Portal de Periódicos da CAPES

STEP: Simplified Treatment of the Enlarged Prostate

2009; Wiley; Volume: 64; Issue: 4 Linguagem: Inglês

10.1111/j.1742-1241.2009.02304.x

1742-1241

Matt T. Rosenberg, Martin Miner, Peter Riley, David R. Staskin,

Genital Health and Disease

International Journal of Clinical PracticeVolume 64, Issue 4 p. 488-496 REVIEW ARTICLEFree Access STEP: Simplified Treatment of the Enlarged Prostate M. T. Rosenberg, M. T. Rosenberg Department of Family Medicine, Mid-Michigan Health Centers, Allegiance Health System, Jackson, MI, USASearch for more papers by this authorM. M. Miner, M. M. Miner Men's Health Center, Miriam Hospital, Warren Alpert Medical School, Brown UniversitySearch for more papers by this authorP. A. Riley, P. A. Riley Department of Family Medicine, Mid-Michigan Health Centers, Allegiance Health System, Jackson, MI, USASearch for more papers by this authorD. R. Staskin, D. R. Staskin Tufts University School of Medicine, Caritas-St. Elizabeth's Medical CenterSearch for more papers by this author M. T. Rosenberg, M. T. Rosenberg Department of Family Medicine, Mid-Michigan Health Centers, Allegiance Health System, Jackson, MI, USASearch for more papers by this authorM. M. Miner, M. M. Miner Men's Health Center, Miriam Hospital, Warren Alpert Medical School, Brown UniversitySearch for more papers by this authorP. A. Riley, P. A. Riley Department of Family Medicine, Mid-Michigan Health Centers, Allegiance Health System, Jackson, MI, USASearch for more papers by this authorD. R. Staskin, D. R. Staskin Tufts University School of Medicine, Caritas-St. Elizabeth's Medical CenterSearch for more papers by this author First published: 05 February 2010 https://doi.org/10.1111/j.1742-1241.2009.02304.xCitations: 6 Matt T. Rosenberg, MD,Mid-Michigan Health Centers, 214 N. West Ave, Jackson, MI 49201, USATel.: + 1 517 784 9189Fax: + 1 517 784 9657Email: matttoren@yahoo.com Disclosures Matt T. Rosenberg, MDConsultant: Abbott, Allergan, Astellas, GlaxoSmithKline, Ortho-McNeil, Sanofi-Synthelabo, Schering-Plough, Roche, and Watson.Speaker's Bureau: Abbott, Allergan, Astellas, Forest, GlaxoSmithKline, Novartis, Ortho-McNeil, Pfizer, Sanofi-Synthelabo, Schering-Plough, and Watson.Martin M. Miner, MDConsultant: Auxillam, Bayer, GlaxoSmithKline, Sanofi-Aventis, and Solvay.Philip A. Riley IV, BANo disclosures to report.David R. Staskin, MDAdvisory Boards: GlaxoSmithKline, Astellas, Allergan, Pfizer, Watson.Speaker's Bureau: Astellas, Allergan, Pfizer, Watson.Research: Allergan, Astellas, Pfizer. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Summary We propose a simple and practical approach to the identification, evaluation and treatment of lower urinary tract symptoms (LUTS) resulting from an enlarging and obstructive prostate. The proposed Simplified Treatment for Enlarged Prostate (STEP) plan is a logical guide to patient management by the primary care provider (PCP). Symptoms of enlarged prostate (EP) are common and may frequently progress into a condition with profound adverse effects on quality of life. Despite the high prevalence, EP is underdiagnosed and undertreated. This situation may result from patient- and provider-related issues. Assessment of symptoms of EP should be initiated with a discussion of LUTS. Evaluation includes a focused history, physical examination and selected laboratory tests. Certain factors put the symptomatic patient at risk for disease progression; however, not all factors can be readily evaluated in the PCP setting. The serum prostate-specific antigen (PSA) level acts both as an indicator of prostatic size and a screening tool for prostatic cancer, and thereby provides an important tool for PCPs. The STEP plan is a logical guide to patient management. Step 1, watchful waiting, is appropriate in patients with symptoms that are not bothersome. If symptoms cause bother, the initiation of an alpha-blocker (AB) in step 2, provides relatively rapid symptom improvement. Patients with bothersome symptoms and a PSA ≥ 1.5 ng/ml are at risk for progression and consideration should be given to combination treatment with an AB and a 5α-reductase inhibitor (step 3). Patients with refractory symptoms should be referred to a urologist (step 4). Identification, evaluation and management of EP are within the domain of the primary care setting. The STEP approach provides a simple and practical framework for PCPs to manage most men with symptoms of EP. Review Criteria We identified recommendations and guidelines for the identification and management of patients with EP from various societies, including the American Urological Association and European Association of Urology. Through PubMed searches, we identified screening methods, diagnostic algorithms and randomised clinical trials related to the management of EP. This review represents an interpretation and adaptation of this information into a practical approach that