Lower urinary tract symptoms in men are a major problem for older men, and there are many treatments available for lower urinary tract symptoms, including medications and surgical treatments, and even botanical extracts. However, each method has its own advantages and disadvantages, and is suitable for different groups of people. An article by Drs. Hollingsworth and Wilt in the BMJ summarizes the treatment options for lower urinary tract symptoms secondary to BPH, published on August 14 and compiled below.
I. Introduction
Benign prostatic hyperplasia (BPH) is originally a histological diagnosis that refers to benign hyperplasia of prostate cells. By age 70, nearly 70% of the population will have histologic BPH. about half of the population will develop an enlarged prostate, and half of these (17% of the total) will have associated bladder outlet obstruction and lower urinary tract symptoms. In the United States, the direct medical costs of treating prostate enlargement, in addition to the cost of medications, exceed $1 billion annually, and this number is rising.
BPH is the most common and costly condition in older men, and the associated lower urinary tract symptoms significantly affect quality of life. In addition, lower urinary tract symptoms, especially nocturia, increase the risk of falls and fractures. Therefore, the main goals of treatment are to reduce troublesome lower urinary tract symptoms and to prevent disease progression (e.g., to acute urinary retention).
In the past, the only treatment for LUTS was surgery and was limited to severe symptoms such as acute urinary retention, and sequelae of bladder outlet obstruction such as renal insufficiency and recurrent urinary tract infections. However, with the introduction of effective medications, patients with milder symptoms can benefit from diagnosis and treatment, so it is more appropriate to consider lower urinary tract symptoms as a chronic condition. Lifestyle changes and medications have become a major part of the initial treatment of lower urinary tract symptoms.
With this change in treatment, the role of the primary care physician in the management of patients with BPH has become even more important. More than 2/3 of primary care patients are seen by primary care physicians. The purpose of this review is to summarize the literature on BPH-related lower urinary tract symptoms with the goal of improving patient care.
II. Prevalence of BPH
One of the challenges in studying the epidemiology of BPH is our current lack of consensus on the diagnosis of the disease. As mentioned above, the diagnosis of BPH includes a histologic evaluation. Several studies have used pathologic biopsies to determine the prevalence of BPH. In the last 40 years, only 8% of men have been biopsied, but this has increased to 50% in men aged 51-60 years. The prevalence of histologic BPH is similar in the United States, Europe, and Asia.
Although a maximum urinary flow rate greater than 20 ml/s is considered statistically “normal,” data from the Olmsted County study showed that 6% of men aged 40 to 44 years had a maximum urinary flow rate less than 10 ml/s, increasing to 35% of men after age 75 years. Some cohort studies have reported a 1.6% annual increase in prostate size, so that the median prostate volume in men older than 50 years is greater than 40 ml.
Patient self-reporting provides a more clinically relevant assessment of the prevalence of BPH in studies. By and large, the more severe the lower urinary tract symptoms, the greater the impact on the patient’s quality of life and the greater the patient’s desire to seek care. Using a validated urinary tract symptom scale, 13% of men aged 40 to 49 years and 28% of men older than 70 years in the Olmsted County study had moderate to severe lower urinary tract symptoms. It is important to note that prevalence estimates are based on the cut-off value of the symptom scale, and if this cut-off value is changed the prevalence will change significantly.
In addition, although lower urinary tract symptoms are related to urinary flow and prostate volume, there is substantial evidence that men can develop lower urinary tract symptoms even in the absence of BPH/prostate enlargement or abnormal urinary flow. This is partly because lower urinary tract symptoms are caused by a variety of factors, including prostate and bladder smooth muscle tone and contractility.
Moreover, the prevalence of lower urinary tract symptoms in women is not very different from the prevalence in men. Therefore, although lower urinary tract symptoms in older men are usually the result of BPH, clinicians should identify and evaluate other causes (e.g., neurogenic bladder dysfunction, medication-induced lower urinary tract symptoms, and nocturia due to cardiac disease).
