Transurethral Microwave Hyperthermia Research Articles

Transurethral Resection of the Prostate

Benign prostatic hyperplasia (BPH) causes a multitude of urinary symptoms as a result of obstruction of the bladder outlet. There are many phytotherapeutic and pharmacologic agents to treat BPH. BPH is more likely to be managed initially by primary care physicians and internists (49% of cases) than by urologists (37%) (1). Furthermore, minimally invasive techniques such as transurethral microwave hyperthermia (TUMT), transurethral needle ablation (TUNA), water-induced thermotherapy (WIT), and interstitial laser therapy have expanded the treatment options for BPH. Nevertheless, transurethral resection of the prostate (TURP) continues to be the mainstay of therapy and the gold standard surgical technique. In the United States, approx 25% of men are treated for BPH by the age of 80 yr, and more than 300,000 surgical procedures are performed annually for BPH. TURP is the second most commonly performed surgical procedure, at a cost estimated to be $2 billion (2). Despite the availability of pharmacotherapy and minimally invasive options, TURP remains a popular treatment for BPH because of its familiarity among urologists and superiority in treating the symptoms of prostatism, particularly urinary retention.

Management of prostatitis.

Prostatitis is a common clinical entity with a prevalence rate of 5-9% and accounts for over 2 million hospital visits annually in the USA. It is traditionally classified into acute bacterial, chronic bacterial, abacterial prostatitis and prostatodynia. The recent consensus conference of the US National Institute of Diabetes and Digestive and Kidney Diseases in 2000 resulted in renewed interest in the prevalence, etiology, pathogenesis and treatment of the prostatitis syndromes. In this review, we present the contemporary knowledge and experience regarding the etiology, classification, evaluation and treatment of this condition including the role of transurethral microwave hyperthermia and transurethral needle ablation.

Transurethral Microwave Hyperthermia in the Treatment of Chronic Nonbacterial Prostatitis

Chronic nonbacterial prostatitis is an ill-understood and difficult-to-diagnose disease. Symptoms of chronic nonbacterial prostatitis are similar to those of chronic prostatitis and include low back pain, frequency, dysuria, perineal discomfort, and painful ejaculation. In view of uncertainty about etiology, treatment of chronic nonbacterial prostatitis remains speculative. Most treatment is aimed at relieving symptoms and not at curing the disease. Because of the troublesome nature of chronic nonbacterial prostatitis and the poor results obtained from traditional treatment methods, a new modality of transurethral microwave hyperthermia was investigated. Six patients were treated from January 1994 through June 1995 by use of transurethral microwave hyperthermia. These men were treated four times during a 2-week period. Their average symptom score decrease was 74.9% and was associated with minimal morbidity. Based on this result, it is concluded that transurethral microwave hyperthermia is a safe and effective treatment modality for chronic nonbacterial prostatitis.

Transurethral Microwave Hyperthermia in the Treatment of Chronic Nonbacterial Prostatitis

Transurethral Microwave Hyperthermia in the Treatment of Chronic Nonbacterial Prostatitis

Thermoregulation in the canine prostate during transurethral microwave hyperthermia, part II: Blood flow response

Recent studies on transurethral-applied local hyperthermia in both the canine and human prostate have revealed significant effects of natural thermoregulation on the therapeutical results in the prostate. Using a thermal clearance method, blood perfusion rates were measured within different regions in the canine prostate under normal and hyperthermic conditions. It has been found that the canine prostatic blood perfusion is strongly linked to the geometrical location within the gland, the local tissue temperature, and the imposed thermal dosage. Results from this research are expected to provide a better understanding of the thermoregu latory behaviour in the canine prostate, and thus lay an important foundation for predicting tissue temperature in the human prostate during transurethral microwave hyperthermia.

Thermo Regulation in the Canine Prostate During Transurethral Microwave Hyperthermia, Part I: Temperature Response

In this research, experiments were performed to study thermoregulation in the canine prostate during microwave hyperthermia. The transurethral thermal therapy (T3) system provided by Urologix, Inc. was used to impose microwave heating in the canine prostate. Five types of temperature responses to different microwave power levels as time varies, including both damped and sustained oscillatory temperature responses, have been observed. Decreases in prostatic tissue temperature during the microwave heating are believed to be caused by the increase in local blood flow stimulated by tissue temperature elevations. In this study, the characteristic temperatures and time associated with each response. This work will help to provide a better understanding of how tissue temperature is regulated within the canine prostate during transurethral microwave hyperthermia. Results of the present study offer an experimental foundation for a more detailed theoretical analysis on the temperature distribution based on the power input and local blood perfusion.

Transurethral microwave hyperthermia in the treatment of chronic nonbacterial prostatitis.

