eMedicine Specialties > Urology > Benign Prostatic Hypertrophy

Interstitial Laser Coagulation of the Prostate

Author: Stanley A Brosman, MD, Clinical Professor, Department of Urology, University of California at Los Angeles Medical School
Contributor Information and Disclosures

Updated: Aug 27, 2009

Introduction

Benign prostatic hyperplasia (BPH) is the most common disorder in men older than 40 years. BPH usually starts to become symptomatic in men aged 50 years and older. Because of the intimate anatomic relationship between the bladder, urethra, and prostate, prostatic growth can alter the physiology and function of these organs and produce a symptom complex known as prostatism. Almost every man expects to have some type of prostate problem during his lifetime. Although no one knows how to prevent BPH, other than with castration or testosterone production elimination, treatment options are available that can effectively and safely ameliorate its symptoms and preserve normal bladder and kidney function.

Symptoms associated with BPH may include an increase in the frequency of urination, hesitancy in starting the urinary flow, a weaker stream, an increase in nocturia, a sensation of incomplete bladder emptying, and urgency that may be associated with incontinence. These lower urinary tract symptoms (LUTS) may result from bladder outlet obstruction (BOO)¹ or BPH. In addition, they may also be associated with an overactive bladder (OAB) in the absence of obstruction. Differentiating the pathophysiology of LUTS, BOO, and OAB allows for application of the most appropriate therapy.

LUTS may be subdivided into different categories for clinical purposes. LUTS associated with clinical BPH assumes that it is the BPH that is responsible for the symptoms, but this is not always accurate.

When symptoms become troublesome, patients seek medical attention from their primary care physician or urologist. Previously, the only therapies were open surgical procedures (eg, suprapubic prostatectomy, retropubic prostatectomy, perineal prostatectomy, transurethral resection of the prostate [TURP]). Now, various therapeutic alternatives are available, including pharmaceuticals, herbal products, or interventional procedures.

Pharmaceutical therapy consists of alpha-adrenergic blockers, 5-alpha-reductase (5aR) inhibitors, various herbal products such as saw palmetto and Pygeum africanum, and a plethora of new procedures, including microwave thermotherapy, prostate vaporization techniques, free-beam laser prostatectomies, thermotherapy with heated water, photodynamic therapy, injection therapy with alcohol, high-intensity focused ultrasound, and interstitial laser coagulation (ILC).

This article focuses primarily on one of the laser therapies, ILC of the prostate, although the other forms of intervention are discussed.

In the 1980s, several investigators began studying the application of interstitial laser energy to treat various neoplasms. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser energy was transmitted through flexible end-firing fibers inserted directly into the tumor. This produced a focal area of tissue necrosis surrounding the fiber tip. Small tumors could be effectively eradicated.

In 1991, Hofstetter suggested the use of this technique to treat BPH. Studies in animal and human prostates demonstrated the feasibility of this approach and led to clinical trials for men with symptomatic BPH. The original end-firing Nd:YAG laser fibers emitted a high-energy beam from its tip but produced only a small spherical volume of tissue destruction.

Early fibers were fragile and had a tendency to break during insertion. Recognizing the potential usefulness of this procedure, new fibers were specially designed for treating the prostate. These sturdy fibers were larger in diameter and had pointed tips to facilitate placement into prostatic tissue.

Currently, the fibers have distal-diffusing tips that radiate 360° laser-light energy along the terminal 3 mm of the fiber. During the 90-second or 3-minute laser application time (depending on which model unit is used), ellipsoid volumes of tissue coagulation are created, which surround the axis of the fiber. The affected tissue area has a diameter of 1.5-2 cm and a length of 2 cm, which corresponds to the length of the energy-diffusing fiber tip.

The laser systems, manufactured by Johnson and Johnson (Indigo), in Cincinnati, and Dornier (Fiber Tome), in Germany, are compact, readily transportable, low-power, diode laser devices that use a 15- to 20-watt variable power source. This process produces a wavelength of 800-850 nm. The current indigo system uses an 830-nm fiber, and laser energy transmits through a sterile fiber enclosed within a 2-cm long, high-temperature resistant, light-diffusing tip that fits through a cystoscope. Low-power settings minimize tissue charring, which impedes light and heat conduction and decreases the amount of tissue coagulation.

The transurethral endoscopically guided technique is preferred; however, both transperineal and transrectal approaches are used. Although transrectal ultrasonography was initially used to guide the placement of the fibers, this is rarely necessary. These laser systems (ie, transperineal, transrectal) represent an effective and safe method for relieving BPH-associated symptoms.

