AUTHOR INFORMATION	Section 1 of 11
Author Information Introduction Indications Relevant Anatomy And Contraindications Workup Treatment Complications Outcome And Prognosis Future And Controversies Pictures Bibliography

Author: Jonathan Rubenstein, MD, Staff Physician, Department of Urology, Northwestern University Medical School Coauthor(s): Kevin T McVary, MD, Associate Professor, Department of Urology, Northwestern University Medical School

Jonathan Rubenstein, MD, is a member of the following medical societies: American Urological Association

Editor(s): Bradley Fields Schwartz, DO, FACS, Director, Center for Urologic Laparoscopy and Endourology, Associate Professor of Urology, Department of Surgery, Southern Illinois University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; Laurence Klotz, MD, Professor, Department of Surgery, University of Toronto School of Medicine, Canada; J Stuart Wolf, Jr, MD, Director of Michigan Center for Minimally Invasive Urology, Associate Professor, Department of Urology, University of Michigan Medical Center; and Stephen W Leslie, MD, FACS, Founder and Medical Director, Lorain Kidney Stone Research Center, Clinical Assistant Professor, Department of Urology, Medical College of Ohio

	INTRODUCTION	Section 2 of 11
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As the population ages, a greater number of men are presenting with symptomatic benign prostatic hypertrophy (BPH). The criterion standard for treatment of BPH is the transurethral resection of the prostate (TURP). While, in general, this procedure is safe, patients require a spinal, epidural, or general anesthesia and several days of hospital stay. The potential morbidity and mortality limits the use of TURP in patients at high surgical risk. Potential complications include bleeding, infection, prolonged catheterization, TURP syndrome, and stricture formation.

Pharmacotherapy has been recommended as a first-line therapy for all patients with mild-to-moderate symptoms, although the long-term outcomes are not fully elucidated, patients must adhere to a strict medication schedule, and pharmacotherapy fails to reach outcome indicators as much as or as reliably as TURP. Patients choose pharmacotherapy because of the perceived reduced risk of adverse events and the desire to avoid surgery per se.

This trade-off of risk for efficacy is a common trend running through all elective treatments for BPH. Newer modalities have been aimed at providing alternatives to pharmacotherapy or watchful waiting. Patients' acceptability is large if they are offered a one-time method to treat lower urinary tract symptoms secondary to BPH and the method offers reduced risk and allows reliable efficacy equal to that of medical therapy.

One such method is transurethral microwave thermotherapy (TUMT). TUMT involves the insertion of a specially designed Foley-type catheter into the bladder, allowing a microwave antenna to be properly positioned within the prostatic fossa. Using microwaves to create heat for destruction of hyperplastic prostate tissue, this therapy is a potentially minimally invasive procedure associated with minimal morbidity and mortality. The goal of microwave therapy is to provide efficacious treatment with less patient risk than that of TURP. Early results show excellent symptomatic relief in as little as one outpatient session using only local anesthesia, although long-term follow-up data are not yet available. Based on the current literature, although TUMT apparently is associated with a lower anesthetic and surgical risk than TURP, it is associated with less improvement in urinary functioning. Note that TUMT is one of many medical and surgical therapies available for the treatment of BPH.

Clinical indications and treatment parameters for TUMT are still evolving as technology advances and more experience is gained. This article summarizes current knowledge of indications and efficacy of microwave therapy of the prostate.

History of the Procedure: Investigators have long sought safer and less invasive alternatives to surgical prostate resection for treatment of BPH. Recently, several new procedures and devices have been created and evaluated in an attempt to relieve bladder outlet obstruction and to improve urinary flow; these new methods include TUMT, transurethral laser incision of the prostate (TULIP), and transurethral needle ablation (TUNA), and each of these methods is associated with benefits and risks.

Special note should be made with regard to TUNA, which has a similar mechanism of action as TUMT. Both use radiofrequency waves to create heat in an attempt to destroy prostate tissue in situ. TUNA uses waves at 490 kHz while TUMT waves are 900-1100 kHz. Both can be performed in the office setting without the need for intravenous sedation, and both employ thermosensors in the urethra and rectum to monitor for excessive heat production. Unlike TUMT, TUNA applies the heat directly to the adenoma under direct vision. Two needles are deployed from the catheter tip and are directed alternatively at the right and left lobes of the prostate. TUNA produces necrosis of the adenoma while preserving the urethral mucosa.