Diagnosis and evaluation
The diagnosis of BPH is based on the clinical features: enlarged prostate, lower urinary tract symptoms, and the exclusion of other causes of urinary tract symptoms. Most primary care physicians make the diagnosis based on the patient’s complaints of voiding symptoms (including dysuria, intermittent urination, thin urine stream, and hesitancy to urinate) or storage symptoms (frequency, urgency, and nocturia), as well as possible enlargement of the prostate on rectal examination.
It is important to note that nocturia is an important factor that affects the patient and is a significant factor in the patient’s visit. Urinalysis can help detect curable conditions that cause these symptoms (e.g., urinary tract infections).
If the diagnosis of BPH is uncertain and a tumor is suspected, prostate-specific antigen (PSA) can be used as a screening test. Although patients and physicians are concerned that prostate cancer is the cause of lower urinary tract symptoms, BPH is not a risk factor for prostate cancer. Therefore, in patients with typical lower urinary tract symptoms, PSA measurement in primary care treatment should be viewed more as a screening test than as a diagnostic evaluation.
In addition, an enlarged prostate can elevate PSA levels, reducing diagnostic specificity. These limitations should be taken into account when testing for diagnosis. There are no organizations or guidelines that recommend the use of PSA testing for patients older than 70 years of age or with limited life expectancy.
Risk factors
Age is a major risk factor for BPH, and it is not clear whether BPH is associated with family history. A number of other factors may be associated with the development and progression of the disease, such as metabolic disorders. In particular, data from the American Health Professions Follow-up Study suggest a high association between obesity and lower urinary tract symptoms. This finding was confirmed by two population-based studies in China and Norway, respectively. Furthermore, data from the Baltimore Longitudinal Study of Aging suggest a greater preponderance of enlarged prostate in obese men.
Type 2 diabetes may also be a risk factor for BPH. In addition to diabetes-induced urinary frequency, insulin can bind to the insulin-like growth factor receptor (IGFR), activating the receptor and thereby mediating prostate cell growth and proliferation. A community study in Massachusetts found that people with type 2 diabetes were 50% more likely to have clinical BPH than the general population, even when weight was taken into account. In addition, a Swedish cohort study showed that diabetics had the largest median prostate.
Unlike obesity and diabetes, exercise may have a protective effect on BPH. Chronic moderate exercise reduces sympathetic nerve activity at rest and decreases agonism of sympathoadrenergic neurons. This may contribute to less prostate smooth muscle tone. Studies have shown that increased exercise is associated with a reduced risk of lower urinary tract symptoms, independent of weight control. The Massachusetts Male Aging Study had similar findings, concluding that increased exercise habits in men were associated with a reduced risk of clinical BPH.
V. Initial assessment and treatment management
The severity of symptoms and the degree of voiding distress determine the initial assessment and treatment. Reliable symptom and distress index scales are more commonly used in urologic practice and research. The most common are the American Urological Association symptom indexc (AUASI) and the International Prostate Symptom Score (IPSS, interactive IPSS calculation and strategies website attached to the original article http://bit, do/bmj-luts).
Both scales include a 7-item questionnaire that assesses the presence of voiding and storing symptoms, and their severity. Scores ranged from 0 to 35, with scores above 7 being considered as moderate symptoms and above 19 as severe symptoms. A clinically significant score of at least 3 is required.
Although the use of these questionnaires is recommended, their application in primary health care is not necessarily feasible. However, it is important to at least briefly assess the degree to which the patient’s symptoms bother them (none, mild, moderate, severe), as these assessments correlate with the severity of symptoms and influence treatment decisions. Patients affected by moderate to severe urinary tract symptoms are more likely to benefit from pharmacologic and surgical interventions.
For patients with mild symptoms, counseling and lifestyle changes are more acceptable in the first place. However, it is important to inform the patient that these symptoms do not increase his risk of developing cancer and to allay his concerns. In addition, regular urination, avoiding caffeine and alcohol, adjusting the dose of diuretics and reducing fluid intake (especially in the evening) are effective measures for many patients.
A randomized controlled clinical trial showed that patients with uncomplicated lower urinary tract symptoms had a 48% reduction in treatment failure (e.g., initial medication) after 12 months of self-management training compared to patients who were observed alone.