History of the Procedure

Although BPH is one of the most common processes in aging males, much remains to be learned about its etiology and pathophysiology. Until 10 years ago, the prevailing opinion was that the symptoms associated with BPH were due entirely to an increase in urethral resistance caused by an enlarged prostate constricting the urethra; however, since that time, obstruction has been noted to produce neurologic alterations in the bladder and prostate, which account for many of the symptoms.

The following terms describe BPH, but no uniform acceptance of any terminology exists. Regardless of which term is used, the patient seeks the attention of a urologist when symptoms of difficult urination begin.

• Prostatic enlargement
• Histologic hyperplasia
• LUTS
• BOO
• Urodynamic obstruction and other appellations

ILC is one of many minimally invasive procedures that have been introduced to alleviate the problems associated with BPH. At this time, stating that one form of therapy is distinctly advantageous over the others is not possible because few comparative studies have been performed. ILC is applicable for prostates smaller than 60 mL in volume, and this procedure, like the others, can be performed in the office with local anesthesia.

Problem

The prostate undergoes significant growth during specific periods (ie, fetal development, puberty, late middle age). At the end of puberty, the prostate size is 15-25 g, and it remains in this range until BPH develops.

Growth of BPH usually begins in men aged 30-35 years. In men aged 30-50 years, the estimated doubling time for prostate weight is 4.5 years. In men aged 50-70 years, the doubling time is 10 years. Researchers postulate that the average age-related growth rate is approximately 6 g per decade.

BPH is the most common tumor that develops in men. Symptoms are thought to develop from the interaction among the following 3 components:

• The static component results from enlargement of the inner portion, or transition zone, of the prostate. This zone is adjacent to the urethra and develops into an adenoma that compresses the peripheral zone. The transition zone is the tissue that is removed when a prostatectomy is performed, via transurethral resection, open prostatectomy, or any of the other types of procedures.
• The second, dynamic component involves the smooth muscle in the prostate, the prostatic capsule, the bladder outlet, and the proximal portion of the urethra.
• The third component is the bladder muscle (detrusor), which responds to changes related to prostate growth and tension in the smooth muscles within the prostate and proximal urethra. The bladder exhibits a decrease in contractility that leads to atony and urinary retention, an increase in uninhibited contractions that produces frequency and urgency, or a combination of both.

Enlargement of the prostatic adenoma produces changes in the detrusor that are responsible for many of the symptoms that men experience. The smooth muscles that encircle the urethra and course through the prostate are responsible for maintaining muscle tone in the urethra. The dynamic changes in these smooth muscles result in symptoms of frequency, urgency that may be accompanied by urge incontinence, nocturia, and postvoid dribbling. These LUTS tend to occur in men younger than 65 years. Often, these men have prostates that are not very enlarged and have relatively good flow rates and empty their bladders fairly well.

The static or obstructive symptoms, which usually occur in older men, include a weak stream, hesitancy, inability to complete urination suddenly without postvoid dribbling, sensation of incomplete bladder emptying, straining to urinate, and urinary retention (in some men). These symptoms are associated with an enlarged prostate.

• Category 1: Although a weak stream often is associated with BOO, other disorders (eg, urethral stricture) can produce the same symptom. Researchers define hesitancy as an increase in time from the attempt to initiate micturition and the actual start of the urinary flow. In men without a prostate condition, the start of urinary flow usually takes only a few seconds, but, in men with obstruction, it may take several minutes.
• Category 2: This category defines irritative symptoms, including frequency and urgency, which may be coupled with some incontinence and nocturia. Urination frequency depends on many factors (eg, fluid intake, diet, medications, physical activity). Voiding at intervals of less than 2 hours with voided volumes less than 250 mL arbitrarily can be defined as frequency. Urgency describes the sudden, strong desire to urinate and may be associated with incontinence.

This symptom constellation causes most patients to seek medical attention. Most men have some, or many, of these symptoms in various degrees by the age of 70 years. The severity of symptoms and their correlation with urodynamic findings provide the basis for therapeutic intervention.

Frequency

Histologic evidence in unselected autopsy specimens demonstrates that BPH occurs in more than 40% of men aged 50-60 years and in 90% of men aged 80-90 years. The majority of men older than 50 years have some symptoms attributable to BPH. Nearly 2 million office visits per year are from men seeking the evaluation and treatment of BPH. Surgeons perform more than 300,000 procedures per year on the prostate, and an estimated 900,000 men take some type of medication or herbal supplement for a prostate condition.