TUNA is associated with a statistically significant improvement in symptoms scores, quality of life, urinary flow rate, and postvoid residual (PVR) after 1 year of follow-up. However, patients must be able to tolerate a rigid cystoscope in the urethra for as long as 30 minutes, and the follow-up data on TUNA are not as complete as for TUMT. Further specifics are beyond the scope of this article.

Applying heat to the prostate gland is not a new technique. In 1921, McCaskey used heat in the form of ultraviolet lamps to treat prostatism. In 1929, Corbus used diathermy probes for the same purpose. These therapies never became clinically accepted. In the 1980s, the use of heat to treat BPH regained clinical interest as alternatives to TURP were being explored. Studies revealed that normal prostate cells underwent necrosis when exposed to temperatures of 44-45ºC for 30 minutes. The modern use of microwaves has been credited to Yerushalami and associates, who, in 1985, applied microwaves by the transrectal route to treat patients with BPH who were poor operative candidates.

Microwaves, which fall within 300-3000 MHz wavelengths, are absorbed as they propagate through tissue, inducing local changes that produce heat. Higher frequencies are associated with more energy but lower tissue penetration. In TUMT, an external power source creates microwaves that are emitted at a frequency of 900-1100 MHz. The urethral antenna is directed towards the lateral lobes of the prostate. Tissue penetration leads to electromagnetic oscillations of free charges and the polarization of small molecules, such as water, resulting in the release of kinetic energy, which increases the temperature of the tissue. Finally, cell necrosis, vascular injury, and apoptosis ensue. Both the transrectal and transurethral route were used in an attempt to determine the optimal mechanism, duration of therapy, and wavelength frequency.

The first machines to undergo clinical trials used the transurethral route in a series of ten 1-hour sessions. These machines used software and instrumentation that allowed only a limited, and often interrupted, delivery of energy to the prostate. Intraprostatic temperatures reached 40-45ºC. Patients reported a subjective improvement in symptoms, although an objective improvement of voiding parameters was not observed. Histologic studies revealed that prostatic cells were not destroyed, but symptomatic improvement was proposed to be secondary to the destruction of the alpha-adrenergic nerve fibers around the prostate, leading to a change in the voiding reflex.

Further research revealed that temperatures greater than 45ºC were necessary to cause coagulative necrosis, protein denaturation, and tissue ablation to reliably destroy prostate cells. These cells slough away over a period of weeks to months. When exposed to 47ºC for 1 hour, apoptosis was observed in 76% of cells, and necrosis was observed in 14% of cells. Unfortunately, the urethral pain threshold was realized to be 45ºC. The introduction of urethral cooling allowed higher energy to be used, resulting in higher intraprostatic temperatures and increased tissue destruction. The term hyperthermia was coined to describe treatment with temperatures less than 45ºC, while thermotherapy was used to describe therapy with temperatures greater than 45ºC.

As prostate tissue was destroyed more reliably, the time of therapy was decreased. Antennae were improved to provide a concentric distribution of heat. Heat distribution now generally follows the anatomical borders of the transition zone, the main source of adenomatous tissue. Using thermotherapy, both objective and subjective parameters reflected significant improvement. Histologic examination of specimens revealed cell destruction but no reliable cavitation. Patients invariably had severe prostatic edema and urinary retention, requiring the use of a urinary catheter, which became standard practice after TUMT.

To improve outcomes even further, high-energy thermotherapy was introduced. Temperatures greater than 70ºC were reached, causing thermoablation of prostatic tissue. Unlike thermotherapy, prostatic cavities were observed on histologic sections, resulting in greater improvement in symptoms and objective parameters. However, unlike TURP, patients did not notice an immediate improvement but rather a gradual change over a period of months.

Problem: BPH is one of the most common diseases of the aging male. An estimated one third of men older than 50 years develop symptoms of prostatism, and 30% of these men eventually require surgery. Untreated, BPH can lead to significant morbidity due to physical obstruction of urinary outflow. Urinary stasis leads to an increased risk of urinary tract infections and urosepsis, detrusor dysfunction, bladder stones, and renal failure. Irritative voiding symptoms, such as frequency, urgency, and nocturia, cause severe interference in the quality of life due to loss of sleep, interruption of daytime activities, urge incontinence, anxiety, and a decreased perception of health.