VI. Drug therapy
1. α-receptor antagonists
For patients with moderate to severe symptoms, alpha receptor antagonists can improve symptoms and reduce symptom distress. alpha receptor antagonists inhibit prostate tissue contraction by binding to alpha1 receptors in prostate smooth muscle. alpha1 receptors have three subtypes (alpha1a, alpha1b, and alpha1d), but only alpha1a type can modulate prostate smooth muscle tone. Because α1 and α2 receptors are also expressed in the bladder base and proximal urethra, α receptor antagonists may reduce bladder outlet resistance due to urinary tract smooth muscle.
Approximately 60% of patients treated with alpha antagonists have reduced urinary tract symptoms after one month of therapy. The short duration of action of alpha antagonists and their effectiveness in a large proportion of the population is one reason why they are commonly used for lower urinary tract symptoms.
Another reason is that its action is not related to prostate size. In patients who respond to alpha antagonists, the drugs work for several years and are well tolerated. However, long-term clinical trials have shown that these drugs do not reduce the probability of surgical intervention, nor do they reduce the risk of progression of the disease to acute urinary tract obstruction.
2. Phenoxybenzamine
Phenoxybenzamine is a non-selective, long-acting receptor antagonist, and it was the first effective alpha receptor antagonist for the treatment of BPH-related lower urinary tract symptoms. However, its use is currently limited due to the presence of a high number of side effects.
3. Terazosin and doxazosin
Terazosin and doxazosin are the first generation of long-acting drugs for the treatment of lower urinary tract symptoms. Multicenter clinical trials have shown that patients using these drugs report significant improvement in their symptoms compared to placebo. However, treatment with terazosin and doxazosin needs to be started with slow dose increases to avoid sudden and sometimes severe drops in blood pressure when there is a shift from a prone to a standing position. Other common side effects include abnormal ejaculation, weakness and dizziness.
4. Tamsulosin
Tamsulosin is the first highly selective alpha1 receptor antagonist. Similar to the gastrointestinal controlled release of doxazosin, tamsulosin does not require slow dosing. Large phase III clinical trials have shown that tamsulosin significantly improves lower urinary tract symptoms and peak flow rates and is generally well tolerated by patients. Compared to other alpha antagonists (terazosin), tamsulosin increased peak flow rates and significantly improved symptom scores. However, patients using tamsulosin appear to be less likely to discontinue treatment for other reasons than terazosin.
5. Alfuzosin
Alfuzosin is a second-generation selective alpha1 receptor antagonist. Similar to tamsulosin and doxazosin controlled-release agents, alfuzosin does not require slow dosing. According to Pooled Analysis of three randomized controlled trials, alfuzosin significantly reduced symptom scores and increased urinary flow rates. In terms of efficacy and side effects, alfuzosin and tamsulosin are comparable.
6. Silodosin
Silodosin is the newest selective α1a receptor antagonist. Its durability of symptom relief is comparable to that of tamsulosin. A potential advantage of silodosin is that it is better tolerated by the heart than alfuzosin. The data suggest that silodosin does not prolong the QT interval, thereby reducing the incidence of arrhythmias. However, studies have shown that it can increase the risk of retrograde ejaculation and that dose adjustment is required in patients with renal insufficiency.
One of the side effects of alpha-adrenoceptor antagonists is related to its pupil-dilating effects. More than 40% of patients using tamsulosin develop iris relaxation and swelling, iris detachment from the surgical incision, and progression to intraoperative pupillary constriction during cataract surgery. Although intraoperative iris relaxation syndrome is primarily associated with tamsulosin, it also occurs with other drugs such as terazosin, doxazosin, and alfuzosin.
These symptoms can lead to surgical complications (iris damage in half of cases) and the ophthalmologist should be prepared to change the procedure for patients who are taking alpha receptor antagonists, but this will increase the difficulty of the procedure and the cost to the patient.