Approximately 25% of men aged 55 years note a decrease in the force of urine flow, and 50% of men describe this symptom by age 75 years. According to the International Prostate Symptom Score (IPSS) index, the odds of a man aged 40-50 years developing moderate-to-severe symptoms (IPSS >8) increases with age, from 1.9 for men aged 50-59 years to 3.4 for men aged 70-79 years. The chances of men developing moderate-to-severe symptoms with a prostate larger than 50 g is 3.5 times greater than for men with smaller prostates; however, epidemiologic and clinical studies demonstrate that the relationship between prostate size and symptoms is not necessarily linear.

The proportion of men with clinical prostatism at any age is approximately the same as those with pathologic evidence of BPH, even though the correlation is poor between symptoms and prostate size. The dynamic or smooth muscle component associated with the symptoms of BPH explains this discordance; thus, some men with relatively small prostates may have severe symptoms, and some men with very large prostates may have few symptoms.

Patients' symptoms affect their quality of life. Interference with at least 1 daily activity occurs in 50% of patients, and 25% of patients report interference with activity most, or all, of the time.

Epidemiologic studies fail to demonstrate racial differences in prevalence of BPH histopathology, prostate size, or clinical diagnosis.

An inheritable form of BPH may be present in 50% of men younger than 60 years who are treated for this disease. Only 9% of men older than 60 years who are treated for BPH are predicted to have a familial risk. A large prostate size and a mean volume of 82.7 mL in men with hereditary BPH, compared to 55.5 mL in men with sporadic BPH, characterize BPH.

Etiology

BPH is characterized by an increase in the number of epithelial and stromal cells in the periurethral area, or transition zone, of the prostate. Embryonic reawakening describes the presence of new epithelial gland formation. Increases in cell numbers may occur from epithelial and stromal proliferation or apoptosis impairment.

Etiology of the hyperplastic process relates to androgens, nonandrogen testicular factors, estrogen, stromal-epithelial interactions, growth factors, neurotransmitters, and other factors awaiting definition.

The two causative factors necessary for the development of BPH are aging and the presence of functional testes. The prostate is able to grow throughout adult life, and the process may be clinically evident in men as young as age 30-40 years.

The prostate consists of a network of glandular elements embedded in a fibrostromal network with a rich vascular supply. Androgens, estrogens, other growth factors, and various cytokines mediate the close interaction between these glandular and stromal cells. The growth process within the stroma perpetuates itself and exerts control on the gland growth rate and apoptotic cycle. The urine and semen also contain growth factors that may permeate the urethra and influence epithelial cell growth. Interactions between growth factors and steroid hormones may alter the balance of cell proliferation versus apoptosis.

BPH involves growth stimulatory factors with dihydrotestosterone (DHT) and other hormones modulating their effects, which are as follows:

• Epidermal growth factor
• Epidermal growth factor receptor
• Insulin growth factors 1, 3, 4
• Insulinlike growth factor (IGF) receptors and binding proteins
• Beta fibroblast growth factor
• Keratinocyte growth factor (KGF): It is produced in stromal cells, but its receptors are located on the glandular epithelial cells. Its hormonally regulated production plays a key role in stromal-epithelial interaction

The transforming growth factor beta inhibits epithelial cell proliferation, regulates extracellular matrix synthesis and degradation, and can induce apoptosis.

The role of the testis in BPH involves the production of androgen, estrogen, and nonandrogenic substances. These 2 hormones play a pivotal role in prostatic growth because the prostate is androgen-dependent and estrogen is mitogenic. The nuclear membrane-bound enzyme, 5aR, mediates the biochemical action of testosterone and is responsible for the conversion of testosterone to DHT (ie, the active agent within the cell). Patients with BPH maintain intraprostatic levels of DHT, but these levels are not elevated. DHT levels are the same in hyperplastic and healthy glands.

In adult prostates, androgen receptors are present on glandular and stromal cells, but 5aR is present only in stromal cells. Two 5aR enzymes are encoded by separate genes. Type 1 is the predominate enzyme in extraprostatic tissues, and type 2 is found largely in the prostate.

BPH also seems to have an inheritable genetic component. The hazard-function ratio between men treated surgically for BPH compared to first-degree male relatives of the controls was 4.2, indicating a very strong relationship. A segregation analysis shows that results are consistent with an autosomal dominant inheritance pattern.

