Lower urinary tract symptoms of prostate enlargement are personally experienced by patients with BPH 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, the degree of lower urinary tract symptoms and quality of life decline is an important basis for the selection of treatment measures. In order to fully understand the patient’s wishes, the efficacy and side effects of various treatment methods, including watchful waiting, pharmacological treatment, and surgical treatment, are explained to the patient.
I. Watchful waiting
Watchful waiting is a non-drug, non-surgical treatment measure that includes patient education, lifestyle guidance, and follow-up visits. Because BPH is a progressive benign proliferative process in prostate histology, its development is less predictable, and only a few of BPH patients may develop complications such as urinary retention, renal insufficiency, and bladder stones after a long follow-up period. 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.
1. Recommendation: 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.
2. Clinical outcome: 85% of patients on watchful waiting remain stable at 1 year of follow-up and 65% have no clinical progression at 5 years.
3. Content of watchful waiting: ① Patient education: Patients undergoing watchful waiting should be provided with knowledge about BPH disease, including lower urinary tract symptoms and clinical progression of BPH, and in particular, patients should be informed about the effects and prognosis of watchful waiting. Patients with BPH are usually more concerned about the risk of prostate cancer, and 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 peers. ②Lifestyle guidance: Appropriate water restriction can alleviate urinary frequency symptoms, such as time limits on 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. ③ Guidance on combined medications: patients with BPH often use multiple medications at the same time due to the combination of other systemic diseases. Patients should be informed and evaluated for these combined medications and adjusted under the guidance of other specialists if necessary to reduce the impact of combined medications on the urinary system. Treatment of coexisting constipation.
4. Follow-up: Follow-up is an important clinical process for patients undergoing watchful waiting for BPH. The first follow-up visit will be conducted in the sixth month after the start of watchful waiting, and then once a year thereafter. The purpose of the follow-up visit is to understand the patient’s progress, whether there is clinical progression and BPH-related comorbidities and/or absolute surgical indications, and to switch to pharmacological or surgical treatment according to the patient’s wishes. The follow-up visit will consist of the components of the initial evaluation.
II. Pharmacological treatment
The short-term goal of pharmacological treatment for patients with BPH is to relieve the patient’s lower urinary tract symptoms, and the long-term goal is to delay the clinical progression of the disease and prevent the development of comorbidities. Maintaining a high quality of life while reducing the side effects of drug therapy is the overall goal of drug therapy for BPH.
(i) Alpha-blockers
1.The principle of action of alpha-blockers: It is by blocking the adrenergic receptors distributed on the smooth muscle surface of the prostate and bladder neck, relaxing the smooth muscle and achieving the effect of relieving bladder outlet power obstruction.
2. Recommendation: alpha-blockers are indicated for patients with BPH who have lower urinary tract symptoms. Tamsulosin, doxazosin, alfuzosin and terazosin are recommended for the pharmacological treatment of BPH. Nabepidil can be selected for the treatment of BPH. Prazosin as well as the non-selective receptor blocker phenazopyridine are not recommended for the treatment of BPH.
3, clinical efficacy: various α1-blockers can significantly improve the patient’s symptoms, resulting in an average improvement of 30-40% in symptom scores and 16-25% in maximum urinary flow rate. Phenobarbital, which was initially used, had significant side effects and was therefore difficult for patients to accept. α-blocker treatment resulted in symptom improvement within 48 hours, but assessment of symptom improvement using the I-PSS should be performed after 4-6 weeks of drug use. Continuous use of alpha-blockers for 1 month without significant symptomatic improvement should not be continued. The results of a clinical study of tamsulosin for BPH for up to 6 years showed that long-term use of alpha-blockers maintained a stable efficacy. The long-term efficacy of alpha-blockers alone has also been demonstrated.
4. α-blockers for acute urinary retention: The results of clinical studies have shown that patients with BPH with acute urinary retention are likely to have their urinary catheters successfully removed after treatment with α-blockers.
5. Side effects : Common side effects include dizziness, headache, weakness, sleepiness, postural hypotension, retrograde ejaculation, etc. Postural hypotension is more likely to occur in elderly and hypertensive patients.
(II) 5-alpha reductase inhibitors
1. Mechanism of action: 5-alpha reductase inhibitors inhibit the transformation of testosterone to dihydrotestosterone in the body, thereby reducing the content 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 erestrogen.
2. Recommendation: Finasteride is indicated for the treatment of BPH patients with increased prostate volume with lower urinary tract symptoms. For patients at high risk for clinical progression of BPHI, finasteride may be used to prevent clinical progression of BPH, such as developing urinary retention or undergoing surgical treatment. Patients should be informed of the risk of clinical progression of BPHI if they do not receive treatment, and the side effects and longer duration of finasteride treatment should be fully considered.