7. 5α reductase inhibitors
5α-reductase inhibitors are the next most common drug used to treat BPH-related lower urinary tract symptoms. Unlike alpha-adrenoceptor antagonists, 5α-reductase inhibitors do not alter the tone of the prostate smooth muscle. 5α-reductase inhibitors shrink the prostate and reduce the associated bladder outlet obstruction by blocking the conversion of testosterone to dihydrotestosterone. The rationale behind this is that the development of BPH has been observed to be androgen dependent. More specifically, surgical debulking and gonadotropin-releasing hormone analogs can reduce prostate volume.
8. Finasteride and dutasteride
Finasteride inhibits type 2 5α-reductase and is the first 5α-reductase inhibitor for BPH. In a randomized clinical trial with a sample of 3040 subjects taking 5 mg of finasteride or placebo for 1 year, finasteride was found to reduce acute urinary retention by 57% and BPH surgery by 55%. However, in another randomized clinical trial comparing finasteride to alpha antagonists, it was found that although finasteride reduced prostate volume by 20%, finasteride was not as effective as terazosin, nor was it more effective than placebo in improving urinary symptoms and urinary flow rates.
Dutasteride is the newest 5α reductase inhibitor, which inhibits both type 1 and type 2 5α reductases. Similar to finasteride, dutasteride reduces the risk of acute urinary retention and BPH-related surgery in patients with moderate to severe disease.
There are no studies comparing finasteride and dutasteride. Observational studies suggest that dutasteride reduces symptom scores more significantly and shows clinical improvement more quickly (within 3 months) than finasteride, which may be related to its simultaneous inhibition of both type 1 and type 2 5α reductase effects. However, multicenter randomized double-blind clinical trials have shown similar efficacy of dutasteride and finasteride in improving symptom scores in patients with enlarged prostates after 12 months of daily dosing.
5 alpha reductase inhibitors can cause decreased libido, decreased ejaculation and gynecomastia, but are well tolerated by most people.
In addition to improving lower urinary tract symptoms, 2 large placebo randomized controlled trials have shown that finasteride and dutasteride reduce the risk of prostate cancer by 23% to 25%. However, 5α-reductase inhibitors can increase the risk of high-grade prostate cancer. Although this increased risk may be due to histological errors caused by prostate shrinkage, in 2011 the FDA warned of the risk of high-grade prostate cancer with 5α-reductase inhibitors.
Therefore, these drugs should not be used for prostate cancer prevention. If 5α-reductase inhibitors are to be used, clinicians should discuss this information with patients, even if the treatment is not intended to prevent prostate cancer.
9. Combination of an alpha receptor antagonist and a 5 alpha reductase inhibitor
The Veterans Collaborative Study examined whether the combination of an alpha receptor antagonist and a 5 alpha reductase inhibitor could have additional benefits. This multicenter study randomized 1229 veterans to placebo, terazosin, finasteride, and a combination of terazosin and finasteride. After a 52-week follow-up period, it was found that the combination was significantly better than placebo and finasteride alone in terms of symptom scores. However, the effect of the combination was not superior to terazosin alone in terms of symptom scores. European prospective doxazosin and combination therapy clinical trials had similar results.
Since the focus of the previous studies was on the short-term effects of drug combinations, the Prostate Symptom Treatment trial was designed to examine the long-term effects of combination therapy, particularly in terms of the risk of clinical progression. Clinical progression in this context is defined as an AUASI score of greater than or equal to 4, the need for surgical treatment or progression to acute urinary retention. In this 6-year multicenter randomized clinical trial, 3047 patients with moderate to severe lower urinary tract symptoms (mean AUASI of 16, 9) received placebo, doxazosin, finasteride, and combination therapy.
After a mean follow-up period of 4 and 5 years, the overall risk of progression was reduced by 66% in combination-treated patients compared with placebo-treated patients. Although combination therapy reduced the risk of surgical treatment and acute urinary retention, the most significant benefit for patients was a reduced rate of symptom progression. These same risks were reduced compared to doxazosin or finasteride alone. A reanalysis of this study suggests that prostate volume (greater than 25 ml) may predict whether patients will benefit from combination therapy.
