Benign prostatic hyperplasia (BPH) is one of the most common benign diseases causing urinary disturbances in middle-aged and older men. The main manifestations are histologic enlargement of the interstitial and glandular components of the prostate, anatomic enlargement of the prostate, clinical symptoms dominated by lower urinary tract symptoms (LUTS), and urodynamic bladder outlet obstruction (BOO).
The incidence of histologic BPH increases with age, usually occurring initially after age 40 years, to >50% by age 60 years, and up to 83% by age 80 years. Similar to the histologic presentation, symptoms such as dyspareunia increase with age. Approximately 50% of men with a histologic diagnosis of BPH have moderate to severe lower urinary tract symptoms. Some studies have shown that it appears that Asians are more likely to have moderate-to-severe BPH-related symptoms than Americans.
Two important conditions must be present for BPH to occur: advancing age and a functioning testis. Domestic scholars investigated 26 elderly Qing dynasty eunuchs and found that 21 had completely inaccessible or significantly atrophied prostates. However, the specific mechanism by which BPH occurs is unclear and may be caused by a balanced disruption of epithelial and mesenchymal cell proliferation and apoptosis. Associated factors are: androgens and their interaction with estrogens, prostatic mesenchymal-adenoepithelial cell interactions, growth factors, inflammatory cells, neurotransmitters and genetic factors.
Prostatic hyperplasia leads to prolongation, pressure deformation and narrowing of the posterior urethra and increased urethral resistance, resulting in a series of changes in bladder function and the upper urinary tract. Due to the increase in bladder pressure, compensatory hypertrophy of the bladder forcing muscle, instability of the forcing muscle and reduced bladder compliance occur; if the obstruction is not lifted for a long time, the forcing muscle loses its compensatory capacity. The thickening of the bladder forceps can make the ureteral bladder wall segment lengthen and stiffen, leading to mechanical obstruction of the ureter; after the loss of bladder compensation, the ureteral bladder wall segment can be shortened again, and coupled with the increase in bladder pressure, ureteral reflux can occur, eventually leading to hydronephrosis and renal function impairment.
The first thing that should be considered is the possibility of prostatic hyperplasia (BPH) in male patients over 50 years of age who present with the following urinary tract symptoms. In order to make a definite diagnosis, the following clinical evaluation is required.
1. Medical history inquiry
(1) Characteristics, duration and concomitant symptoms of lower urinary tract symptoms
(2) History of surgery, trauma, especially pelvic surgery or trauma
(3) Past history and sexually transmitted diseases, diabetes mellitus, neurological diseases
(4) medication history, whether current or recent medications affecting bladder outlet function
(5) general condition
(6) International Prostate Symptom Score (I-PSS)
The I-PSS scale is now internationally recognized as the best means of determining the severity of BPH symptoms.
The I-PSS score is a subjective reflection of the severity of lower urinary tract symptoms in patients with BPH, and it does not correlate significantly with maximum urinary flow rate, residual urine volume, or prostate volume.
The I-PSS score patient classification is as follows: (total score 0-35)
Mild symptoms 0-7 points
Moderate symptoms 8-19 points
Severe symptoms 20-35 points
(7) Quality of life score (QOL)
The QOL score (0-6) is to understand the patient’s subjective perception of their current level of lower urinary tract symptoms accompanying them throughout their life. It is mainly concerned with the extent to which BPH patients suffer from lower urinary tract symptoms and whether they can tolerate them, hence the name distress score.
Although the above two scores cannot fully summarize the impact of lower urinary tract symptoms on the quality of life of BPH patients, they provide a platform for communication between the physician and the patient and enable the physician to have a good understanding of the disease status.
2.Physical examination
(1) Rectal examination
Rectal examination is very important for patients with lower urinary tract symptoms and should be performed after bladder emptying.
It can help to understand whether there is prostate cancer.
The clinical study by foreign scholars confirmed that 26-34% of patients with suspected abnormalities in rectal examination were finally diagnosed with prostate cancer. Moreover, its positive rate tends to increase with age. It can reveal the size, shape, texture, presence of nodules and pressure pain of the prostate, whether the central sulcus becomes shallow or disappears, and the tension of the anal sphincter. Rectal palpation is not accurate enough to determine the volume of the prostate. Currently, transabdominal ultrasound or transrectal ultrasound can describe the morphology and volume of the prostate more accurately.