can be applied to the primary care setting. Message for the Clinic Symptoms of EP are common and may frequently progress into a condition with profound adverse effects on quality of life; however, this condition is often left undiagnosed and untreated. Primary care is an optimal setting for the identification, evaluation and management of EP. The proposed Simplified Treatment for Enlarged Prostate (STEP) plan is a practical and logical guide to patient management by the primary care provider. Introduction There are several undeniable facts about the prostate. First and foremost, as far as prevalence and impact is concerned, it can affect half of the population. It has a function in that it contributes volume to seminal fluid which is of obvious importance during years of fertility. It gets larger as the male ages and is located in an anatomical location that may not be completely desirable as its growth commonly obstructs emptying of the urinary bladder (1). Many men will have an enlarged prostate (EP) and a percentage of these men will develop bothersome symptoms as a result of obstruction. Even without significant growth, a patient can experience obstructive symptoms. Either situation can cause quality of life concerns for the patient, and may even evolve into life-threatening situations when ignored. For years the prostate has been in the domain of the urologist and the most common therapeutic intervention was surgical reduction of the gland. Beginning in the late 1980s, medications became available that provided symptomatic relief for the affected patient, which markedly reduced the rate of surgical intervention. However, symptomatic relief does not change the progression of the enlarging prostate and this growth can result in worsening symptoms in some patients. Therefore, for some patients, this treatment relieved symptoms for a short period of time and surgery was only temporarily delayed, rather than avoided. The idea of disease progression and prevention of long-term negative outcomes is familiar to the primary care provider (PCP). Hypertension, diabetes and hyperlipidaemia are all diseases that should be treated aggressively early to prevent progression and ultimately result in better outcomes. Early identification, before symptoms have progressed, might best be accomplished in the office of the PCP. Thus, a logical follow-up question becomes, is early identification and management of the patients at risk for EP feasible in the office of the PCP? The urological community has performed an extraordinary job in developing our understanding of the prostate, the associated symptoms, and progression potential, which in turn, makes it more practical for the PCP to be a first-line of defence, or even offence, against EP. To be adequately prepared to provide this care, the needs of the PCP can be summed up in three words, 'simple', 'effective' and 'safe': a 'simple' and efficient approach to evaluate a symptomatic patient; 'effective' treatment options that can be prescribed or performed within the primary care setting; and finally, a 'safe' approach to patient management, with minimal chance of initiating therapy that can result in a poor outcome for the patient. In this article, we collate the recommendations of various societies for the identification, evaluation and treatment of the patient with symptomatic EP and discuss how the PCP can implement these approaches in his or her office. We understand the time constraints of the PCP in the current healthcare environment and, subsequently, offer a stepwise approach to the treatment of EP that we hope will make the process more straightforward. Definitions The term lower urinary tract symptoms (LUTS) describe symptoms typically arising from the prostate or bladder. There are many terms used to describe the EP and related consequences: benign prostatic hyperplasia (BPH), benign prostatic enlargement (BPE), bladder outlet obstruction (BOO), benign prostatic obstruction (BPO) and EP, to name a few. It is understood that prostatic enlargement need not be present for prostatic obstruction to occur; however, enlargement is the most common cause. In this article, we describe the patient with symptoms of obstruction as having EP, which will include obstructive symptoms of poor flow, hesitancy and intermittency. Frequency, urgency and nocturia are described as irritative symptoms and are proposed to be a result of obstruction (they improve with relief of obstruction). These symptoms are also extremely bothersome and are included in all outcome measurements. Epidemiology and prevalence There is no doubt about the prevalence of BPH in men. In the U.S., BPH has a prevalence of 40% amongst men 60 years or older and 90% for men 80 years or older (2). Because of the ageing population, the absolute number of patients affected will subsequently increase. Left untreated, men with symptomatic BPH/BPE have a 23% lifetime