Benign prostatic hyperplasia (BPH) is the most common benign disease that causes urination disorders in middle-aged and elderly men. The main manifestations are the histological proliferation of interstitial and glandular components of the prostate, anatomical enlargement of the prostate, lower urinary tract symptoms (LUTS)-based clinical symptoms, and urodynamic bladder outlet obstruction (BOO).
Histologically, the incidence of BPH increases with age. It usually occurs after the age of 40, and is greater than 50% at the age of 60, and as high as 83% at the age of 80. Similar to histological manifestations, symptoms such as dysuria increase with age. Approximately 50% of men with a histological diagnosis of BPH have moderate to severe lower urinary tract symptoms. Studies have shown that Asians are more likely to develop moderate to severe BPH-related symptoms than Americans.
The occurrence of BPH must have two important conditions for aging and a functional testis. Domestic scholars investigated 26 elderly eunuchs in the Qing Dynasty, and found that 21 people’s prostates were completely out of reach, or significantly atrophy. However, the specific mechanism of BPH is not yet clear. It may be caused by the balance of epithelial and mesenchymal cell proliferation and apoptosis. Related factors include androgens and their interactions with estrogen, prostatic mesenchymal-glandular epithelial cell interactions, growth factors, inflammatory cells, neurotransmitters and genetic factors.
Prostatic hyperplasia causes the posterior urethra to be lengthened, compressed and deformed and narrowed, and urethral resistance increases, resulting in a series of changes in bladder function and upper urinary tract. Due to the increase in bladder pressure, compensatory hypertrophy of the detrusor muscle, instability of the detrusor muscle, and decreased compliance of the bladder occur; if the obstruction is not resolved for a long time, the detrusor muscle will lose its ability to compensate. Thickening of the bladder detrusor can lengthen and stiffen the wall of the ureter and bladder, leading to mechanical obstruction of the ureter; after the bladder is decompensated, the wall of the ureter and bladder can be shortened, and the intravesical pressure rises, resulting in ureteral reflux. Cause hydronephrosis and renal damage.
Male patients over the age of 50 with the following urinary tract symptoms should first consider the possibility of benign prostatic hyperplasia (BPH). To confirm the diagnosis, the following clinical evaluations are required.
1. Medical history inquiry
(1) Characteristics, duration and accompanying symptoms of lower urinary tract symptoms
(2) History of surgery and trauma, especially history of pelvic surgery or trauma
(3) Past history and sexually transmitted diseases, diabetes, neurological diseases
(4) Drug history, to understand whether you have taken drugs that affect the bladder outlet function currently or recently
(5) General conditions
(6) International Prostate Symptom Score (I-PSS)
The I-PSS scoring standard is currently internationally recognized as the best method for judging the severity of BPH symptoms.
I-PSS score is a subjective reflection of the severity of lower urinary tract symptoms in patients with BPH, and it has no significant correlation with maximum urine flow rate, residual urine volume, and prostate volume.
The classification of patients with I-PSS score is as follows: (total score 0-35 points)
Mild symptoms 0-7 points
Moderate symptoms 8-19 points
Severe symptoms 20-35 points
(7) Quality of life score (QOL)
QOL score (0-6 points) is to understand the subjective feelings of patients with their current level of lower urinary tract symptoms along with their lifetime. It is mainly concerned with the extent to which BPH patients are troubled by lower urinary tract symptoms and whether they can tolerate it, so it is also called trouble 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 doctors and patients and enable doctors to understand the disease state well.
2. Physical examination
(1) Digital rectal examination
It is very important to perform digital rectal examination for patients with lower urinary tract symptoms, and it should be done after the bladder is empty.
Can know if there is prostate cancer:
Clinical studies by foreign scholars have confirmed that 26-34% of patients with suspected abnormalities in digital rectal examination are finally diagnosed with prostate cancer. And the positive rate is increasing with age.
You can understand the size, shape, texture, presence or absence of nodules and tenderness of the prostate, whether the central groove becomes shallow or disappear, and the tension of the anal sphincter. Digital rectal examination is not accurate enough to judge the volume of the prostate. At present, transabdominal ultrasound or transrectal ultrasound can more accurately describe the shape and volume of the prostate.
(2) Local nervous system examination (including movement and sensation).
3. Urine routine
Urine routine can determine whether patients with lower urinary tract symptoms have hematuria, proteinuria, pyuria and urine sugar.