(2) Local neurological examination (including motor and sensory).
3. Urine Routine
Urine routine can determine whether patients with lower urinary tract symptoms have hematuria, proteinuria, pusuria and urine sugar.
4.Serum PSA
Prostate cancer, BPH, and prostatitis may all elevate serum PSA. Therefore, serum PSA is not unique to prostate cancer. In addition, urinary tract infection, prostate puncture, acute urinary retention, indwelling catheterization, rectal examinations and prostate massage can also affect the serum PSA value.
Serum PSA is closely related to age and race. Serum PSA generally increases after the age of 40 years, and PSA levels vary among different ethnic groups. Serum PSA values correlate with prostate volume, but serum PSA correlates with BPH at 0.30 ng/ml and with prostate cancer at 3.5 ng/ml. Serum PSA can be used as an indication for puncture biopsy of prostate cancer. PSA ≥4ng/ml is generally used clinically as a cut-off point. Serum PSA as a risk factor can predict the clinical progression of BPH and thus guide the choice of treatment.
5.Ultrasound examination
Ultrasonography can provide insight into prostate morphology, size, presence of abnormal echogenicity, degree of protrusion into the bladder, and residual urine volume. Transrectal ultrasound can also accurately determine the volume of the prostate (calculated as 0.52 x anterior and posterior diameter x left and right diameter x upper and lower diameter). In addition, transabdominal ultrasound can understand whether there is fluid accumulation, dilatation, stones or occupying lesions in the urinary system (kidney, ureter).
6.Urinary flow rate examination
There are two main indicators (parameters) of urine flow rate: maximum urine flow rate and average urine flow rate, of which maximum urine flow rate is more important. However, a reduced maximum urinary flow rate cannot distinguish between obstruction and reduced contractility of the detrusor muscle. It should be combined with other tests and, if necessary, urodynamic studies. The maximum flow rate is highly individual and volume-dependent, so it is more accurate when the urine volume is between 150-200 ml and can be repeated if necessary.
Treatment section
I. Watchful waiting
Watchful waiting is a non-pharmaceutical, non-surgical treatment that includes patient education, lifestyle guidance, and follow-up. Because BPH is a progressive benign proliferative process in prostate histology, its progression is difficult to predict. After a long period of follow-up, only a minority of BPH patients may develop complications such as urinary retention, renal insufficiency, and bladder stones. Therefore, watchful waiting can be an appropriate management for most patients with BPH, especially when the patient’s quality of life has not yet been significantly affected by lower urinary tract symptoms.
(i) Indications
Watchful waiting can be used in patients with mild lower urinary tract symptoms (I-PSS score ≤7) and in patients with moderate or more symptoms (I-PSS score ≥8) while quality of life has not yet been significantly affected.
Prior to receiving watchful waiting, patients should undergo a comprehensive examination (all components of the initial evaluation) to exclude various BPH-related comorbidities.
(ii) Content of watchful waiting
1. Patient education
Patients should be educated about BPH disease, including lower urinary tract symptoms and the clinical progression of BPH, especially about the effects and prognosis of watchful waiting. The results of studies have shown that the detection rate of prostate cancer in people with lower urinary tract symptoms does not differ from that of their asymptomatic counterparts.
2. Lifestyle guidance.
Appropriate restriction of water intake can alleviate the symptoms of urinary frequency, such as time limit of water at night and attending public social occasions. However, daily water intake should not be less than 1500 ml. Alcohol and coffee have diuretic and stimulating effects and can cause symptoms such as increased urine output, frequency and urgency, so the intake of alcoholic and caffeinated beverages should be appropriately limited. Instruction on bladder emptying techniques, such as repetitive urination. Mental relaxation training to take the attention away from the desire to urinate. Bladder training to encourage patients to hold urine appropriately to increase bladder capacity and interval time between voiding.
Guidance on combined medications: patients with BPH often use multiple medications in combination with other systemic diseases; these combined medications should be understood and evaluated, and if necessary, adjusted under the guidance of the physician to reduce the impact of the combined medications on the urinary system. Treatment of coexisting constipation
The short-term goal of pharmacotherapy for patients with BPH is to relieve the patient’s lower urinary tract symptoms, and the long-term goal is to slow the clinical progression of the disease and prevent the development of comorbidities. Maintaining a high quality of life for patients while reducing the side effects of drug therapy is the overall goal of drug therapy for BPH.