Clinical efficacy: The results of several large-scale randomized clinical trials have confirmed the effectiveness of finasteride, reducing prostate volume by 20-30%, improving patients’ symptom scores by about 15%, increasing urinary flow rates by about 1,3-1,6 ml/s, and reducing the risk of acute urinary retention and the need for surgical intervention by about 50% in patients with BPH. Studies have shown that finasteride is more effective in patients with larger prostate volumes and/or higher serum PSA levels. 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 has remained stable. Several studies have shown that finasteride reduces the incidence of hematuria in patients with BPH. Data from studies have shown that finasteride (5 mg/day for more than 4 weeks) applied before transurethral resection of the prostate can reduce intraoperative bleeding in patients with BPH with large prostate volume.
4. Side effects: The most common side effects of finasteride include erectile dysfunction, abnormal ejaculation, low libido and others such as gynecomastia and mastalgia.
5. Finasteride affects serum PSA level: Finasteride can reduce the serum PSA level, taking Finasteride 5mg per day for 1 year can reduce the PSA level by 50%. For patients who applied finasteride, doubling their serum PSA level did not affect its efficacy in detecting prostate cancer.
6.Elestromide: Elestromide can reduce I-PSS score, increase urinary flow rate, reduce prostate volume and decrease residual urine volume.
(iii) Combination therapy
The combination therapy refers to the combined application of alpha-blockers and 5-alpha reductase inhibitors for the treatment of BPH.1 Recommendation: Combination therapy is suitable for patients with BPH who have increased prostate volume and lower urinary tract symptoms.2 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 current study results confirm the long-term clinical efficacy of combination therapy. Both doxazosin and finasteride significantly reduced the risk of clinical progression of BPH; and the combination of doxazosin and finasteride further reduced the risk of clinical progression of BPH. Further analysis of the results revealed that when the prostate volume was greater than or equal to 25 ml, the combination therapy reduced the risk of BPH progression better than doxazosin or finasteride monotherapy.
(iv) Traditional Chinese medicine and botanical preparations
Chinese medicine has made an indelible contribution to the development of medicine and health in China as well as the health of the Chinese nation. At present, there are many kinds of traditional Chinese medicine applied in the clinical treatment of BPH, and botanical preparations, such as Pulsatilla, have obtained certain clinical efficacy in alleviating the symptoms of lower urinary tract associated with BPH, and have achieved wider clinical application at home and abroad. Since the composition of herbal and botanical preparations is complex and the specific biological mechanisms of action have not been elucidated, active basic research on various drugs including herbal medicines is beneficial to further consolidate the international status of herbal and botanical preparations. Meanwhile, large-scale randomized controlled clinical studies based on the principles of evidence-based medicine are of positive significance to further promote the clinical application of herbal and botanical preparations in the treatment of BPH.
III. Surgical treatment
I. Purpose of surgical treatment: BPH is a progressive disease, and some patients eventually need surgical treatment to relieve lower urinary tract symptoms and their impact on quality of life and complications.
II. Indications for surgical treatment: Patients with severe BPH or those whose lower urinary tract symptoms have significantly affected their quality of life may choose surgical treatment, especially when medication is not effective or when patients refuse to accept medication. Surgical treatment is recommended when BPH leads to the following complications: recurrent urinary retention (inability to urinate after at least one extubation or two); recurrent hematuria, ineffective with 5α-reductase inhibitors; recurrent urinary tract infections; bladder stones; secondary upper urinary tract hydrocele (with or without renal impairment.) Patients with BPH combined with a large bladder diverticulum, inguinal hernia, severe hemorrhoids or prolapse are judged clinically Surgical treatment should be considered for those who have difficulty achieving a therapeutic outcome without relieving lower urinary tract obstruction. The measurement of residual urine volume has some reference value for the degree of lower urinary tract obstruction due to BPH, but because of the instability of repeated measurements, interindividual variability, and the inability to distinguish lower urinary tract obstruction from bladder contractile weakness, it is not considered possible to determine the upper limit of residual urine volume that can be used as a surgical guideline. However, surgical treatment should be considered in patients with BPH who have significantly increased residual urine to the point of overflow incontinence. The choice of treatment by the urologist should respect the patient’s wishes. The choice of surgical treatment should take into account the surgeon’s personal experience, the patient’s opinion, the size of the prostate, and the patient’s concomitant disease and general condition.
The effect of BPH treatment is mainly reflected in the change of patient’s subjective symptoms (such as I-PSS score) and objective indicators (such as maximum urinary flow rate). The evaluation of treatment methods should then consider a combination of factors such as treatment effects, complications, and socioeconomic conditions.