To explore the importance of prostate size on treatment response, the researchers designed a clinical trial of the combination of Aodart (dutasteride) and tamsulosin. After a 4-year follow-up period, patients treated with the combination had significantly lower urinary storage symptom scores than those treated with dutasteride or tamsulosin alone, with similar results for urinary symptom scores.
A recent systematic evaluation assessed combination therapy (alpha receptor antagonists and 5α reductase inhibitors) for men with non-neurogenic lower urinary tract symptoms, from which the authors concluded that patients with prostates in the 30-40 ml range could benefit from the combination therapy if treated for >1 year.
10. Antimuscarinic drugs
The symptoms of the storage phase are caused by obstruction of the bladder outlet due to an enlarged prostate, or by obstruction due to other causes in the bladder itself. In the latter case, treatment directed at the prostate may not relieve the symptoms of urinary urgency and may increase the frequency of daytime urination. This is the hidden rationale behind the use of antimuscarinic drugs (alone or in combination with alpha receptor antagonists).
Acetylcholine binds to receptors and the bladder muscles contract; antimuscarinic drugs work by blocking muscarinic receptors on the muscarinic muscle and the urinary tract epithelium.
Many studies have examined the efficacy of antimuscarinic drugs (alone or in combination with alpha receptor antagonists) on urinary storage symptoms, with the most definitive data coming from a study of 879 patients. Eighty percent of patients receiving tolterodine and tamsulosin extended release improved after 12 weeks of treatment, compared with 62% with placebo, 71% with tamsulosin alone, and 65% with tolterodine alone (all statistically significant).
One of the concerns with the use of antimuscarinic drugs in patients with lower urinary tract symptoms is that it may exacerbate voiding phase symptoms. The most recent systematic evaluation and meta-analysis of these issues. A pooled analysis of placebo controls found that the combination showed a slight decrease in maximum urinary flow rate and residual urine volume and a small increase in the risk of acute urinary retention compared with alpha receptor antagonists alone. Therefore, the addition of an antimuscarinic agent along with an α-receptor antagonist may be an option for patients with persistent storage phase symptoms, and monitoring of residual urine volume is recommended.
11. 5 Phosphodiesterase inhibitors
Tadalafil is the latest drug approved for the treatment of lower urinary tract symptoms associated with BPH. Tadalafil acts on phosphodiesterase 5 and is commonly used to assist with erections, while studies say 55% to 50% of patients with mild to moderate lower urinary tract symptoms have erectile dysfunction. Lower urinary tract symptoms and erectile dysfunction have some common links (e.g., NO-cGMP pathway) that may be targets for phosphodiesterase 5 inhibitors, but the link between the two remains unclear. Furthermore, phosphodiesterase 5 is highly expressed in the bladder neck, urethral prostate, and prostate tissue.
There are currently seven clinical trials comparing the effects of 5 phosphodiesterase inhibitors with placebo in patients with both moderate to severe lower urinary tract symptoms and erectile dysfunction, and a recent meta-analysis summarizes these results. The results showed that after a 12-week follow-up period,5 phosphodiesterase inhibitors reduced the severity of lower urinary tract symptoms compared with placebo, with no significant difference in urinary flow rate.
However, data on the long-term effects of the drug are still lacking. Routine use of 5 phosphodiesterase inhibitors improved sexual function in patients. Side effects were approximately 16% and included facial redness, headache, and sinusitis.