4. Serum PSA
Prostate cancer, BPH, and prostatitis may all increase serum PSA. Therefore, serum PSA is not unique to prostate cancer. In addition, urinary tract infection, prostate puncture, acute urinary retention, indwelling catheterization, digital rectal examination and prostate massage can also affect the serum PSA value.
Serum PSA is closely related to age and race. Generally, serum PSA will rise after the age of 40, and the PSA levels of people of different races are not the same. Serum PSA value is related to prostate volume, but the correlation between serum PSA and BPH is 0.30ng/ml, and that of prostate cancer is 3.5ng/ml. Serum PSA can be used as an indication for prostate cancer biopsy. Generally, PSA≥4ng/ml is regarded as the demarcation point in clinical practice. Serum PSA as a risk factor can predict the clinical progression of BPH, thereby guiding the choice of treatment.
5. Ultrasound examination
Ultrasound examination can understand the shape and size of the prostate, whether there is abnormal echo, the degree of penetration into the bladder, and the amount of residual urine. Transrectal ultrasound can also accurately determine the volume of the prostate (the calculation formula is 0.52 × anteroposterior diameter × left and right diameter × upper and lower diameter). In addition, transabdominal ultrasonography can understand whether the urinary system (kidney, ureter) has water, dilatation, stones or space-occupying lesions.
6. Urine flow rate check
Urine flow rate has two main indicators (parameters): maximum urine flow rate and average urine flow rate, of which the maximum urine flow rate is more important. However, a decrease in the maximum urine flow rate cannot distinguish between obstruction and decreased detrusor contractility. It also needs to be combined with other tests, and urodynamic tests are performed when necessary. The maximum urine flow rate has great individual differences and volume dependence, so it is more accurate to check when the urine volume is 150-200ml, and the check can be repeated if necessary.
1. Watchful waiting
Watchful waiting is a non-drug, non-surgical treatment measure, including patient education, lifestyle guidance, and follow-up. Because BPH is a progressive benign proliferative process in prostate histology, its development process is difficult to predict. After a long follow-up, only a small number of BPH patients may have complications such as urinary retention, renal insufficiency, and bladder stones. Therefore, for most patients with BPH, watchful waiting can be an appropriate treatment, especially when the quality of life of the patient has not been significantly affected by lower urinary tract symptoms.
Patients with mild lower urinary tract symptoms (I-PSS score ≤7) and patients with moderate or above symptoms (I-PSS score ≥8) and whose quality of life has not been significantly affected can use watchful waiting.
Before receiving watchful waiting, the patient should undergo a comprehensive examination (the contents of the initial evaluation) to exclude various BPH-related complications.
(2) The content of watch and wait
1. Patient education
Should understand the relevant knowledge of BPH disease, including lower urinary tract symptoms and clinical progress of BPH, especially should understand the effect and prognosis of watchful waiting. It should also provide relevant knowledge about prostate cancer. BPH patients usually pay more attention to the risk of prostate cancer. Research results show that the detection rate of prostate cancer in people with lower urinary tract symptoms is no different from that in asymptomatic people of the same age.
2. Lifestyle guidance:
Appropriate restriction of drinking water can relieve symptoms of frequent urination, such as limiting water at night and when attending public social occasions. But the daily water intake should not be less than 1500 ml. Alcohol and coffee have diuretic and stimulating effects, which can cause symptoms such as increased urine output, frequent urination, and urgency. Therefore, the intake of alcohol and caffeinated beverages should be appropriately restricted. Guide techniques for emptying the bladder, such as repeated urination. Mental relaxation training diverts attention from the desire to urinate. Bladder training encourages patients to hold their urine appropriately to increase bladder capacity and urination interval time.
Guidance on combined medication. BPH patients often use multiple drugs at the same time because of other systemic diseases. The situation of these combined drugs should be understood and evaluated, and adjustments should be made under the guidance of the physician if necessary to reduce the impact of combined drugs on the urinary system. Treat concurrent constipation
The short-term goal of drug therapy for patients with BPH is to alleviate the patients' lower urinary tract symptoms, and the long-term goal is to delay the clinical progression of the disease and prevent the occurrence of complications. It is the overall goal of BPH drug therapy to reduce the side effects of drug therapy while maintaining a high quality of life for patients.