TURP has been the criterion standard for treatment of BPH and, until recently, was the only widely accepted modality. This procedure, however, is associated with moderate morbidity and a known mortality rate. Because of the current practice of initially starting many patients on alpha antagonists, patients now presenting for TURP are older and have more comorbidities. The higher risk associated with these patients has been offset by better surgical technique, experience, and instrumentation.

Frequency: An estimated 50% of men have histologic evidence of BPH by the age of 50 years, which increases to 75% in men older than 80 years. In 40-50% of these patients, BPH becomes clinically significant. Adenomatous growth is believed to begin in persons younger than 30 years.

Numerous studies evaluate racial differences, but these studies have been difficult to interpret. The incidence of BPH in whites and blacks in the United States appears to be equal, but symptoms often appear earlier in blacks. An increased incidence of adenomatous hyperplasia occurs in black Americans as compare to blacks in Africa. A decreased incidence of BPH occurs in Chinese and Japanese people. Geographic differences as well as nutritional differences appear to explain these results.

Etiology: The normal prostate is composed of a combination of glandular, stromal, and smooth muscle cells. BPH is due to a proliferation of glandular elements, fibromuscular (stromal) elements, or both. Unlike prostate cancer, which invariably originates in the peripheral zone of the prostate, BPH is found in the transitional zone and the periurethral area.

The hyperplastic growth of prostate tissue is believed to be due, at least in part, to stimulation by dihydroxytestosterone (DHT), which is converted from testosterone by the action of 5-alpha reductase within the prostate. People with a congenital absence of 5-alpha reductase have ambiguous genitalia at birth, develop normal virilization, are capable of erections, and achieve ejaculation at puberty due to a testosterone surge, but these people are demonstrated to have a vestigial prostate.

The only known risk factors for BPH are aging and intact testes, the latter of which appears to be due not only to testosterone but to other factors that have not yet been elucidated.

Pathophysiology: BPH is a nodular, regional growth with a variegated gross appearance. Nodules of varying sizes may appear anywhere in the prostate, although they appear more commonly in the transitional zone and periurethral areas rather than peripherally. Nodules grow in nearly any direction, although the prostatic capsule acts somewhat as a barrier to outward growth. Therefore, as the nodules increase in size, they often compress urethral lumen. No correlation exists between the size of the prostate or prostatic nodules and urethral occlusion.

As urethral resistance to urinary flow increases, the bladder initially compensates by undergoing hypertrophy. Urinary flow parameters are maintained by a stronger detrusor contraction and hypertrophy of the detrusor muscle. Uncorrected, this initial adaptation leads to replacement of the smooth muscle cells with collagen, resulting in decreased compliance and poor bladder functioning. This eventually leads to bladder failure.

Clinical: The clinical presentation of patients with prostatic hypertrophy is varied. Patients may present with irritative voiding symptoms such as nocturia, urinary frequency, urgency, or dysuria due to bladder hypertrophy. Nocturia seems to be due to a loss of sensory inhibitions that are present while awake. Obstructive voiding symptoms, such as a weak urinary stream, double voiding, hesitancy, and a feeling of incomplete emptying, are more common when the bladder is no longer able to compensate for a chronic increased outlet obstruction. Patients also may present with a complication of prostatic hypertrophy, such as urinary tract infection, bladder stone formation, or renal failure. Abdominal pain may be due to a chronic high residual urinary retention. In these situations, evaluate the kidneys for hydronephrosis. Microscopic or gross hematuria may be due to BPH, although urothelial or renal tumors must be ruled out.

Realizing that many or all of these symptoms can be due to neurogenic voiding dysfunction, urethral stricture, urinary tract infection, a bladder stone, a foreign body, prostatitis and/or chronic pelvic pain syndrome, and altered fluid status due to multiple underlying medical diseases is important; all of these must be ruled out before treating BPH.

All eligible patients require a thorough history and physical examination. Clinical evaluation assesses the presence and degree of voiding dysfunction and/or the role played by BPH. History should include the presence, onset, progression, and severity of urinary symptoms of nocturia, hematuria, urgency, frequency, hesitancy, intermittency, and incomplete emptying. Focus questions on prior treatments for BPH such as alpha-blockade, herbal therapy, or TURP.