1.α-blockers
① Mechanism of action and urinary tract selectivity of α-blockers.
Alpha-blockers are used to relieve bladder outlet power obstruction by blocking the adrenergic receptors distributed on the smooth muscle surface of the prostate and bladder neck and relaxing the smooth muscle. In vitro experiments have demonstrated the distribution of α1 receptors in the prostate and bladder neck, but the exact distribution and action of α1 receptor subtypes have not been demonstrated in in vivo experiments. Alpha-blockers can be classified into non-selective alpha-blockers (phenazopyridine), selective alpha-1 receptor blockers (doxazosin, alfuzosin, terazosin) and highly selective alpha-1 receptor blockers (corticosteroids) according to urinary tract selectivity.
②Recommendation.
Alpha-blockers are indicated for patients with BPH with lower urinary tract symptoms. Tamsulosin, doxazosin, alfuzosin, and terazosin are recommended for the pharmacological treatment of BPH. Prazosin as well as the non-selective alpha-blocker phenazopyridine are not recommended for the treatment of BPH.
(iii) Clinical efficacy.
Symptomatic improvement can be seen 48 hours after α-blocker treatment, but assessment of symptomatic improvement using the I-PSS should be done after 4-6 weeks of drug administration. Continuous use of alpha-blockers for 1 month without significant symptomatic improvement should not be continued.
Baseline prostate volume and serum PSA levels in patients with BPH do not affect the efficacy of alpha-blockers, and alpha-blockers do not affect prostate volume or serum PSA levels.
The results summarized by the American Urological Association BPH Guidelines Development Committee using a special Bayesian technique showed that the clinical efficacy of various alpha-blockers was similar, with some differences in side effects. For example, tamsulosin caused a lower incidence of cardiovascular system side effects, but a higher incidence of retrograde ejaculation.
④α-blockers for acute urinary retention
The results of clinical studies show that patients with acute urinary retention BPH treated with alpha-blockers have a significantly higher chance of successful removal of the urinary catheter than placebo treatment.
⑤ Side effects
Common side effects include dizziness, headache, weakness, sleepiness, postural hypotension, and retrograde ejaculation. Postural hypotension is more likely to occur in elderly and hypertensive patients.
Lower urinary tract symptoms are personally experienced by BPH patients and are most valued by the patients themselves. Lower urinary tract symptoms and the resulting decrease in quality of life are the main reasons why patients seek treatment, as patients have different levels of tolerance. Therefore, lower urinary tract symptoms and the degree of decline in quality of life are an important basis for the choice of treatment measures. Patients should be fully aware of the efficacy and side effects of various treatment methods, including watchful waiting, pharmacotherapy, and surgical treatment.
1. Indications for surgical treatment
Patients with moderate/severe BPH whose lower urinary tract symptoms have significantly affected the quality of life of patients can choose surgical treatment, especially those who have poor results with medication or refuse to accept medication.
Surgical treatment is recommended when patients with BPH present with the following complications.
Recurrent urinary retention (inability to urinate after at least one extubation or two urinary retention)
Recurrent hematuria that is not treated with 5-alpha reductase inhibitors
Recurrent urinary tract infections
Bladder stones
Secondary upper urinary tract fluid (with or without renal impairment)
Patients with BPH combined with large bladder diverticula, inguinal hernia, severe hemorrhoids or prolapse, who are clinically judged to be difficult to treat without relieving lower urinary tract obstruction, should be considered for surgical treatment. Measurement of residual urine volume and maximum urinary flow rate has some reference value for the degree of lower urinary tract obstruction due to BPH, but it is not currently considered to be an indication for surgical treatment alone because of the instability of its repeated measurements, interindividual variability, and the inability to distinguish lower urinary tract obstruction from bladder contractile weakness.
The physician’s choice of treatment modality will respect the patient’s wishes. The choice of surgical modality should take into account the physician’s treatment experience, the patient’s opinion, the size of the prostate, and the patient’s concomitant disease and general condition.
2. Surgical treatment modalities
The effect of BPH treatment is mainly reflected in the change of the patient’s subjective symptoms (e.g. I-PSS score) and objective indicators (e.g. maximum urinary flow rate). The evaluation of treatment methods should take into account the treatment effect, complications and socio-economic conditions and other comprehensive factors.