risk of developing acute urinary retention (AUR) (3). If a man has obstructive symptoms and is over the age of 60 years, he has a 39% probability of undergoing surgery related to the prostate within 20 years (4). Despite the large number of men affected by LUTS, the number of men who seek medical attention is extremely low. While 90% of men reported LUTS in the Multinational Survey of the Ageing Male (MSAM-7), only 19% sought medical care and only 11% actually received treatment (5). This condition also generates significant cost. In 2000, BPH generated $1.1 billion in healthcare costs and accounted for over 4.4 million office visits, 117,000 emergency department visits and 105,000 hospitalisations in the U.S. (6). Clearly there is opportunity for an efficacious and cost-effective approach to treatment. EP as a progressive disease The natural history of EP is that of a progressive disease. Emberton et al. noted several indicators of disease progression which include worsening of symptoms, urinary tract infections (UTIs), bladder stones, decrease in urinary flow and increase in prostate size, as well as emergent outcomes such as AUR and the need for surgery as a result of retention or symptom deterioration (7). The Olmsted County study followed a randomly selected cohort of men aged 40–79 for up to 12 years to study symptoms of EP. The data revealed a decrease in flow rate of 2% per year and prostate growth of 1.9% per year (3). This study also found an average increase of 0.18 points per year in the International Prostate Symptom Score (IPSS), a validated survey used to assess the severity of prostate-related symptoms (8, 9). Overall, this study noted that close to one-third of participants had a significant worsening of symptoms after 92 months (10). In the Medical Therapy of Prostatic Symptoms (MTOPS) study, clinical progression over 4 years in the placebo arm was 17.4%, with the majority of cases (78%) defined by symptom worsening (11). Quality of life impact In a study designed as a longitudinal cohort, men with LUTS showed a greater impairment of general health status than those with chronic illnesses such as gout, hypertension, angina or diabetes, as assessed by the generic scale Short-Form 36 (12). Some patients with symptomatic BPH are driven to seek health care because their quality of life is decreased. These men are bothered by their symptoms, they have interference in their daily activities, their quality of sleep is reduced, they are increasingly worried about their health, and their sexual relationships are affected detrimentally (13-15). Behavioural adaptations are common in this group, and many men with EP avoid fluid intake before bed, travel or when access to bathroom facilities are limited (16). Information is known about patients identified with the symptoms; however, one must also consider how many suffer in silence. Many men believe their symptoms are a normal part of ageing and do not seek help. Furthermore, frequently the provider does not routinely enquire about these symptoms, or do they believe any symptoms would warrant therapy (5). Miner found discrepancies between the treatment practices of these conditions by urologists and PCPs. He speculated that the differences could possibly exist because PCPs view LUTS predominantly as a quality of life issue, but do not consider the issue of progression (17). By providing their patients with education regarding normal and abnormal function of the urinary tract, the PCP can open the door to discussion regarding EP and its impact on quality of life. The magnitude of bother associated with this impact; however, can only be adequately assessed by the patient. While treatment of EP in the symptomatic patient is an option, lack of awareness of the disease is not. A brief review of the pathophysiology of EP As the male ages, the prostate grows through cellular proliferation and expansion. As a result, BPH is the most common benign neoplasm amongst American men (6). This size increase mechanically constricts the urethra and subsequently impairs flow. This is the static or mechanical component of EP and why therapy aimed at reducing the prostate volume (medical or surgical) is thought to improve symptoms. The dynamic component of EP involves the inadequate relaxation of smooth muscle in the area of the prostate and bladder neck during micturition (16). The contraction of this smooth muscle is mediated by α-adrenergic receptors and therapy is aimed at facilitating relaxation by inhibiting this action. 