Clinical practice guidelines exist for the evaluation and treatment of patients with benign prostatic hyperplasia. Following evaluation as outlined above, patients should be offered various forms of therapy for benign prostatic hyperplasia. Patients are advised to consult with their primary care clinicians and make an educated decision on the basis of the relative efficacy and side effects of the treatment options (Table 23–4).
Table 23–4.Summary of benign prostatic hyperplasia treatment outcomes.1 ||Download (.pdf) Table 23–4. Summary of benign prostatic hyperplasia treatment outcomes.1
|Outcome ||TUIP ||Open Surgery ||TURP ||Watchful Waiting ||Alpha-Blockers ||Finasteride2 |
|Chance for improvement1 ||78–83% ||94–99.8% ||75–96% ||31–55% ||59–86% ||54–78% |
|Degree of symptom improvement (% reduction in symptom score) ||73% ||79% ||85% ||Unknown ||51% ||31% |
|Morbidity and complications1 ||2.2–33.3% ||7–42.7% ||5.2–30.7% ||1–5% ||2.9–43.3% ||8.8–13.6 |
|Death within 30–90 days1 ||0.2–1.5% ||1–4.6% ||0.5–3.3% ||0.8% ||0.8% ||0.8% |
|Total incontinence1 ||0.1–1.1% ||0.3–0.7% ||0.7–1.4% ||2% ||2% ||2% |
|Need for operative treatment for surgical complications1 ||1.3–2.7% ||0.6–14.1% ||0.7–10.1% ||0 ||0 ||0 |
|Erectile dysfunction1 ||3.9–24.5% ||4.7–39.2% ||3.3–34.8% ||3% ||3% ||2.5–5.3% |
|Retrograde ejaculation ||6–55% ||36–95% ||25–99% ||0 ||4–11% ||0 |
|Loss of work in days ||7–21 ||21–28 ||7–21 ||1 ||3.5 ||1.5 |
|Hospital stay in days ||1–3 ||5–10 ||3–5 ||0 ||0 ||0 |
Patients with mild symptoms (AUA scores 0–7) should be managed by watchful waiting only. Medical therapy is appropriate for many others. Absolute surgical indications include refractory urinary retention (failing at least one attempt at catheter removal), large bladder diverticula, or any of the following sequelae of benign prostatic hyperplasia: recurrent urinary tract infection, recurrent gross hematuria, bladder stones, or chronic kidney disease.
The risk of progression or complications is uncertain. However, in men with symptomatic disease, it is clear that progression is not inevitable and that some men undergo spontaneous improvement or resolution of their symptoms.
Retrospective studies on the natural history of benign prostatic hyperplasia are inherently subject to bias, relating in part to patient selection and also to the type and extent of follow-up. Very few prospective studies addressing the natural history have been reported. One small series demonstrated that approximately 10% of symptomatic men may progress to urinary retention while 50% of patients demonstrate marked improvement or resolution of symptoms. A large randomized study compared finasteride with placebo in men with moderate to severely symptomatic disease and enlarged prostates on DRE. Patients in the placebo arm demonstrated a 7% risk of developing urinary retention over 4 years.
Men with moderate or severe symptoms can also be observed if they so choose. The optimal interval for follow-up is not defined, nor are the specific end points for intervention.
The human prostate and bladder base contains alpha-1-adrenoceptors, which show a contractile response to agonists. Alpha-blockade has been shown to result in both objective and subjective degrees of improvement in the symptoms and signs of benign prostatic hyperplasia in some patients. Alpha-blockers can be classified according to their receptor selectivity (Table 23–5) as well as their half-life.
Table 23–5.Alpha-blockade for benign prostatic hyperplasia. ||Download (.pdf) Table 23–5. Alpha-blockade for benign prostatic hyperplasia.
|Agent ||Action ||Oral Dose |
|Prazosin ||Alpha-1-blockade ||1–5 mg twice daily |
|Terazosin ||Alpha-1-blockade ||1–10 mg daily |
|Doxazosin ||Alpha-1-blockade ||1–8 mg daily |
|Tamsulosin ||Alpha-1a-blockade ||0.4 or 0.8 mg daily |
|Alfuzosin ||Alpha-1a-blockade ||10 mg daily |
|Silodosin ||Alpha-1a-blockade ||4 or 8 mg daily |
|Tadalafil ||Phosphodiesterase type 5 inhibitor ||5 mg daily |
Prazosin is an effective short-acting, nonselective alpha-blocker; however, it requires dose titration and twice daily dosing. Typical side effects include orthostatic hypotension, dizziness, tiredness, retrograde ejaculation, rhinitis, and headache.