A past medical history should focus on the patient's past urologic history along with surgical risks and concomitant medical problems. Urologic history should include a history of sexually transmitted diseases, kidney stones, trauma, previous catheterizations, genitourinary cancer, renal insufficiency, neurologic disease, and neurogenic bladder. Medical conditions that may influence bladder functioning include diabetes and neurological diseases. Surgical risks predominantly are due to renal failure, coronary artery disease, and cerebrovascular disease. Medicines containing alpha sympathomimetics, such over-the-counter cold remedies, enhance bladder outlet obstruction. Discuss diet, fluid intake, sleeping habits, and complications of urinary retention with the patient. A family history should focus on a history of urologic cancer, and a social history should focus on risks for cancer such as a smoking history and occupational exposure.

The physical examination should be systematic and meticulous. Expand the physical examination if indicated by history and observations. Note the general appearance of the patient. Evaluate for masses and the presence or absence of a distended bladder with an abdominal examination. Evaluate for urethral stenosis or meatal stenosis with a genital examination and include a thorough evaluation of the genital structures. Focus the rectal examination on the anal area and rectal tone. Evaluate for rectal pathology. The prostate is evaluated for its size, laterality, consistency, landmarks, and the presence or absence of nodularity.

	INDICATIONS	Section 3 of 11
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Indications for TUMT are nearly identical to TURP. Indications include people with moderate-to-severe obstructive or irritative voiding symptoms, patients for whom medical therapy has failed, and people who choose not to be managed medically. However, most agree that patients with mild-to-moderate symptoms should be treated with medical therapy or minor interventions, reserving more definitive therapy for those with more severe symptoms.

Once a patient presents for more definitive therapy, carefully consider the type of surgery. As the criterion standard, TURP is offered to most patients. The potential advantages of microwave therapy over TURP include the relief of lower urinary tract symptoms with an in-office procedure using minimal anesthesia and a potentially rapid recovery. TUMT is considered in patients who prefer an outpatient setting rather than a hospital stay and for those who are at an increased surgical or anesthetic risk.

	RELEVANT ANATOMY AND CONTRAINDICATIONS	Section 4 of 11
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Relevant Anatomy: The urinary bladder is derived embryologically from the urogenital sinus. The detrusor musculature makes up the bulk of the bladder and is stimulated mainly by the parasympathetic nervous system. The ureters enter the bladder at the corners of the trigone. The prostate, which originates from the mesenchyme surrounding the urogenital sinus, is a compound tubuloalveolar gland whose base abuts the bladder neck and whose apex merges with the membranous urethra at the urogenital diaphragm. The normal adult gland is cone-shaped and is 4.4 cm in transverse diameter across the base, 3.4 cm in length, and 2.6 cm in anteroposterior direction. Its blood supply is from the prostatovesicular artery, a branch of the inferior vesical artery from the hypogastric artery.

The nerve supply is from the pelvic plexus, which travels with the prostatovesicular artery. Alpha-adrenergic nerves innervate the prostatic stroma, capsule, bladder neck, and periurethral area, causing contraction and increased outlet resistance. The prostate is divided into zones. McNeal described the most commonly used division, which distinguishes the anterior, peripheral, transitional, and central zones.

Contraindications: Several general contraindications to all prostatic surgeries exist, such as active urinary infection or known or suspected prostate or urothelial cancer. Consider each of these before a treatment plan is instituted. Patients with neurogenic bladder voiding dysfunction should have their underlying neurogenic problem evaluated and treated.

Contraindications specific to TUMT are evolving as the technology changes and outcomes are studied further. Patients with a history of TURP or pelvic trauma should not undergo TUMT because of potential alterations in pelvic anatomy. Patients with glands that are smaller than 30 g or a prostatic urethral length of less than 3 cm respond poorly to TUMT, as do patients with glands greater than 100 g and patients with a prominent median bar.

Other contraindications include patients with metallic implants, penile prosthesis, severe urethral stricture disease, Leriche syndrome and/or severe peripheral vascular disease, or an artificial urinary sphincter. Patients with pacemakers need clearance from their cardiologists concerning turning their pacemakers off during therapy, although performing TUMT in this group should be approached with apprehension.

Hip replacement is no longer a contraindication. Acute urinary retention previously was thought to be a contraindication to TUMT. However, high-energy TUMT has shown promising results in this population, although efficacy has yet to be determined. Patients presenting in retention tend to be ill, with greater comorbidities; thus, they might benefit from the less invasive nature of TUMT.