5α-Reductase inhibitors (5ARIs) work on size reduction whereas α-adrenergic blockers (AB) allow bladder neck relaxation. Identification It is clear that EP is a disease identified by its symptoms. A patient could have a large prostate and no symptoms, or a small gland and have severe symptoms and bother. Nevertheless, it is the symptoms that bring the problem to the attention of the provider, and bother drives the informed patient to treatment. All of the guidelines suggest the use of validated questionnaires to assess the degree of symptoms. Although recommended and acknowledged by many providers, the reality is that time in a busy practice does not necessarily allow for the implementation of these tools (18). Patients seem most concerned by symptoms centred on nocturia and flow, and a logical approach may be to address these two points (16). Nocturia questions are fairly obvious: 'do you get up at night to urinate and does this bother you?' Flow is fairly easy to assess as well. In his text on urodynamics, Abrams does not note a numerical rate of flow that designates obstruction; however, he does define good flow as a 'smooth arc-shaped curve with high amplitude' and without interruption. By contrast, weak flow is likely to be interrupted (19). Most men will have a good perception of their flow and can answer the question: 'is it a comfortable arc, or a dribble?' However simple this enquiry may sound, the question of writing your name in the snow in Braille or script is readily understood by most patients, and this quick enquiry may put them at considerable comfort with the questioning provider. An affirmative response to nocturia and flow may lead one to start thinking about EP; however, it is important to ask about symptoms that may indicate other diseases and diagnoses. There are multiple causes of nocturia such as diabetes, use of diuretics or congestive heart failure. Likewise, poor flow could result from a stricture or a neurogenic bladder. Pain is not generally considered a symptom of EP, but is of prostatitis, interstitial cystitis or infection. Urgency could be as a result of EP, but it is also a symptom of overactive bladder. It is also vital to ascertain the duration of the symptoms. EP is a progressive disease and, as such, the symptoms will usually have been getting more problematic for a while. A presentation of an acute problem is more consistent with some sort of trauma or infection. Several articles have suggested an age at which to enquire about urinary function (20). Another view would be to discuss normal expected bladder habits and hygiene as soon as the patient can comprehend them. By doing this, the provider may be removing some of the mystique surrounding the urinary tract. Patients need to understand from an early age that the bladder stores and empties and they should have a good arc to their flow. Frequent urination (urgency) or poor flow are not normal, and need to be brought to the attention of the provider. This way, when symptoms occur, the patient understands opportunities exist. Unfortunately, many patients derive what they believe normal function is by what they experienced watching their fathers or grandfathers, and attribute urinary symptoms to normal ageing. Evaluation After the identification of the male with symptoms consistent with EP, it is important to conduct a focused history and physical examination, as well as a few laboratory tests. This information is crucial, as the provider is looking for significant findings that may warrant referral to a specialist (Table 1). Equally important, the provider must uncover possible reversible causes of LUTS and to identify comorbidities that could potentially complicate treatment (21). For example, poorly controlled diabetes and diuretics taken for hypertension are frequent offenders, causing frequency and irritative symptoms, but not necessarily flow or obstructive concerns. Cold medications, which may include alpha agonists, commonly cause flow problems; however, this usually presents with an acute onset, unless the patient uses these treatments chronically. Table 1. Indications for referral. Adapted with permission from Rosenberg et al. (21) Indications for referral History of recurrent urinary tract infections or other infection Microscopic or gross haematuria Prior genitourinary surgery Elevated prostate-specific antigen Abnormal prostate exam (nodules) Suspicion of neurological cause of symptoms Findings of suspicion of urinary retention Meatal stenosis History of genitourinary trauma Uncertain diagnosis Pelvic pain The physical examination in the office of the PCP can be brief and focused on a few key elements. An abdominal examination is important to evaluate tenderness, masses or bladder distention. A focused neurological examination is needed to assess general mental status, ambulatory status and motor function. A digital rectal examination (DRE) is invaluable in the evaluation of rectal tone and prostate size, consistency, nodules or pain. Abnormal findings on physical exam should be fully investigated. The needed laboratory tests are minimal and most have been probably carried out during the routine or yearly examination of the patient. A fasting or random blood sugar is essential to rule out diabetes mellitus as a cause. Assessment of renal function