Chronic nonbacterial prostatitis is an ill-understood and difficult-to-diagnose disease. Symptoms of chronic nonbacterial prostatitis are similar to those of chronic prostatitis and include low back pain, frequency, dysuria, perineal discomfort, and painful ejaculation. In view of uncertainty about etiology, treatment of chronic nonbacterial prostatitis remains speculative. Most treatment is aimed at relieving symptoms and not at curing the disease. Because of the troublesome nature of chronic nonbacterial prostatitis and the poor results obtained from traditional treatment methods, a new modality of transurethral microwave hyperthermia was investigated. Six patients were treated from January 1994 through June 1995 by use of transurethral microwave hyperthermia. These men were treated four times during a 2-week period. Their average symptom score decrease was 74.9% and was associated with minimal morbidity. Based on this result, it is concluded that transurethral microwave hyperthermia is a safe and effective treatment modality for chronic nonbacterial prostatitis.

Thermal therapy in the treatment of benign prostatic hyperplasia

After transurethral and transrectal microwave hyperthermia were found to be no more beneficial in the treatment of benign prostatic hyperplasia than a sham treatment, transurethral microwave thermotherapy has emerged as a viable minimally invasive treatment alternative in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Several well conducted, randomized, controlled trials demonstrated superiority over sham treatment. Most recent efforts are directed at identifying pretreatment outcome predictors and the best candidates for this therapy.

Optimization of transurethral hyperthermia: Number of treatments

Objective. The optimal number of transurethral microwave hyperthermia (TUHT) treatments in patients with moderate to severe symptoms of benign prostatic hyperplasia (BPH) is not known. This study was designed to compare TUHT efficacy with the use of three versus six treatments. Methods. In a Phase II prospective trial during a three-month period, 28 poor surgical risk patients with moderate to severe prostatism were randomized to receive three or six TUHT sessions. TUHT treatments were given on an outpatient basis without sedation or anesthesia for sixty minutes at 915 MHz with the temperature controlled on the urethral surface at 45°C. Results. Subjective improvement was obtained in 7 (50%) patients receiving three TUHT treatments and in 12 (86%) patients receiving six treatments. A greater degree of improvement in total symptom score (P = 0.01) and obstructive (P = 0.01) and irritative (P = 0.04) symptoms was also recorded in the 14 patients receiving six treatments compared to those treated with three TUHT sessions (P = 0.01). A posttreatment improvement in objective study parameters was recorded for both treatment groups. The 14 patients treated with six TUHT sessions, however, showed a better improvement in peak flow rates (51 % vs. 8.4%, P = 0.003) and postvoiding residual volume compared to the 14 patients treated with three TUHT sessions (P = 0.10). Treatments were very well tolerated and no clinically significant toxicity was recorded. Of the 9 study patients who failed to respond to treatment, 1 patient was successfully retreated with TURP while 8 patients required an indwelling catheter. Conclusions. In TUHT in poor surgical risk patients with BPH with the temperature controlled at 45°C, six treatments were superior to three treatments, based on a higher incidence of subjective and objective improvement.

New trends in the treatment of benign prostatic hyperplasia and carcinoma of the prostate.

Benign prostatic hyperplasia (BPH) is a very common condition affecting over 800,000 American males each year. A standard, effective, and well-proven therapy is prostatectomy. This surgical procedure is used to treat, in the United States, approximately 400,000 BPH patients annually. Major treatment benefit is expected in 70% to 80% of patients. Complications are seen in 20% of the surgically treated patients. Due to the advanced age of BPH patients and the presence of other serious coexisting medical problems, surgical therapy may be difficult to utilize. These patients, who present a high risk for surgery, are in need of alternative treatments. Alternative therapy in BPH patients with clinically important symptoms and signs of urinary outflow obstruction include treatment with pharmacological agents, balloon dilatation, laser beam therapy, transurethral thermal therapy, transrectal microwave hyperthermia, and transurethral microwave hyperthermia. These alternative treatment modalities are currently under intensive study. These new treatment modalities ultimately must be compared with the standard treatment, which is prostatectomy. Due to the unpredictable natural history of BPH, it is desirable that each Phase III study should contain a no-treatment observation-only arm. Adenocarcinoma of the prostate (CaP) has become a tumor, which first in frequency, and second in importance in cancer mortality statistics of American males. Local tumor control rates and long-term survivals, with radical prostatectomy or radiation therapy, have been excellent. There was, however, recent concern regarding a high incidence of microscopic local tumor recurrence following a definitive course of irradiation. Deep regional or intracavitary hyperthermia (HT) with phase steering may be of value as an adjuvant treatment to radiotherapy. This HT may increase the incidence of local tumor control obtained with radiotherapy. Phase I-II clinical studies are currently underway.