① The mechanism of action and urinary tract selectivity of α-receptor blockers:
Alpha-receptor blockers block the adrenergic receptors distributed on the surface of the smooth muscle of the prostate and bladder neck, relax the smooth muscle, and achieve the effect of alleviating the dynamic obstruction of the bladder outlet. In vitro experiments have confirmed the distribution of α1 receptors in the prostate and bladder neck, but the exact distribution and role of α1 receptor subtypes have not been proven in vivo. According to the selectivity of the urinary tract, α-receptor blockers can be divided into non-selective α-receptor blockers (phenoxybenzamine), selective α1 receptor blockers (doxazosin, alfurazosin, Terazosin) and highly selective α1 receptor blocker (Koduohua).
Alpha-blockers are suitable for BPH patients with lower urinary tract symptoms. Tamsulosin, doxazosin, alfurazosin and terazosin are recommended for the drug treatment of BPH. Prazosin and the non-selective alpha-blocker phenoxybenzamine are not recommended for the treatment of BPH.
③ Clinical efficacy:
Symptoms can be improved within 48 hours after treatment with alpha-blockers, but I-PSS should be used to assess the improvement of symptoms after 4-6 weeks of medication. If there is no significant improvement in symptoms after continuous use of α-blockers for 1 month, it should not be used.
The baseline prostate volume and serum PSA level of BPH patients do not affect the efficacy of α-blockers, and α-blockers do not affect prostate volume and serum PSA levels.
The American Urological Association's BPH Diagnosis and Treatment Guidelines Development Committee used a special Bayesian technique to summarize the results and showed that the clinical efficacy of various α-receptor blockers is similar, and the side effects are somewhat different. For example, tamsulosin has a lower incidence of cardiovascular system side effects, but a higher incidence of retrograde ejaculation.
④ α-receptor blockers treat acute urinary retention
The results of clinical studies show that patients with acute urinary retention BPH have a significantly higher chance of successfully removing the catheter after receiving α-blocker treatment than placebo treatment.
⑤ Side effects
Common side effects include dizziness, headache, weakness, drowsiness, orthostatic hypotension, retrograde ejaculation, etc. Orthostatic hypotension is more likely to occur in elderly and hypertensive patients.
Lower urinary tract symptoms are the personal experience of BPH patients, and they are most important to the patients themselves. Due to the different tolerance of patients, lower urinary tract symptoms and the resulting decline in quality of life are the main reasons for patients to seek treatment. Therefore, the lower urinary tract symptoms and the degree of decline in quality of life are important basis for the choice of treatment measures. Patients should fully understand the effects and side effects of various treatment methods including watchful waiting, drug treatment, and surgical treatment.
1. Indications for surgical treatment
Patients with moderate/severe BPH whose lower urinary tract symptoms have significantly affected the patient’s quality of life may choose surgical treatment, especially those who have poor drug treatment or who refuse to receive drug treatment, may consider surgical treatment.
When the following complications occur in patients with BPH, surgery is recommended:
Repeated urinary retention (inability to urinate after at least one extubation or two urinary retention)
Repeated hematuria, 5-α reductase inhibitor treatment is ineffective
Repeated urinary tract infections
Secondary upper urinary tract hydrops (with or without renal impairment)
BPH patients with large diverticulum of the bladder, inguinal hernia, severe hemorrhoids or prolapse of the anus, if clinical judgment does not relieve the lower urinary tract obstruction, surgical treatment should be considered.
The determination of residual urine volume and maximum urine flow rate has a certain reference value for the degree of lower urinary tract obstruction caused by BPH, but due to the instability of repeated measurement, individual differences, and the inability to distinguish lower urinary tract obstruction and bladder contraction weakness At present, it is considered that it cannot be used as an indication for surgical treatment alone.
What kind of treatment the doctor chooses will respect the wishes of the patient. The choice of surgical method should take into account the doctor's treatment experience, the patient's opinion, the size of the prostate, and the patient's concomitant diseases and general condition.
2. Surgical treatment
The effect of BPH treatment is mainly reflected in the changes in patients' subjective symptoms (such as I-PSS score) and objective indicators (such as maximum urine flow rate). The evaluation of treatment methods should consider comprehensive factors such as treatment effect, complications, and socioeconomic conditions.
(1) Routine surgery
The standard surgical treatments include transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), and open prostatectomy. TURP is still the best way to treat BPH. The therapeutic effects of various surgical methods are close to or similar to TURP, but the scope of application and complications are different. As an alternative treatment to TURP or TUIP, transurethral electrovaporization of the prostate (TUVP) or plasma bipolar resection (PKVP) is currently also used in surgical treatment. All the above-mentioned various treatments can improve more than 70% of lower urinary tract symptoms in patients with BPH.