Table-1 Pharmacologic treatment of lower urinary tract symptoms secondary to BPH
Drug Use Dose Follow-up Time Effectiveness Side Effects alpha receptor antagonist Non-selective 2 to 4 weeks AUASI score improved over placebo (38% vs 17%) Maximal urinary flow rate improved over placebo (22% vs 11%) Dizziness, postural hypotension, malaise, nasal congestion, abnormal ejaculation, impotence Alfuzosin extended release 10 mg qd Doxazosin 1 mg qd Slowly increasing dose (maximum amount (8 mg) Terazosin 1 mg qd Slow dosing (maximum amount 20 mg) Selective Cilodosin 8 mg qd Tamsulosin 0,4-0,8 mg qd5α reductase inhibitor 3 to 6 months Monotherapy reduced risk of BPH surgery by 55% and urinary retention by 57% compared with placebo Decreased libido, decreased ejaculation, gynecomastia Dutasteride 0,5 mg qd Finasteride 5 mg qd antimuscarinic drugs for 6-12 weeks Significant reduction in IPSS storage phase symptom scores compared to alpha receptor antagonists; combination with alpha receptor antagonists reduced dry mouth, constipation, drowsiness, blurred vision, dyspepsia, urinary retention Non-selective Fexorodine 4-8 mg qd oxybutynin extended release 5-10 mg qd tolterodine extended release 2-4 mg qd Trasylol 20 mg bidM3 receptor selective Dafinacin extended release 7, 5-15 mg qd Solifenacin 5-10 mg qd5 phosphodiesterase inhibitors 4-8 weeks IPSS and IIEF significantly improved headache, dizziness, flushing, dyspepsia, nasal congestion or rhinitis Tadalafil 2, 5-5 mg qd
12. Phytotherapy
1/3 of patients who chose not to undergo surgical treatment initially used botanicals, alone or in combination with prescribed medications. Although there are more than 30 botanicals on the market for the treatment of BPH symptoms, American saw palmetto (Saw Palmetto) extract is the most commonly used one.
A systematic analysis in 1998 suggested that saw palmetto extracts may mildly improve symptoms. The incidence of side effects (such as diarrhea, loss of libido, and ejaculation disorders) was comparable to placebo. However, few studies have reported its hepatic or pancreatic toxicity.
From 1998 to the present, there are more and more rigorous studies on saw palmetto. The Saw Palmetto for Enlarged Prostate clinical trial included 225 patients with moderate to severe lower urinary tract symptoms. After a 1-year follow-up period, there were no statistical differences in symptom scores or secondary endpoints between the two groups.
More recently, another large study showed that increasing doses of saw palmetto fruit extract did not reduce symptoms or other outcomes due to BPH. An update of the systematic study (which included both studies) concluded that saw palmetto did not improve lower urinary tract symptoms, nor did increasing to a 2-fold or 3-fold dose.
VII. Surgery
In patients with moderate to severe lower urinary tract symptoms that do not resolve with medication, referral to a specialist for consideration of surgical treatment is appropriate. A urologic consultation is also recommended for recurrent urinary tract infections secondary to BPH, sarcoid hematuria, bladder stones, or renal insufficiency. Because of the high failure rate of BPH surgery in the absence of evidence of lower urinary tract symptoms due to bladder outlet obstruction, the urologist will perform additional tests prior to surgery.
Pressure/urinary flow rate measurements are the gold standard for bladder outlet obstruction and are diagnostic based on a maximum urinary flow rate of less than 12 ml/s and a forced urinary muscle pressure greater than 20 cm H2O at maximum flow rate. However, patient acceptability is an issue due to the complications associated with these tests and the cost. Therefore, attempts have been made to diagnose bladder outlet obstruction by noninvasive methods, but neither ultrasound detection of residual urine volume nor prostate volume has good sensitivity.
However, detection of bladder wall thickness and bladder weight are promising methods. In some cases where the maximum urinary flow rate is less than 10 ml/s and a moderate volume of urine can be excreted, urodynamic testing alone is sufficient.
1. Transurethral electroporation of the prostate
If the patient does not have an associated bladder outlet obstruction and surgery is the treatment of choice, the urologist should discuss with the patient the risks and benefits of the many different procedures. For nearly half a century, transurethral resection of the prostate (TURP) has been the standard procedure for the surgical treatment of BPH, using a monopolar electric knife to remove the prostate gland through an endoscope. Although TURP is effective and provides more durable relief of lower urinary tract symptoms (an average decrease in symptom scores of 10 to 18 points at 16 months), it also carries some risks.
In particular, dilutional hyponatremia is a high-risk complication of TURP, resulting from hemodilution due to the absorption of intraoperative flushing fluid into the bloodstream. The current incidence of these so-called TURP syndromes ranges from 0.8% to 1.4%. Other complications include erectile dysfunction (5%), bladder neck contracture, need for blood transfusion, urinary tract infection, and hematuria. Bipolar electrodes can reduce some of these complications, but more advanced procedures are available (see discussion below), some of which do not require general anesthesia, have fewer side effects, and can be performed on an outpatient basis.