Pathophysiology

Benign prostatic hypertrophy

The traditional BPH symptom complex is initiated by enlargement of the prostate, which leads to BOO and its associated symptomatology. However, prostate size, per se, does not determine the severity or the symptom complex associated with this condition. Some men with prostates larger than 75 mL have minimal difficulty voiding, have good flow rates, and empty their bladders. Some men have minimal prostatic enlargement with severe symptoms and need some type of intervention.

Lepor et al report on the results of over 400 men enrolled in the terazosin database. Their research could demonstrate no correlation between prostate size and either peak urinary flow rates or symptom scores. They conclude that treating patients just because of an enlarged prostate may not always relieve obstruction or improve symptoms.

The following mechanisms explain why BPH may produce BOO:

• Enlarged middle lobe of the prostate, which acts as a ball valve
• Static obstruction, resulting from an enlarged prostate encircling the urethra
• Dynamic obstruction related to the contractile properties of the prostatic smooth muscle
• Restrictive prostatic capsule
• Smooth detrusor muscle tension

Controlled, randomized studies that focus on reducing prostate size and relaxing prostate smooth muscle consistently demonstrate improvement in flow rates and symptoms.

Prostatism

The prostatism theory postulates that increases in urethral resistance, which usually are associated with prostatic hyperplasia in the periurethral glands of the transition zone, result in compensatory changes in detrusor function. The resulting elevated detrusor pressures that are required to maintain urinary flow when outflow resistance is increasing occur at the expense of normal bladder function.

Changes in detrusor function (caused by obstruction), combined with incremental increases in smooth muscle tension and a resistant prostatic capsule and compounded by age-related changes in the detrusor and the nervous system, produce the characteristic symptoms of frequency, urgency, nocturia, and weak urine flow associated with prostatism.

Presentation

Symptoms that characterize BPH and distinguish the need for some type of intervention of the prostate are as follows:

• Prostatism can be separated into an obstructive or irritative (dynamic) component: The typical obstructive symptom is a weak flow, which is not pathognomonic of obstruction because other entities (eg, urethral stricture) can produce the same symptom.
• Hesitancy in beginning urination: This is described as a prolonged time between patient attempt to initiate voiding and time that voiding actually begins. Normally, this interval takes only a few seconds, but it can take several minutes in men with severe obstruction whose bladder cannot generate enough pressure to overcome urethral resistance.
• Patient inability to abruptly terminate urination results in postvoid dribbling, which is caused by detrusor fatigue or urine trapped in the bulbar urethra. This particular symptom often develops in healthy men.
• Sensation of incomplete bladder emptying is frequent but does not necessarily correlate with ultrasound measurements of residual urine.
• Overflow incontinence occurs when the detrusor is unable to contract and urine begins spilling through the urethra. This usually is associated with large residual urine or urinary retention.
• Urinary retention
  • This occurs when a patient suddenly is unable to void. Retention is also defined as a bladder that consistently retains more than 150 mL after voiding, as determined with Foley catheterization or bladder scanning.
  • In some patients, total urinary retention represents the terminal event of steadily progressive urinary obstruction and detrusor decompensation. Some type of invasive procedure is necessary in most of these men, although the recovery of detrusor function is variable and depends on how long the retention has been present. Urodynamics may provide information that predicts bladder recoverability.
  • Alcohol, antidepressants, anticholinergics, tranquilizers, and antihistamines with alpha-adrenergic activity also may cause retention. This can be reversed in some men with cessation of these agents.
• Irritative symptoms (thought to develop from detrusor instability and not directly related to obstruction)
  • Frequency
  • Nocturia
  • Urgency
  • Urge incontinence
• Frequency
  • To determine whether patient frequency is physiologic or attributable to detrusor instability, evaluate voiding times and compare them with the volume of passed urine.
  • Patients taking diuretics, those with large fluid intakes, and patients with a large caffeine intake often void frequently but pass substantial amounts of urine with each voiding. Normal voiding volumes diminish with age, but most individuals can expect to pass 250-300 mL of urine with each void.
  • Abnormal frequency includes patients with a strong urge to urinate at intervals of less than 2 hours, with volumes that average less than 200 mL.
• Urgency
  • This refers to the sudden and strong need to urinate, and incontinence may accompany this symptom.
  • This is a nonspecific symptom, which may be associated with prostatism but also occurs in patients with bladder stones, neuropathic bladder disease, bladder cancer, and some types of inflammatory bladder disease.
• Nocturia occurs in many patients but must be correlated with fluid intake, sleep patterns, and medications. Nocturia occurring more than once may be abnormal in some but readily explainable in others. Nocturia is probably the single most difficult symptom to treat in men with LUTS.