It is mainly suitable for the treatment of BPH patients whose prostate volume is below 80ml. The restriction on prostate volume is appropriately relaxed according to the doctor's technical proficiency. The incidence of blood volume expansion and dilutional hyponatremia (transurethral resection syndrome) caused by excessive absorption of washing fluid is about 2%. The risk factors of transurethral resection syndrome include excessive intraoperative bleeding, long operation time and large prostate volume. TURP operation time is prolonged, and the risk of transurethral resection syndrome is significantly increased. The chance of needing a blood transfusion is about 2-5%. The incidence of various complications after surgery: urinary incontinence 1-2.2%, retrograde ejaculation 65-70%, bladder neck contracture about 4%, urethral stricture about 3.8%.
It is suitable for patients with prostate volume less than 30ml and no mid-lobe hyperplasia. The improvement of lower urinary tract symptoms after TUIP treatment is similar to that of TURP. Compared with TURP, it has fewer complications, lower risk of bleeding and need for blood transfusion, lower incidence of retrograde ejaculation, shorter operation time and shorter hospital stay. But the long-term recurrence rate is higher than TURP.
③ Open prostatectomy
It is mainly suitable for patients with prostate volume greater than 80ml, especially those with bladder stones or bladder diverticulum that require simultaneous surgery. Commonly used surgical methods include suprapubic prostatectomy and retropubic prostatectomy. The chance of needing a blood transfusion is higher than that of TURP. The incidence of various complications after surgery: about 1% of urinary incontinence, about 80% of retrograde ejaculation, about 1.8% of bladder neck contracture, and about 2.6% of urethral stricture.
It is suitable for BPH patients with poor coagulation function and small prostate volume. It is another choice of TUIP or TURP. Long-term complications are similar to TURP.
Using a bipolar plasma resection system, transurethral resection of the prostate is performed in a similar manner to monopolar resection. Due to the use of normal saline as the intraoperative irrigation fluid, the incidence of intraoperative bleeding and transurethral resection syndrome is reduced.
3. Combined drug therapy
Combined drug therapy refers to the combined application of α-receptor blockers and 5-α reductase inhibitors to treat BPH.
Combined drug therapy is suitable for BPH patients with enlarged prostate and lower urinary tract symptoms. Patients with greater risk of clinical progression of BPH are more suitable for combination therapy. Before using combination therapy, full consideration should be given to the risk of the clinical progress of specific patients with BPH, the patient's willingness, economic status, and the cost increase brought by the combination therapy.
(2) Clinical efficacy
The current research results confirm the long-term clinical efficacy of the combination therapy. The results of the study showed that compared with placebo, both doxazosin and finasteride significantly reduced the risk of clinical progression of BPH; and the combination therapy of doxazosin and finasteride further reduced the risk of clinical progression of BPH. Since the average prostate volume of the patients involved in the study is 31ml, 69% of whom have a prostate volume less than 40ml, further analysis of the treatment effect and the risk of clinical progression of patients with different prostate volumes will help the treatment options for BPH.
2. 5-α reductase inhibitor
The 5-α reductase inhibitor inhibits the conversion of testosterone to dihydrotestosterone in the body, thereby reducing the content of dihydrotestosterone in the prostate, achieving the therapeutic purpose of reducing the volume of the prostate and improving dysuria.
The 5-α reductase inhibitors currently used in China include finasteride (Finasteride) and elisteride (Epristeride).
Finasteride is suitable for the treatment of BPH patients with enlarged prostate volume and lower urinary tract symptoms, but not for patients with only lower urinary tract symptoms but no enlarged prostate.
For patients with high risk of clinical progression of BPH, finasteride can be used to prevent the clinical progression of BPH, such as urinary retention or surgical treatment. Patients should be informed of the risk of clinical progression of BPH if they do not receive treatment. At the same time, the side effects of finasteride treatment and the longer course of treatment should be fully considered.
(2) Clinical efficacy:
Studies have shown that finasteride is more effective for patients with larger prostate volume (≥40ml) and/or higher serum PSA levels (PSA≥1.4ng/ml). The long-term efficacy of finasteride has been confirmed, and the results of randomized controlled trials have shown that the maximum efficacy is obtained after 6 months of finasteride. The efficacy of continuous drug treatment for 6 years has been stable.