2. Minimally invasive procedures
(1) Transurethral needle ablation (TUNA)
TUNA applies low levels of radiofrequency energy to the prostate tissue to selectively cause cellular necrosis. A recent systematic review comparing the advantages and disadvantages of TUNA and TURP showed that although TUNA significantly improved patients’ symptom scores and quality of life, it was not as effective as TURP, which increased the maximum urinary flow rate and reduced the amount of residual urine. Moreover, the long-term effect of TUNA was diminishing, with a significantly higher rate of re-treatment than TURP (10% vs. 1%).
(2) Transurethral microwave thermotherapy (TUMT)
Transurethral microwave thermotherapy heats the prostate tissue to 45-60°C, causing cell necrosis. Pooled analyses have found that TUMT can be an effective alternative option to alpha receptor antagonists in patients without a history of urinary retention or prostate surgery. Compared to terazosin, patients treated with TUMT had more significant symptom relief. However, TURP is associated with better symptom scores and urinary flow rates, as well as less re-treatment than TUMT.
(3) Prostatic urethral lift (PUL)
Other minimally invasive procedures have been developed that allow more tissue to be preserved, and one of the more promising is the PUL, which consists of an embedded suture through the urethra that is guided by a cystoscope to support each lobe of the prostate. A retrospective analysis by the National Institute for Health Care Quality Standards in the UK suggests that PUL is safe and effective for treating lower urinary tract symptoms. However, case selection is important and PUL is not a substitute for surgery.
(4) Laser prostatectomy
To reduce surgical treatment, many laser treatments have been developed, the first being visible laser ablation of the prostate. It was soon not used anymore because patients often had distant difficulty in urination and urinary retention after the procedure.
Holmium laser followed. It has a wavelength that can penetrate tissue less than 500 μm thick and is readily absorbed by water. Although the holmium laser can be used to vaporize tissue, it is more commonly used to enucleate the prostate.
Photoselective vaporization of the prostate has also been described. This method is based on the energy of the titanium phosphate laser, which has a wavelength in the green visible spectrum. The newest laser used for the procedure is the thulium laser. The laser wavelength is adjustable between 1.75 μm and 2.22 μm, so that intraoperative vaporization or cutting of the tissue can be chosen.
Holmium, titanium phosphate and thulium lasers improve symptoms and quality of life to the same extent as TURP. Compared to TURP, laser treatment results in less intraoperative blood loss and therefore fewer postoperative hospital days for patients. The laser has good hemostasis, so intraoperative and postoperative flushing may be reduced, maintaining hemoglobin concentrations and therefore providing additional benefit to patients who are taking anticoagulants or have heart/kidney disease.
Analysis of national health insurance data reflects the increasing use of these new treatments. From 1999 to 2005, BPH surgery increased by 44%, and minimally invasive procedures (TUNA and TUMT) and laser surgery increased by 529% over the same period. Overall, 57% of BPH surgeries were performed, while traditional TURP accounted for only 39%. Nearly all TUMT and 86% of TUNA are performed in the clinic, and more than one-third of laser procedures are performed in the outpatient setting.
VIII. Outlook
1. Botulinum neurotoxin A
For drug-insensitive lower urinary tract symptoms secondary to BPH, botulinum neurotoxin A has not been considered as an alternative treatment to surgery until recently. In urology, botulinum neurotoxin A has many indications for use, including the treatment of neurogenic and primary detrusor overactivity. When injected intraprosthetically, it induces apoptosis of prostate cells, leading to prostate atrophy and volume reduction; inhibits prostatic sensory neurons and reduces afferent signals to the central nervous system; and relaxes prostate smooth muscle cells.
Most botulinum toxin A injection therapies are non-experimental. A randomized, double-blind, randomized, placebo-controlled trial suggested that Botox A improved symptoms and urinary flow rates, as well as residual urine volume and prostate volume (saline control). Encouraged by these findings, Allergan conducted a large clinical trial. However, the results found that Botox was no more effective than placebo injections. Botulinum toxin A treats the development of intractable lower urinary tract symptoms therefore the middle section.