Long-acting, nonselective alpha-blockers allow for once-a-day dosing, but dose titration is still necessary because side effects similar to those seen with prazosin may occur. Terazosin improves symptoms and in numerous studies is superior to placebo or finasteride. Terazosin is started at a dosage of 1 mg orally daily for 3 days, increased to 2 mg orally daily for 11 days, then 5 mg orally daily. Additional dose escalation to 10 mg orally daily can be performed if necessary. Doxazosin is started at a dosage of 1 mg orally daily for 7 days, increased to 2 mg orally daily for 7 days, then 4 mg orally daily. Additional dose escalation to 8 mg orally daily can be performed if necessary.
Alpha-1a-receptors are localized to the prostate and bladder neck. Selective blockade of these receptors results in fewer systemic side effects than nonselective alpha-blocker therapy (orthostatic hypotension, dizziness, tiredness, rhinitis, and headache), thus obviating the need for dose titration. The typical dose of tamsulosin is 0.4 mg orally daily taken 30 minutes after a meal. Alfuzosin is a long-acting alpha-1a-blocker; its dose is 10 mg orally once daily with food and does not require titration. Several randomized, double-blind, placebo-controlled trials have been performed comparing terazosin, doxazosin, tamsulosin, and alfuzosin with placebo. All agents have demonstrated safety and efficacy. Floppy iris syndrome, a complication of cataract surgery, can occur in patients taking alpha-blockers and alpha-1a-blockers.
2. 5-alpha-reductase inhibitors
Finasteride and dutasteride block the conversion of testosterone to dihydrotestosterone. These medications impact the epithelial component of the prostate, resulting in reduction in size of the gland and improvement in symptoms. Six months of therapy is required for maximum effects on prostate size (20% reduction) and symptomatic improvement.
Several randomized, double-blind, placebo-controlled trials have been performed comparing finasteride with placebo. Efficacy, safety, and durability are well established. However, symptomatic improvement is seen only in men with enlarged prostates (greater than 40 mL by ultrasonographic examination). Side effects include decreased libido, decrease in volume of ejaculate, and erectile dysfunction. Serum PSA is reduced by approximately 50% in patients receiving finasteride therapy, but the % free PSA is unchanged. Therefore, in order to compare with pre-finasteride PSA levels, the serum PSA of a patient taking finasteride should be doubled.
A report suggests that finasteride therapy may decrease the incidence of urinary retention and the need for operative treatment in men with enlarged prostates and moderate to severe symptoms. The larger the prostate over 40 mL, the greater the relative-risk reduction. However, optimal identification of appropriate patients for prophylactic therapy remains to be determined. Dutasteride is a dual 5-alpha-reductase inhibitor that appears to be similar to finasteride in its effectiveness; its dose is 0.5 mg orally daily.
Both finasteride and dutasteride have been shown to be effective chemopreventive agents for prostate cancer in large, randomized clinical trials. A 25% risk reduction was observed in men with both low and high risk for prostate cancer. However, despite the strength of the evidence for 5-alpha-reductase inhibitors in reducing the risk of prostate cancer, an FDA advisory committee recommended against labeling these agents for prostate cancer chemoprevention, citing the potential increased risk of high-grade tumors in these studies (1.8% vs 1.0% for finasteride and 1% vs 0.5% for dutasteride), isolated risk reduction in low-grade tumors, and inability to apply the findings to the general population. Moreover, the FDA has included the increased risk of being diagnosed with high-grade prostate cancer in the labels of all 5-alpha-reductase inhibitors.
3. Phosphodiesterase-5 inhibitor
Tadalafil is approved by the FDA to treat the signs and symptoms of benign prostatic hyperplasia (Table 23-5); it is also approved for use in men with both urinary symptoms and erectile dysfunction. The data from two randomized, double-blind, placebo-controlled trials demonstrated significant improvements in standardized measurements of urinary function between 2 and 4 weeks after initiating treatment at 5 mg once daily, with minimal adverse effects.