(1) Conventional surgery
The standard surgical treatment methods are transurethral resection of the prostate (TURP), transurethral resection of the prostate (TUIP) and open prostate removal. TURP is still the best way to treat BPH. Various surgical approaches have treatment outcomes close to or similar to TURP, but differ in their scope of application and complications. As an alternative to TURP or TUIP, transurethral electrical vaporization of the prostate (TUVP) or plasma bipolar electrosurgery (PKVP) is now also used for surgical treatment. All of the above treatments are able to improve more than 70% of the lower urinary tract symptoms in patients with BPH.
① TURP
It is mainly used to treat BPH patients with prostate volume below 80 ml, and the limit of prostate volume is relaxed appropriately according to the technical proficiency of the surgeon. The incidence of blood volume expansion and dilutional hyponatremia (transurethral electrodesiccation syndrome) due to excessive absorption of flushing fluid is about 2%. Risk factors for transurethral resection syndrome include high intraoperative bleeding, long operative time, and large prostate volume. the risk of transurethral resection syndrome increases significantly with longer TURP procedures. The chance of needing blood transfusion is about 2-5%. The incidence of various post-operative comorbidities: urinary incontinence 1-2.2%, retrograde ejaculation 65-70%, bladder neck contracture about 4%, urethral stricture about 3.8%.
② TUIP
It is indicated for patients with prostate volume less than 30 ml and without middle lobe hyperplasia. the degree of improvement of patients’ lower urinary tract symptoms after TUIP treatment is similar to that of TURP. Compared to TURP, there are fewer complications, a lower risk of bleeding and need for blood transfusion, a lower incidence of retrograde ejaculation, and a shorter operative time and hospital stay. However, the long-term recurrence rate is higher than that of TURP.
③Open prostatectomy
It is mainly suitable for patients with prostate volume greater than 80ml, especially those who need to operate together with bladder stones or bladder diverticulum. The common procedures are suprapubic prostatectomy and retropubic prostatectomy. The incidence of postoperative comorbidities is higher than that of TURP: about 1% for urinary incontinence, 80% for retrograde ejaculation, 1.8% for bladder neck contracture, and 2.6% for urethral stricture.
④TUVP
For patients with BPH who have poor coagulation and a small prostate volume. It is an alternative to TUIP or TURP. The long-term complications are similar to those of TURP.
⑤ PKVP
Transurethral resection of the prostate is performed in a similar manner to monopolar electrodes using a bipolar plasma electrodesection system. The incidence of intraoperative bleeding and transurethral electrodesiccation syndrome is reduced due to the use of saline as the intraoperative irrigation fluid.
3. Combined drug therapy
Combination drug therapy refers to the combined application of alpha-blockers and 5-alpha reductase inhibitors for the treatment of BPH.
(1) Recommendation
Combination drug therapy is suitable for BPH patients with enlarged prostate volume and lower urinary tract symptoms. patients at greater risk of clinical progression of BPH are more suitable for combination therapy. The risk of clinical progression of BPH in a specific patient, the patient’s wishes, economic status, and the increase in costs associated with combination therapy should be fully considered before using combination therapy.
(2) Clinical efficacy
The results of the current study confirm the long-term clinical efficacy of combination therapy. The study results showed that both doxazosin and finasteride significantly reduced the risk of clinical progression of BPH compared to placebo; and the combination of doxazosin and finasteride further reduced the risk of clinical progression of BPH. Since the mean prostate volume of the patients involved in the study was 31 ml, with 69% of patients with prostate volume less than 40 ml, further analysis of the treatment effect and risk of clinical progression in patients with different prostate volumes could help in the treatment selection of BPH.
2. 5-alpha reductase inhibitors
5-Alpha reductase inhibitors inhibit the conversion of testosterone to dihydrotestosterone in the body, thereby reducing the amount of dihydrotestosterone in the prostate gland and achieving the therapeutic goal of reducing prostate volume and improving urinary difficulties. The 5-alpha reductase inhibitors currently used in China include Finasteride and Epristeride.
(1)Evaluation
Finasteride is indicated for the treatment of patients with BPH who have enlarged prostate volume with lower urinary tract symptoms, and is not indicated for patients who have only lower urinary tract symptoms without enlarged prostate volume.