2. Drugs that inhibit fibrosis
Fibrosis may be another target for the treatment of lower urinary tract symptoms. Studies have concluded that fibrosis is the leading cause of death in chronic inflammation. A portion of prostate histology studies point to the presence of chronic inflammation in the prostate and suggest that chronic inflammation promotes the development of lower urinary tract symptoms. It is important to note that in patients with moderate to severe lower urinary tract symptoms, there is an increased collagen component of the prostate, inflammatory cells and fibroblasts at high levels, increased tissue stiffness, as well as reduced levels of elastic fibers and periurethral prostatic glandular features.
Therefore, anti-fibrotic drugs may work in patients who do not respond to medications, are intolerant, or become recalcitrant to medication. Transforming growth factor beta 1 (TGFβ1) is a multifunctional cytokine with multiple regulatory activities, including cell proliferation, migration, inflammation, and fibrosis.
Since TGFβ1 plays a central role in fibrosis, antagonists of TGFβ1 would be potential drug candidates. Many large and small molecule drugs that inhibit TGFβ1 are currently in clinical trials in some patients with fibrotic disease and potentially in the future in patients with lower urinary tract symptoms.
3. Guidelines
The AUA and EAU already have guidelines for BPH. For patients with complex lower urinary tract symptoms (suspicious rectal exam, hematuria, PSA abnormalities, dysuria, recurrent urinary tract infections, palpable bladder, or neurogenic disease), the guidelines recommend consultation with a urologist who can perform some of the guideline recommendations as basic treatment and evaluate them.
In patients with uncomplicated lower urinary tract symptoms that cause little or no personal distress, only patient education, reconfirmation that the tumor is not the cause of these symptoms, and periodic review are needed.
For uncomplicated lower urinary tract symptoms that cause more distress, the AUA recommends screening for polyuria (≥3L/24h) via the frequency-urine meter. If polyuria is present, fluid intake should be restricted (target urine output of 1L/24h). Nocturnal polyuria as the main sign (nocturnal urine output >33% of daily urine output) also requires restriction of water intake and consideration of conditions other than BPH (e.g., obstructive sleep apnea). Patients can be prescribed medications for BPH (see table), as well as other treatments such as desmopressin.
Uncomplicated lower urinary tract symptoms that cause distress to patients without polyuria require the clinician to consider a number of modifiable factors, including medication use (e.g., diuretics) and some behaviors (e.g., physical inactivity, alcohol abuse, and consumption of stimulant foods). Patients should be advised to empty their bladders before sleep, long trips and meetings. If medication is required, the AUA and EAU recommend monitoring and evaluating patients for treatment effectiveness and side effects. Assessment of response to treatment is determined by the medication used (see Table 1).
Annual follow-up is recommended for patients who are effectively treated. Patients who are not responding to treatment or whose symptoms are progressing need to be referred.
IX. Conclusion
Lower urinary tract symptoms are common in older men. These symptoms are usually distressing and reduce the quality of life of patients. By controlling symptoms, most patients can regain confidence and improve their symptoms.
For patients with mild to moderate symptoms, lifestyle changes are sufficient. For patients who fail to respond to conservative treatment, alpha receptor antagonists and 5 alpha reductase inhibitors (especially in patients with an enlarged prostate) or in combination with antimuscarinic drugs can improve symptoms within 1 to 3 months. In addition, pharmacologic treatment can slow the long-term progression of the disease (combination of alpha blockers and 5 alpha reductase inhibitors), including acute urinary retention.
Surgery and minimally invasive procedures can make treatment more effective and durable. Surgery is mainly indicated for severe symptoms and inadequate response to drug therapy. There is no evidence that an increase in residual urine volume affects the outcome of treatment. Additional investigations, such as detailed physical and neurological examinations, PSA and urodynamic tests, are rarely used in primary care treatment. However, these tests may provide patients with a more valuable treatment approach. Case.