The four-arm Veterans Administration Cooperative Trial compared placebo, finasteride alone, terazosin alone, and combination of finasteride and terazosin. Over 1200 patients participated, and significant decreases in symptom scores and increases in urinary flow rates were seen only in the arms containing terazosin. However, enlarged prostates were not an entry criterion; in fact, prostate size in this study was much smaller than in previous controlled trials using finasteride (32 versus 52 mL). The Medical Therapy of Prostatic Symptoms (MTOPS) trial was a large, randomized, placebo-controlled trial comparing finasteride, doxazosin, the combination of the two, and placebo in 3047 men observed for a mean of 4.5 years. Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either medication alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy. Combination therapy had the risks of additional side effects and the cost of two medications.
Phytotherapy is the use of plants or plant extracts for medicinal purposes. Several plant extracts have been popularized, including the saw palmetto berry, the bark of Pygeum africanum, the roots of Echinacea purpurea and Hypoxis rooperi, pollen extract, and the leaves of the trembling poplar. However, a prospective, randomized, double-blind, placebo-controlled trial revealed no improvement in symptoms, urinary flow rate, or quality of life for men with benign prostatic hyperplasia with saw palmetto treatment compared with placebo.
C. Conventional Surgical Therapy
1. Transurethral resection of the prostate (TURP)
Over 95% of prostate surgeries can be performed endoscopically (through the urethra). TURP is the gold standard treatment for surgical treatment of benign prostatic hyperplasia, and it often requires a 1- to 2-day hospital stay. While there are only a few head-to-head surgical studies comparing TURP to minimally invasive therapies, most studies show symptom scores and flow rate improvements are superior following TURP compared to any minimally invasive therapy. The risks of TURP include retrograde ejaculation (75%), erectile dysfunction (less than 5%), and urinary incontinence (less than 1%). Potential complications include (1) bleeding; (2) urethral stricture or bladder neck contracture; (3) perforation of the prostate capsule with extravasation; and (4) transurethral resection syndrome, a hypervolemic, hyponatremic state resulting from absorption of the hypotonic irrigating solution. This syndrome was much more prevalent when TURPs were most often performed with monopolar electrocautery but, with the increased use of bi-polar TURPs (using saline irrigation), it is now very rare. Clinical manifestations of the syndrome include nausea, vomiting, confusion, hypertension, bradycardia, and visual disturbances. The risk of transurethral resection syndrome increases with monopolar resection times over 90 minutes. Treatment includes diuresis and, in severe cases, hypertonic saline administration (see Hyponatremia, Chapter 21).
2. Transurethral incision of the prostate (TUIP)
Men with moderate to severe symptoms and small prostates often have posterior commissure hyperplasia or an “elevated bladder neck.” These patients will often benefit from incision of the prostate. The procedure is more rapid and less morbid than TURP. Outcomes in well-selected patients are comparable, though a lower rate of retrograde ejaculation has been reported (25%).
3. Simple prostatectomy (open/robotic)
When the prostate is very large, open or robotic enucleation is considered. What size is “too large” depends upon the surgeon’s experience with TURP. Glands over 100 g are usually considered for enucleation. In addition to size, other relative indications for open prostatectomy include concomitant bladder diverticulum or bladder stone and whether dorsal lithotomy positioning is or is not possible.
Simple prostatectomies can be performed with either a suprapubic or retropubic approach. Simple suprapubic prostatectomy is performed transvesically and is the operation of choice if there is concomitant bladder pathology (eg, bladder stones). These operations can also be performed via robotic-assisted laparoscopic techniques with shorter hospital stays, less blood loss, and decreased need for a suprapubic catheter.
D. Minimally Invasive Therapy
Many minimally invasive therapies are in phase 1 or 2 clinical trials; while some show promise, they have not yet received FDA approval and are not yet on the market. There has been a significant shift toward more minimally invasive therapies due to both cost of care and better data from 3- to 5-year (or more) outcomes. In addition, studies have shown decreased cost compared to medical therapies in as short as 6 months (or as long as 8 years). An overview of all the surgical options and decision making was published by the American Urological Association (Figure 23–2).
