result in a significant reduction in his quality of life (3).

Guidelines on BPH have been produced which have clarified the way in which men with lower urinary tract symptoms (LUTS) should be investigated and treated (4). The symptom severity and the degree of bother that the symptoms cause should be assessed and enquiries made about co-morbidities. The prostate specific antigen (PSA) should usually be measured, not only to assess the risk of carcinoma of the prostate, but also as the level of this marker is a useful indicator of prostate volume and risk of BPH progression. Ideally, a flow rate and post void residual volume should be documented, however flow meters and ultrasound scanners are not readily available in primary care premises as yet; cystoscopy is no longer a recommended tool for the investigation of uncomplicated BPH. Renal ultrasound or intravenous urography is also regarded as unnecessary as hydronephrosis and renal impairment due to BPH is now rare.

Twenty years ago the gold standard treatment for obstructive BPH was a transurethral resection (TURP) of the transition zone tissue. Nowadays medical treatments have become firmly established as first line therapy for uncomplicated BPH. Alpha blockers are rapidly effective in improving flow and symptoms regardless of prostate size, but have little or no effect on progression of the disorder and there is no firm evidence to suggest that they protect against urinary retention. Patients prescribed alpha blockers should be warned that they may notice tiredness and dizziness as well as nasal stuffiness, but these side-effects tend to diminish over time. Tamsulosin in particular may result in retrograde ejaculation, but this is reversible on cessation of the medication (5). By contrast, 5 alpha-reductase inhibitors (5ARIs) work more effectively in larger prostates (>40 ccs) and in men with higher PSA values (>1.5 ng/ml). Both finasteride and dutasteride may produce erectile dysfunction and loss of libido in 3-5% of patients, while gynaecomastia may result in around 1% of cases. in Both the Medical Treatment of Prostate Symptoms (MTOPS) study and the recently reported CombAT study (Combination of tamsulosin and Avodart) confirmed that a combination of both an alpha blocker and a 5ARI produced the best outcome in terms of symptoms, flow rate and reduction of the risk of disease progression, but at an increased financial cost and an increased risk of side-effects (6). Guidelines to the medical management of BPH are shown in the algorithm in Figure 2. Currently there is some interest in the use of phosphodiesterase type 5 (PDE5 ) inhibitors in treating LUTS due to BPH but no firm evidence yet that they are effective. Trials to evaluate the use of anticholinergic agents to treat the secondary overactive bladder (OAB) component of BPH have generally been disappointing and these agents may provoke AUR as a result of the negative effect on detrusor contractility.

Figure 2: Guidelines to the medical management of BPH
You can view this table more clearly as a .pdf file here

Minimally invasive therapies for obstructive BPH have come and gone over the past two decades. After some initial enthusiasm, balloon dilatation of the prostate has fallen into complete abeyance. Its decline was the result in no small measure to the demonstration that it was no more effective than a simple cystoscopy alone. Microwave therapies probably have some therapeutic benefit, but have never become widely popular. More recently laser ablation of the prostate, initially by side firing laser (which did not stand the test of time) and now by GreenLight (7) or Holmium laser technologies have been advocated by some and are gaining in popularity, although the jury remains out as to whether they will eventually replace transurethral resection of the prostate (TURP). Some researchers have even injected Botulinum toxin (Botox) into the prostate with reportedly good effect, but randomised clinical trials are required to corroborate their findings.

When complications of BPH occur such as AUR, bladder stone formation, recurrent urinary tract infections (UTIs) or haematuria then a urological opinion should be sought. Other important diagnoses such as carcinoma-in-situ of the bladder may masquerade as BPH and require urine cytology, cystoscopy and bladder biopsy to confirm. Carcinoma-in-situ is usually associated with more dysuria than BPH and microscopic or macroscopic haematuria is also often present. Treatment of this condition with intravesical BCG immunotherapy is often very effective, but sometimes cystectomy may be required if invasive bladder cancer has developed.

The thought of undergoing a transurethral resection of the prostate (TURP) is often is often a source of trepidation to patients, but with modern refinements, including state-of-the-art digital camera systems that allow significant magnification and better haemostasis, uniformly good outcomes can be achieved with only a very few days in hospital. The physical removal of the enlarged transition zone results in a much improved flow and more effective bladder emptying. Secondary symptoms of urgency, frequency and nocturia take longer to settle but disappear within a few months. Side-effects include retrograde ejaculation, which is permanent but not too troublesome provided the patient has been counselled about this preoperatively.

No one knows what the future holds, but it seems unlikely that the next twenty years will see as many sea changes in the diagnosis and management of BPH as have the last two decades. During this time span the natural history of the disorder have been clarified, the way in which it is investigated formalised, and its manner of first line treatment changed from surgery to pharmacotherapy. Now the race is on to develop a technology that will genuinely replace TURP; only time itself will tell whether or not that “Holy Grail” will ever be reached.

Roger S Kirby, 14th December 2007

References

1. Jacobsen SJ, Jacobson DJ, Girman CJ, et al: Treatment for benign prostatic hyperplasia among community dwelling men: The Olmsted County study of urinary symptoms and health status. J Urol 1999;162:1301--1306.
2. Jacobsen SJ, Jacobson DJ, Girman CJ, et al: Natural history of prostatism: Risk factors for acute urinary retention. J Urol 1997;158:481--487.
3. Thomas K, Oades G, Taylor-Hay C, Kirby RS. Acute urinary retention: what is the impact on patients’ quality of life? BJU Int 2005, 95, 72-76.
4. Speakman MJ, Kirby RS, Joyce A, Abrams P, Pocock R. Guideline for the primary care management of lower urinary tract symptoms. BJU Int 2004 ;93: 985-90.
5. Lepor H for the Tamsulosin Investigator Group: Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Urology 1998;51:892--900.
6. McConnell JD, Roehrborn CG, Bautista OM et al: The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N. Engl. J. Med. (2003) 349:2387-2398.
7. Gomez Sancha F, Bachmann A, Choi BB, Tabatabei S, Muir GH, Photoselective vaporization of the prostate (GreenLight PV): lessons learnt after 3500 procedures. Prostate Cancer and Prost Dis. 2007; 10 316-322.