Indications

Indications for treatment depend on patient symptoms and their severity, the degree to which the symptoms bother the patient, and whether changes in bladder and renal function can be documented objectively. Some men have relatively few symptoms but are extremely bothered by them and desire therapy. Others may have significant symptoms but are quite content to live with them. Still others may have minimal symptoms but serious impairment of bladder and/or renal function.

Many men with mild-to-moderate symptoms or objective findings generally may respond to alpha-blockers, 5aR inhibitors, and herbal products such as saw palmetto and Pygeum africanum. Combinations of these agents are also used. Other interventional strategies should be used if the symptoms are not ameliorated to the patient's satisfaction, which can be judged based on an improvement in their symptom scores, or upon objective findings such as a decrease in urine flow rates, an increase in the postvoid residual, or deterioration of renal function. Some men develop side effects caused by these various agents and want the problem resolved permanently and expeditiously.

Review the options and create a management strategy if the patient's symptoms correlate with the objective data gathered from an evaluation of the urinary tract and the patient desires or needs therapy.

Absolute indications for intervention

• Urinary retention
• Upper urinary tract obstruction secondary to benign prostatic hyperplasia (BPH)
• Diminished renal function caused by BPH
• Gross hematuria due to BPH (although this can be managed with medical therapy with 5aR inhibitors)
• Recurrent urinary tract infections
• Bladder calculi
• Progressive deterioration of bladder function - Demonstrated by an increase in the amount of residual urine or decreased bladder muscle tone and pressure on cystometrogram (CMG) or pressure-flow studies
• Overflow urinary incontinence

Some men have silent prostatism in which serious deterioration of the bladder and/or renal function occurs with relatively few urinary symptoms.

Relative indications refer to the patient's symptoms and his desire to improve the clinical situation. Use the IPSS index to evaluate and follow the cases of these patients because the patient himself usually has difficulty recognizing changes in voiding, which often are subtle and somewhat variable daily.

After making the decision to intervene, determine next whether to alter the pharmacologic therapy or initiate some type of invasive procedure.

Interstitial laser coagulation therapy

• Interstitial laser coagulation (ILC) therapy is among the choices of invasive therapy.
• Most patients are not familiar with this particular method for treating BPH.
• Almost any patient who is a candidate for an invasive procedure is eligible for ILC.
• An advantage of this technique is that it can be offered to anyone regardless of age, symptoms, configuration of the prostate, or severity of symptoms.
• Usually, minimal blood loss occurs.
• Patients require only a short hospital stay, or the procedure can be performed on an outpatient basis.
• Patients do not experience any adverse effect on potency.
• The procedure can be performed with a regional or local anesthesia.
• Urologists can perform this procedure in their offices.
• Ensure that the patient is not taking anticoagulants during the preoperative period because of potential bleeding from the multiple prostate perforations.
• Some patients need to be able to manage a Foley catheter while at home, usually for 5-7 days.

Relevant Anatomy

Anatomy relevant to interstitial laser coagulation (ILC) therapy is assessed with a cystoscopic examination. The prostate consists of glandular elements embedded in a fibrostromal network with a rich vascular supply. Androgens, growth factors, and cytokines produced by the stromal cells mediate this interdependent relationship.

The development of benign prostatic hyperplasia (BPH) begins in a specific portion of the prostate, the transition zone, which encircles the urethra. This hyperplastic growth is initiated in men aged 30-35 years. Symptoms are thought to develop from the interaction among the following 3 components:

• The static component results from enlargement of the inner portion, or transition zone, of the prostate. This zone is adjacent to the urethra and develops into a hyperplastic adenoma.
• The second, dynamic component, involves the smooth muscles in the prostate, the prostatic capsule, the base of the bladder, the bladder outlet, and proximal portion of the urethra.
• The third component is the bladder muscle (detrusor), which responds to these changes in the prostate with a decrease in contractility, an increase in uninhibited contractions, or a combination of both. The detrusor becomes hyperplastic and increased fibrotic tissue diminishes the elasticity of the bladder.

Contraindications

Few absolute contraindications exist for this procedure. Relative contraindications are as follows:

• Coagulopathies that are not reversible
• Active infections
• Prostates larger than 80 g
• Patient inability to manage a catheter after surgery

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