Multiple studies have shown that finasteride can reduce the incidence of hematuria in patients with BPH. Research data show that preoperative transurethral resection of the prostate (TURP) with finasteride (5 mg/day, more than 4 weeks) can reduce the amount of bleeding during TURP in patients with BPH with larger prostate volume.
(3) Side effects:
The most common side effects of finasteride include erectile dysfunction, abnormal ejaculation, low libido, and other such as feminization of male breasts and breast pain.
(4) Finasteride affects serum PSA levels:
Finasteride can reduce the serum PSA level. Taking finasteride 5mg daily for 1 year can reduce the PSA level by 50%. For patients using finasteride, doubling their serum PSA levels will not affect their performance in detecting prostate cancer.
Minimally invasive treatment
1. Transurethral microwave hyperthermia (TUMT)
The principles of various microwave therapy devices are similar. Above 45°C is high-energy therapy. It is suitable for high-risk patients who cannot accept surgery, and is not recommended as a first-line treatment for general patients. TUMT hyperthermia can partially improve the urine flow rate and lower urinary tract symptoms of BPH patients.
2. Transurethral Acupuncture (TUNA)
TUNA is a simple and safe treatment method. It is suitable for high-risk patients who cannot accept surgery.
It is not recommended as a first-line treatment for general patients. Postoperative lower urinary tract symptoms are improved by about 50-60%, Qmax increases by about 40-70% on average, and TURP is about 20% required for 3 years. The long-term efficacy needs further observation.
3. Prostate stent
The prostate stent is a metal (or polyurethane) device placed in the urethra of the prostate through an endoscope. Can relieve lower urinary tract symptoms caused by BPH. It is only suitable for high-risk patients with indications for surgical treatment, and can be used as an alternative treatment for catheterization. Common complications include stent displacement, calcium deposition, stent occlusion, infection, and chronic pain.
4. Other treatments
Among the treatment options for BPH, the long-term efficacy of chemical ablation treatments such as high-energy focused ultrasound (HIFU), transurethral prostatic balloon dilatation, and prostate alcohol injection is uncertain, and there is no clear evidence to support these techniques as treatment options for BPH.
Prostate laser treatment has definite curative effects including transurethral holmium laser enucleation of the prostate, transurethral laser vaporization of the prostate, and transurethral laser coagulation of the prostate. The obstruction is relieved by delayed tissue shedding after tissue vaporization or tissue coagulation necrosis.
(1) Transurethral Holmium Laser Enucleation of Prostate (HoLR)
The peak energy produced by the Ho:YAG laser can lead to the vaporization of tissue and the precise and effective removal of prostate tissue. The indwelling catheterization time after HoLRP is short. Difficulty urinating after surgery is the most common complication, the incidence is about 10%, and 75-80% of patients have retrograde ejaculation.
(2) Transurethral laser vaporization of the prostate (VLAP)
Similar to prostate electrovaporization, the prostate tissue is vaporized with laser energy to achieve the purpose of surgical treatment. The improvement of short-term IPSS score, urinary flow rate, and quality of life index was comparable to that of TURP. The incidence of postoperative urinary retention requiring catheterization is higher than that of TURP. There was no pathological tissue after the operation. The long-term efficacy remains to be further studied.
(3) Transurethral interstitial laser coagulation (ILC)
Keep a distance of about 2mm between the tip of the fiber and the prostate tissue. The energy density is sufficient to coagulate the tissue, but it will not vaporize the tissue. The solidified tissue will eventually die and fall off, thereby reducing the obstruction. The advantage lies in its simple operation, bleeding risk and low water absorption rate. The incidence of postoperative urinary retention requiring catheterization was 21%, which was significantly higher than that of TURP (5%); the incidence of postoperative urinary tract irritation (66%) was also significantly higher than that of TURP (15%), and the reasons for this need to be further improved the study
BPH is a progressive disease, and some patients will eventually need surgical treatment to relieve lower urinary tract symptoms and their impact on quality of life and complications.
Follow-up is an important clinical process of waiting for patients with BPH. The first follow-up visit will be carried out in the 6th month after the start of watchful waiting, and once a year thereafter. The purpose of follow-up is mainly to understand the development of the disease, whether there is clinical progress, BPH-related comorbidities and/or absolute surgical indications, and to switch to medical or surgical treatment according to wishes. The content of the follow-up is the content of the initial evaluation.