Finasteride may be used to prevent clinical progression of BPH in patients who are at high risk for clinical progression of BPH, such as developing urinary retention or undergoing surgical treatment. Patients should be informed of the risk of clinical progression of BPH if they do not receive treatment, and the side effects and longer duration of treatment associated with finasteride therapy should be fully considered.
(2) Clinical efficacy.
Studies have shown that finasteride is more effective in treating patients with larger prostate volumes (≥40 ml) and/or higher serum PSA levels (PSA ≥1.4 ng/ml). The long-term efficacy of finasteride has been demonstrated, with results from randomized controlled trials showing maximum efficacy after 6 months of finasteride use. The efficacy of continuous drug treatment for 6 years remains stable.
Several studies have shown that finasteride reduces the incidence of hematuria in patients with BPH. Data from studies have shown that preoperative application of finasteride (5 mg/day for more than 4 weeks) before transurethral resection of the prostate (TURP) reduces intraoperative bleeding during TURP in BPH patients with large prostate volume.
(3) Side effects.
The most common side effects of finasteride include erectile dysfunction, abnormal ejaculation, low libido and others such as gynecomastia feminization and mastalgia.
(4) Finasteride affects serum PSA levels.
Finasteride can reduce serum PSA levels. Taking finasteride 5mg daily for 1 year can reduce PSA levels by 50%. Doubling the serum PSA level in patients on finasteride does not affect its efficacy in detecting prostate cancer.
Minimally invasive treatment
1.Transurethral microwave thermotherapy (TUMT)
The principles of various microwave therapies are similar. Over 45℃ is high energy therapy. TUMT thermotherapy can partially improve the urinary flow rate and lower urinary tract symptoms in BPH patients.
2. Transurethral needle ablation (TUNA)
TUNA is a simple and safe treatment method. It is indicated for high-risk patients who cannot undergo surgical procedures.
It is not recommended as the first-line treatment for general patients. Postoperative improvement in lower urinary tract symptoms is about 50-60%, with an average increase in Qmax of about 40-70%, and the need to undergo TURP at 3 years is about 20%. Long-term efficacy needs to be further observed.
3.Prostate stenting
A prostate stent is a metal (or polyurethane) device placed endoscopically in the urethra of the prostate. It can relieve lower urinary tract symptoms due to BPH. It is only indicated for high-risk patients with indications for surgical treatment and can be used as an alternative treatment to catheterization. Common complications include stent displacement, calcium deposition, stent occlusion, infection, chronic pain, etc.
4.Other therapies
The long-term efficacy of chemical ablation therapy such as high energy focused ultrasound (HIFU), transurethral balloon expansion of the prostate, and prostate alcohol injection is uncertain among the treatment options for BPH, and there is no clear evidence to support these techniques as a treatment option for BPH.
Laser Therapy
Modalities with proven efficacy in prostate laser treatment include transurethral holmium laser prostate enucleation, transurethral laser vaporization of the prostate, and transurethral laser coagulation of the prostate. The purpose of relieving obstruction is achieved through tissue vaporization or delayed tissue loss after coagulative necrosis of tissue.
(1) Transurethral holmium laser prostate enucleation (HoLR)
The peak energy produced by the Ho:YAG laser leads to vaporization of tissue and precise and effective removal of prostate tissue.The duration of indwelling catheterization after HoLRP is short. Postoperative dyspareunia is the most common complication with an incidence of about 10% and retrograde ejaculation in 75-80% of patients.
(2) Transurethral laser vaporization of the prostate (VLAP)
Similar to electrovaporization of the prostate, laser energy is used to vaporize the prostate tissue for the purpose of surgical treatment. Short-term improvements in IPSS scores, urinary flow rate, and quality of life index are comparable to TURP. The incidence of postoperative urinary retention requiring catheterization is higher than for TURP. there is no pathological tissue after surgery. Long-term efficacy awaits further study.
(3) Transurethral interstitial laser coagulation (ILC)
The distance between the fiber tip and the prostate tissue is kept about 2 mm. The energy density is sufficient to coagulate the tissue, but not to vaporize it. The coagulated tissue will eventually necrotize and fall off, thus reducing obstruction. Advantages include its simplicity, risk of bleeding, and low water absorption rate. The incidence of urinary retention requiring catheterization after surgery is 21%, which is significantly higher than that of TURP (5%); the incidence of postoperative urinary tract irritation (66%) is also significantly higher than that of TURP (15%), and the reasons for this need to be further investigated.