Prostate news article, June 2009

FACILITATING THE MEDICAL MANAGEMENT OF BPH IN PRIMARY CARE   Article by:   Professor Roger Kirby, Chairman, Prostate UK

In spite of the creation of several guidelines specifically dealing with the problems resulting from benign prostatic hyperplasia (BPH)1,2, general practitioners (GPs) still seem reluctant to embrace the diagnosis and management of this highly prevalent disorder. There are a number of reasons for this: firstly, in the UK, BPH is not included in the so-called Quality and Outcomes Framework (QOF) and therefore there is little incentive for GPs to get involved. Secondly, there is still considerable uncertainty about the role and value of digital rectal examination (DRE) and prostate specific antigen (PSA) testing as a means of identifying BPH and excluding prostate cancer. Thirdly, many GPs are unfamiliar with the medications used for the management of BPH and how they should be best deployed. Finally, there is still confusion about the target values for symptom score and reduction of acute urinary retention (AUR) rates that ideally should be achieved in response to medical therapy and if and when the patient should be referred for specialist evaluation.

Taking these points in turn: the QOF system in England was designed to improve quality of care and clinical outcomes in family practice and most agree that its implementation has been beneficial in terms of the reduction of cardiovascular risk and diabetes management. Many conditions however, not least BPH, remain outside its remit and, partly as a result, under-diagnosed as well as under-treated. There are certainly several arguments to be made for bringing BPH, the most common and bothersome condition to afflict men beyond middle age, under the QOF umbrella. The disease undoubtedly has a significant public health impact, since it is both prevalent and extremely bothersome, with important sequelae including AUR and the need for surgery. Diagnosis and treatment are well within the capabilities of primary care and specialist diagnostic tests are not routinely required. Evidence based treatment guidelines exist1,2 and the results of treatment are easily measured including improvement in IPSS and reduction in AUR rate.

DRE is a straightforward way of assessing prostate size and excluding palpable cancer. PSA testing, however, has been subjected to criticism because of the lack of sensitivity and specificity of the assay for prostate cancer. In fact, in the absence of cancer, serum PSA values provide a useful surrogate for prostate volume and also helps to inform the clinician which medical therapy for BPH is likely to be most effective3. In the recently reported European Randomised Study of Prostate Cancer Screening (ERSPCS)4 prostate cancer mortality was reduced in the arm screened by PSA testing by as much as 20%, but at the cost of considerable over-diagnosis of what may have been clinically insignificant cancers. Recently, however, evidence has emerged that a rise in PSA value in an individual patient over time – so called PSA doubling time – may provide a means of differentiating clinically aggressive cancers from the more indolent tumours that may never require treatment or cause harm5. Furthermore, there are new molecular markers, including the urine based PCA3 test, which may help to make this important distinction6.

Evidenced based medical therapy for BPH involves the use of either an alpha blocker, a 5-alphareductase inhibitor (5-ARI) or a combination of the two classes of medication. Several guidelines have been devised to help clinicians use these classes of drugs effectively. Both the IUCD guidelines1 and the British Association of Urological Surgeons (BAUS) guidelines2 (Fig 1) emphasize that men who are symptomatic and have a small prostate and a PSA value below 1.4 ng/ml are usually best treated with an alpha blocker. Those who are not troubled unduly by symptoms, but have an enlarged prostate and a PSA > 1.4 ng/ml and are consequently at risk of BPH progression, should be considered for treatment with a 5–ARI. Men with a larger prostate, a PSA greater than 1.4 ng/ml and who have troublesome symptoms are best managed with a combination of both therapies. Whichever type of medical therapy is decided upon, the patient should be informed about the possible side-effects of alpha blockers, which include tiredness, dizziness, nasal stuffiness, and, with tamsulosin and silodosin especially, anejaculation7. They should also be informed that 5-ARIs may cause sexual dysfunction in around 3-5% of those receiving medication8. Those taking combination therapy are of course exposed to both sets of side-effects, but all of them are reversible on cessation of medication. The recently updated CombAT study confirms that combination therapy achieves better outcomes than either form of monotherapy after 4 years9. The SMART study suggests that in some patients after a period of time the alpha blocker therapy could be stopped in some individuals once 5-ARI treatment as had time to induce sufficient shrinkage of the prostate and improve the symptoms10.