by measurement of serum creatinine is not uniformly recommended (22-25). It is likely that most patients will have had an evaluation of renal function; however, it is probably better to be conservative and verify that it is in the normal range. A urinalysis is essential to check for blood or infection. Haematuria warrants an immediate referral for evaluation of urological malignancy. It is not appropriate to use the urinalysis to rule out the possibility of diabetes (as opposed to a blood draw) as the serum blood sugar must be over 180 mg/dl before glucose is spilled into the urine (21). There is significant controversy surrounding the use of the prostate-specific antigen (PSA) test. Recent studies have mixed reactions with regard to its ability to assist in decreasing morbidity or mortality with regard to prostate cancer [PLCO (26); ERSPC (27)]. However, it must be remembered that the PSA is prostate specific and not cancer specific. It is a tool that allows the provider and the patient to make an educated decision regarding patient care. In 1999, Roehrborn et al. demonstrated that PSA level can correlate to the size or volume of the prostate (28). Increased size of the prostate is directly related to an increased risk of BPH progression (29). In fact, the PSA is a more accurate predictor of prostate volume then DRE (30). As emphasised by Roehrborn, a PSA value of 1.5 ng/ml, regardless of age, correlates to a prostate volume of 30 ml. This value is a key point in our decision-making process. Therefore, measuring the PSA level is essential in the evaluation of the patient with symptoms of EP, in addition to the utility for prostate cancer detection. Any abnormal PSA level or interval change necessitates consultation with a specialist, and the American Urological Association (AUA) guidelines provide a good framework for understanding abnormal PSA (22). Other diagnostic measures used in the evaluation of LUTS, such as an ultrasound, bladder scanning or the ability to check uroflow, are generally not available to the PCP. At the same time, their usage in the initial evaluation of EP may be limited. These are listed as optional by the guidelines and the evaluation of the refractory patient can be left to the specialist. Results from these investigations are not essential before the PCP considers empiric therapy. There is another purpose to the evaluation aside from ruling out other causes of the symptoms, and that is to identify the factors that may place the patient at risk for EP progression. Crawford et al. identified five risk factors after reviewing the data from the placebo arm of MTOPS. These include a total prostate volume ≥ 31 ml, PSA ≥ 1.6 ng/ml, Qmax (flow rate) < 10.6 ml/s, PVR ≥ 39 ml or age ≥ 62. As mentioned before, most PCPs will not be able to assess postvoid residual (PVR) or flow rate (Qmax). However, age and PSA are simple and volume is directly linked to PSA (29). Treatment The choice of treatment belongs to the patient after a complete explanation by the provider. A patient who is educated on the disease state is likely to stay more involved and compliant with whatever modality is chosen. As the outcome of EP is rarely dire, it is up to the patient to decide what to do and when to do it. In this context, we believe the simplified treatment of the enlarged prostate (STEP) approach presented in Figure 1 is a logical plan for managing the patient with EP. The management using this approach is not meant to be inclusive of every patient type, rather a tool to decide what may be best for the patient. It is essential to pay attention not only to outcomes but also to the 'red flag' indicators which should trigger the need for referral to the specialist (as noted in Table 1). It is important to note that groups like the AUA and European Association of Urology (EAU) have presented treatment guidelines and algorithms (22, 23). The stEP approach is an attempt to simplify these comprehensive works for the busy provider at the front-line of patient care. Figure 1Open in figure viewerPowerPoint STEP: Simplified Treatment of the Enlarged Prostate Step 1: watchful waiting In this step no medication is warranted as the patient has LUTS but no bother. Watchful waiting is recommended if symptoms are not bothersome to the patient, and he has not developed complications of BPH such as BOO, hydroureter, haematuria, hydronephrosis, AUR, UTIs, bladder hypertrophy and others (31). This approach is also chosen if the symptoms are mild according to the IPSS ≤ 7 (1). Knowing that most PCPs will be unlikely to utilise the IPSS, simply asking the patient if he is bothered by his symptoms may be sufficient. It is critical for the PCP to explain that EP is a progressive disease and emphasise that the patient should speak with his provider if symptoms worsen. Why some patients choose treatment whereas others do not is certainly an interesting issue about which one can