Surgical management of lower urinary tract symptoms attributed to benign prostatic hyperplasia. HoLEP, holmium laser enucleation of the prostate; PUL, prostatic urethral lift; PVP, photoselective vaporization of the prostate; ThuLEP, thulium laser enucleation of the prostate; TUIP, transurethral incision of the prostate; TUMT, transurethral microwave therapy; TURP, transurethral resection of the prostate; TUVP, transurethral vaporization of the prostate. (Reproduced, with permission, from Foster HE et al; Surgical management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA Guideline Amendment 2019. J Urol. 2019 Sep;202(3):592–8.)
Several coagulation necrosis techniques have been used.
Most urologists prefer to use visually directed laser techniques. Visual coagulative necrosis is performed under cystoscopic control, and the laser fiber is pulled through the prostate at several designated areas depending on the size and configuration of the gland. Four-quadrant and sextant approaches have been described for lateral lobes, with additional treatments directed at enlarged median lobes. Coagulative techniques do not create an immediate visual defect in the prostatic urethra—tissue is sloughed over the course of several weeks up to 3 months following the procedure.
Visual contact ablative techniques take longer in the operating room because the laser fiber is placed in direct contact with the prostate tissue, which is vaporized. Photovaporization of the prostate (PVP), an alternative laser technique, uses a high-power KTP laser. An immediate defect is obtained in the prostatic urethra, similar to that seen during TURP.
Interstitial laser therapy places laser fibers directly into the prostate, usually under cystoscopic control. Irritative voiding symptoms may be less in these patients as the urethral mucosa is spared and prostate tissue is resorbed by the body rather than sloughed.
Holmium laser enucleation of the prostate (HoLEP) is a technique of enucleating the adenomatous lobes intact and morcellating the tissue within the bladder. Advantages of HoLEP compared with other methods include ability to treat all prostate sizes, low re-treatment rates, few complications, and shorter duration of catheterization.
Advantages to laser surgery include minimal blood loss, rarity of transurethral resection syndrome, ability to treat patients during anticoagulant therapy, and outpatient surgery. Disadvantages are the lack of tissue for pathologic examination, longer postoperative catheterization time, variable effectiveness, more frequent irritative voiding complaints, and expense of laser fibers and generators.
2. Transurethral needle ablation of the prostate (TUNA)
This procedure uses a specially designed urethral catheter that is passed into the urethra. Interstitial radiofrequency needles are then deployed from the tip of the catheter, piercing the mucosa of the prostatic urethra. Radiofrequencies are then used to heat the tissue, resulting in coagulative necrosis. Subjective and objective improvement in voiding occurs. In randomized trials comparing TUNA to TURP, similar improvement was seen when comparing life scores, peak urinary flow rates, and postvoid residual urine. Bladder neck and median lobe enlargement are not well treated by TUNA.
3. Transurethral electrovaporization of the prostate
This technique uses the standard resectoscope. High current densities result in heat vaporization of tissue, creating a cavity in the prostatic urethra. The device requires slower sweeping speeds over the prostatic urethra and the depth of vaporization is approximately one-third of a standard loop. This procedure usually takes longer than a standard TURP. Long-term comparative data are needed.
Microwave hyperthermia is most commonly delivered with a transurethral catheter. Some devices cool the urethral mucosa to decrease the risk of injury. However, if temperatures do not go above 45°C, cooling is unnecessary. Symptom score and flow rate improvement are obtained, but (as with laser surgery) large randomized studies with long-term follow-up are needed to assess durability and cost-effectiveness.
5. Implant to open prostatic urethra (UroLift)
A minimally invasive, FDA-approved implant can be used to retract the enlarged lobes of the prostate in symptomatic men age 50 years and older with an enlarged prostate (less than 80 g). This implant staples the prostatic lobes to open the prostatic urethral lumen. This is done in the clinic setting with local analgesia. Short-term data show improved symptoms and voiding flows with minimal impact on erectile or ejaculatory function. Long-term comparative data are needed.
6. Water vapor thermal therapy (Rezum)
This minimally invasive, FDA-approved technique uses a transurethral device to deliver steam into the prostatic tissue and thermally destroy it. This procedure is done in the clinic or ambulatory surgery setting with 3-year data showing improvement in symptoms and voiding flows with minimal impact on erectile or ejaculatory function compared with medical therapy.