(i) General surgery: The classical surgical methods are transurethral resection of the prostate (TURP), transurethral resection of the prostate (TUIP), and open prostate removal. TURP is still the “gold standard” of treatment for BPH. Various surgical approaches are close to or similar to TURP, but the scope of application and complications vary. As an alternative to TURP or TUIP, transurethral vaporization of the prostate (TUVP) and transurethral bipolar resection of the prostate (PKRP) are now also used in 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 applied to treat BPH patients with prostate volume below 80 ml, and the limit of prostate volume can be relaxed appropriately by skilled operators. The incidence of blood volume expansion and dilutional hyponatremia due to excessive absorption of flushing fluid is about 2%. risk factors include high intraoperative bleeding, long operative time and large prostate volume. the risk of transurethral resection syndrome increases significantly with prolonged TURP operation time. The chance of needing blood transfusion is about 2-5%. The incidence of various postoperative complications: urinary incontinence about 1-2, 2%, retrograde ejaculation about 65-70%, bladder neck contracture about 4%. Urethral stricture is about 3 or 8%.
2.TUIP: It is suitable for patients with prostate volume less than 30ml and without mesolimbic hyperplasia. the improvement of lower urinary tract symptoms in patients after TUIP treatment is similar to that of TURP. Compared to TURP, there are fewer complications, lower risk of bleeding and need for blood transfusion, lower incidence of retrograde ejaculation, shorter operative time and hospital stay. However, the long-term recurrence rate is higher than that of TURP.
3, open prostate removal: mainly for patients with prostate volume greater than 80ml, especially combined with bladder stones, or combined with bladder diverticulum need to be operated together. The common procedures are suprapubic prostatectomy and retropubic prostatectomy. The incidence of postoperative complications is higher than that of TURP: urinary incontinence in about 1%, retrograde ejaculation in about 80%, bladder neck contracture in about 1.8%, and urethral stricture in about 2.6%. The effect on erectile function may not be related to the surgery.
4.TUVP: It is suitable for BPH patients with poor coagulation function and small prostate volume. It is an alternative to TUIP or TURP and has a better hemostatic effect compared to TURP. The long-term complications are similar to those of TURP.
5. TUPKP: It is a transurethral resection of the prostate using a plasma bipolar electrosurgical system and performed in a similar manner to the monopolar TURP. Saline is used as the intraoperative irrigation fluid. Intraoperative bleeding and the occurrence of TURS are reduced.
(ii) Laser therapy : Laser therapy of the prostate is used to achieve relief of obstruction by tissue vaporization or delayed tissue loss after coagulative necrosis of the tissue. The most effective ways are transurethral holmium laser prostate enucleation, transurethral laser vaporization of the prostate, transurethral laser coagulation of the prostate, etc.
The peak energy produced by the Ho:YAG laser can lead to vaporization of the tissue and precise and effective removal of the prostate tissue. Postoperative dyspareunia is the most common complication with an incidence of about 10%. retrograde ejaculation occurs in 75-80% of patients, and no postoperative erectile dysfunction has been reported.
2. Transurethral laser vaporization: Similar to electrovaporization of the prostate, laser energy is used to vaporize the prostate tissue for the purpose of surgical treatment. The improvement in short-term IPSS score, urinary flow rate, and QOL index is comparable to TURP. The incidence of postoperative urinary retention requiring catheterization was higher than that of TURP. there was no postoperative pathological tissue. Long-term efficacy awaits further study.
3. Transurethral laser coagulation: It is an effective surgical method for the treatment of BPH. The distance between the tip of the fiber optic and the prostate tissue is kept about 2mm. 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 the obstruction. The advantages are its simplicity, risk of bleeding and low water absorption. The incidence of urinary retention and urinary tract irritation requiring catheterization after transurethral laser coagulation of the prostate was found to be 21% and 66%, respectively, significantly higher than the 5% and 15% rates for TURP.
(iii) Other treatments.
1, transurethral microwave thermotherapy: can partially solve the urinary flow rate and LUTS symptoms in patients with BPH. It is suitable for patients who are ineffective in medication (or unwilling to take long-term medication) and unwilling to undergo surgery, as well as high-risk patients with recurrent urinary retention who cannot undergo surgery. The principles of various microwave therapies are similar. Above 45°C is hyperthermia. Low-temperature therapy is ineffective and not recommended. Its 5-year re-treatment rate is as high as 84,4%; among them, the drug re-treatment rate reaches 46,7% and the surgical re-treatment rate is 37,7%.
2.Transurethral needle ablation: It is a simple and safe treatment method. It is suitable for high-risk patients who cannot receive surgical procedures, and is not recommended as the first-line treatment for general patients. After the operation, the lower urinary tract symptoms improve about 50-60%, the maximum urinary flow rate increases about 40-70% on average, and the need to receive TURP about 20% at 3 years. Long-term efficacy needs to be further observed.
3, prostate stent: is a metal (or polyurethane) device placed in the urethra of the prostate through the endoscope. It can relieve the lower urinary tract symptoms caused by BPH. It is only suitable for high-risk patients with recurrent urinary retention who cannot undergo surgical procedures, as an alternative treatment to catheterization. Common complications include stent migration and calcification, stent occlusion, infection, and chronic pain.
There is no clear evidence to support the use of high-energy focused ultrasound, chemical ablation therapy with prostate alcohol injection as an effective option for the treatment of BPH.