speculate. Frequently, patients will acknowledge their symptoms and want to verify that a fatal disease is not the cause (for example, prostate cancer). It is interesting to note that men are reluctant to bring up LUTS as a result of fear that these symptoms represent a serious or life-threatening problem. An explanation from his PCP regarding the cause of his symptoms can be enlightening for the patient, as well as a source of great relief. Those patients who opt for watchful waiting may benefit from lifestyle changes. Limitation of fluids, bladder training focused on timed and complete voiding, and treatment of constipation may help patients regulate urinary symptoms. Similarly, a review of the patient's medication list will help identify opportunities to modify (change the timing of diuretics) or avoid (decongestants) medications that may impact symptoms of BPH. The downside of watchful waiting is that some patients will progress. A longitudinal study found that over a 4-year time span 87% of men with mild symptoms experienced worsening symptoms while 13% of men had symptoms that improved or remained stable (32). Watchful waiting may only delay treatment and not allow it to be avoided. Understanding the risk factors for progression of EP puts the patient and the provider at an advantage to anticipate future issues. Step 2: initiate therapy with an alpha-blocker In this step, single medication therapy is appropriate for the symptomatic patient who has identified LUTS with bother and has a PSA of < 1.5 ng/ml. Initiating treatment α-blocker (AB) has been an option for many years. The currently recommended medications include the non-selective second generation ABs (doxazosin and terazosin) and uroselective third generation ABs (alfuzosin, tamsulosin, silodosin). By inhibiting α1-adrenergic-mediated contraction of prostatic smooth muscle, AB therapy relieves the bladder outlet obstruction (22). For many men, this is sufficient for satisfactory relief of symptoms. Patients with smaller prostates (< 30 ml) tend to benefit the most from this monotherapy (29). Treatment failure with ABs is higher in men with larger prostate volumes (34). The AB class of medications works quickly, usually within the first week of therapy, to relieve symptoms. It is important for the patient and the provider to note that while ABs improve symptoms, they do not affect the progression of prostate growth. These medications do not result in long-term reduction in the risk of AUR or BPH-related surgery (30). Common side effects reported with AB therapy include orthostatic hypotension, dizziness, tiredness, ejaculatory problems and nasal congestion (22). The uroselective ABs seem to have fewer side effects than the non-selective one; however, they can be associated with lightheadedness and ejaculatory dysfunction. Step 3: initiate therapy with an alpha-blocker and a 5-alpha reductase inhibitor In this step, combination therapy with an AB and 5ARI is appropriate for the symptomatic patient with LUTS who has identified bother and a PSA of 1.5 ng/ml or greater. For some patients, treating the dynamic component of EP with an AB is not enough and may delay treatment of a progressive condition. A common goal of therapy in these patients is to treat the progression by reducing the static component of the enlarged gland. In the evaluation section, we identified the five areas identifying the patient at risk of disease progression as PSA, size, age, flow and PVR. Now the question centres on the ability of the PCP to stratify risk by attaining this information. As one critically evaluates these factors, we can come to a few logical conclusions. As PSA is a surrogate marker for size, we do not need the volume as ascertained by the educated and experienced DRE or prostate ultrasound. Age is an easy one. Flow and PVR, however, present a problem in the setting of a primary care office. However, does this information really help in the initial evaluation and treatment of EP? If a patient describes a weak flow, we can reason that he understands what a good flow is and that the present situation is different. Further, would the actual flow value alter therapy? Rationally, this data point would not change initial therapy. Likewise, would knowledge of the PVR volume change the initial therapy? Whether it is high or low, the provider is still going to treat the likely cause of the patient's symptoms: EP (21). True, the occasional patient with severe retention may filter through, but at what consequence? If he responds, the provider has helped him. If he does not respond, he should be referred to a urologist for further evaluation. An empiric trial of therapy for the patient at risk for progressive disease should not have a negative consequence on the patient except for a minor loss of time. Therefore, given no other signs of an obstructive uropathy, the choice of treatment does not hinge on the informa