In many other disease areas where medical therapy is deployed, including hypertension and hyperlipidaemia, "goals of therapy" have been clearly defined. A diastolic blood pressure consistently below 90 mm/Hg or an LDL cholesterol below 3.0 microgm/L are targeted, as both these have been demonstrated to reduce the risks of cardiovascular events. In BPH one could argue that a symptom score reduction of at least three points and a significant reduction in the rate of AUR might represent realistically achievable targets. In men with prostatic enlargement a longer term treatment goal might be a reduction of progression events such as AUR or the need for surgery of around 50%, since that was the outcome achieved in the Medical Treatment of Prostate Symptoms (MTOPS) study11. Patients failing to achieve these treatment goals should usually be considered for referral to a urologist.

In conclusion, a move by family practitioners to become more involved in the management of the very men with bothersome lower urinary tract symptoms (LUTS) resulting from BPH seems both appropriate and logical. There will, of course, still be a need to refer men with complicated BPH to specialist urologists, including those individuals with AUR, recurrent urinary tract infections (UTIs) and haematuria, as well as those suspected of harbouring clinically significant prostate cancer. Surgery, usually by transurethral resection of the prostate (TURP), or by newer modalities such as Holmium Enucleation of the Prostate (HoLEP)12 will still be required in a substantial minority of cases, and biopsy of the prostate will very often be required to diagnose or rule out cancer. A "shared care" approach of GPs working in tandem with specialists, informed and driven by the evidenced-based IUCD and BAUS guidelines seems likely to best way to provide the highest standard of care to the very many sufferers of this increasingly prevalent and highly bothersome disorder, and has the potential to provide a better, more efficient way for all of us to work 13,14.

References:
1. Speakman MJ, Kirby RS, Joyce A et al. Guideline for the primary care management of male lower urinary tract symptoms. BJU Int 2004;93: 985–90.

2. Abrams P et al. IUCD guidelines J Urol 2009.

3. Roehrborn CG, Boyle P, Bergner D, Gray T, Gittelman M, Shown T, et al.: Serum prostate–specific antigen and prostate volume predict long–term changes in symptoms and flow rate: results of a four–year, randomized trial comparing finasteride versus placebo. PLESS Study Group. Urology 1999 Oct;54(4):662–669.

4. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate–cancer mortality in a randomized European study. N Engl J Med. 2009 Mar 26;360(13):1320.

5. Philip M. Arlen, Fernando Bianco, William L. Dahut, Anthony D'Amico et al Prostate–Specific Antigen Working Group's Guidelines on PSA Doubling Time. J Urol. 2008 June; 179(6): 2181–2186.

6. Kirby RS, Fitzpatrick JM, Irani J. Prostate cancer diagnosis in the new millennium: strengths and weaknesses of prostate-specific antigen and the discovery and clinical evaluation of prostate cancer gene 3 (PCA3). BJU Int. 2009 Feb;103(4):441–5.

7. Kaplan S: Current role of alpha–blockers in the treatment of benign prostatic hyperplasia. BJU Int 2008 Nov;102 Suppl 2:3–7.

8. Roehrborn CG, Marks LS, Fenter T, Freedman S, Tuttle J, Gittleman M, et al.: Efficacy and safety of dutasteride in the four–year treatment of men with benign prostatic hyperplasia. Urology 2004 Apr;63(4):709–715.

9. Barkin, M. Guimara, G. Jacobi et al Alpha–Blocker Therapy Can Be Withdrawn in the Majority of Men Following Initial Combination Therapy with the Dual 5a–Reductase Inhibitor Dutasteride. European Urology 44 (2003) 461–466.

10. Roehrborn C, Siami P, Barkin J, Damiao R, Major–Walker K, Morrill B, et al.: The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2–year results from the CombAT study. J Urol 2008 Feb;179(2):616–621.

11. 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; 349:2387–98.

12. Gilling P. Holmium laser enucleation of the prostate (HoLEP). BJU Int 2008, 101:131–42.

13. Kirby RS, Fitzpatrick JM, Kirby MG, Fitzpatrick A Shared Care for Prostatic Diseases. Isis Medical Media, Oxford, 1995.

14. Tanguay S, Awde M, Brock G, Casey R, Kozak J, Lee J, Nickel JC, Saad F. Diagnosis and management of benign prostatic hyperplasia in primary care.Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S92–S100.