Relationship of response to transurethral hyperthermia and prostate volume in BPH patients

A response to transurethral microwave hyperthermia (TUHT) at 915 MHz and its relationship to prostate volume was examined in 63 poor surgical risk benign prostatic hyperplasia (BPH) patients. All patients had moderate-to-severe obstructive signs and symptoms, and received ≥5 TUHT one-hour sessions. Treatment temperature was controlled on the urethral surface at 45°C ± 1°C. Follow-up ranged from twelve to forty-four months (mean 18 months). The mean prostate volume was 57 cc (range 10–301 cc). There were 40 patients (63 %) with prostate volume ≤50 cc and 23 (37 %) with a volume >50 cc. Treatment failure was seen in 6 patients (10 %). It was 10 percent in 40 patients with smaller glands and 9 percent for those 23 with larger prostates, N. S. at p = 0.49. Subjective treatment response was seen in 58 patients (92 %). It was 90 percent for the 40 patients with ≤50 cc prostates vs. 96 percent for the 23 with >50 cc prostates, N. S. at p = 0.75. This study suggests that the initial prostate volume is not an important parameter predicting response to TUHT.

Transurethral Hyperthermia for Benign Prostatic Hyperplasia Patients with Retention

From 1989 to 1990, 32 poor surgical risk patients with urinary retention were treated with transurethral microwave hyperthermia at the department of urology, University of Leuven in Belgium. Mean patient age was 73 years (range 58 to 90 years) and mean duration of retention was 4 weeks (range 3 to 12 weeks). Followup ranged from 13 to 82 weeks, with a mean of 31 weeks. Bilobar or trilobar hyperplasia was diagnosed in 25 patients (78%), while 7 (22%) had median lobe or median bar hypertrophy. The mean prostatic volume was 52 cc (range 25 to 150 cc).Transurethral microwave hyperthermia was given with a helical antenna at 915 MHz. once or twice per week. The mean number of transurethral microwave hyperthermia sessions was 8.9 (range 5 to 10). Each session consisted of a 60-minute treatment at a mean maximum temperature of 45.4C (range 43.7 to 47.2C), average temperature 43.9C (range 42.7 to 45.5C) and minimum temperature 42.0C (range 40.2 to 43.0C). The temperature was continuously monitored, including thermal mapping in all patients.Of the 25 patients who presented with bilobar or trilobar hyperplasia 18 (72%) were catheter-free for the duration of followup. Of the 7 median lobe or median bar patients 1 (14%) showed sufficient improvement to warrant catheter removal. This patient, however, had recurrent retention 4 months after transurethral microwave hyperthermia. In patients with bilobar and trilobar hyperplasia a strong correlation was observed among maximum temperature (p = 0.0006), average temperature (p = 0.0033) and treatment response. As expected, no such correlation existed between minimum temperature and response to treatment (p = 0.56). Our study has again demonstrated therapeutic activity in patients with benign prostatic hyperplasia treated with transurethral microwave hyperthermia. A new finding was a strong correlation between temperature and response.

Transurethral microwave hyperthermia in benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a common disease affecting past middle-aged males. Surgical treatment has been successfully used since the early 1900s. Currently, nonsurgical treatment modalities are under intensive study in BPH patients who have relative contraindications to surgery. Transurethral microwave hyperthermia (TUHT) is one of these modalities under study. TUHT has been applied in five to ten treatment sessions. The treatments were well tolerated with no major toxicity being reported. In BPH patients with predominance of median lobe or median bar enlargement the treatment efficacy was reduced to 30%. The effectiveness of TUHT was of particular importance in patients who had urinary retention. In this group 72% had normal voiding for 12 months or longer. A strong correlation between applied temperature and response to treatment was demonstrated. Current efforts are directed toward optimization of technique and treatment schedule. A phase III prospective randomized trial is required to define the role of TUHT in the management of BPH patients.

A Comparison of Transurethral and Transrectal Microwave Hyperthermia in Poor Surgical Risk Benign Prostatic Hyperplasia Patients

From 1987 to 1989, 36 poor surgical risk patients with benign prostatic hyperplasia (BPH) were treated with transrectal or transurethral microwave hyperthermia. Most of the 36 patients treated (85%) had severe signs and symptoms of urinary outflow obstruction. Of the patients 22 (61%) underwent transrectal and 14 (39%) underwent transurethral hyperthermia. Followup ranged from 10 to 28 months (mean 19 months) for the transrectal hyperthermia group and 7 to 16 months (mean 10 months) for the transurethral hyperthermia group. The patients were given 6 hyperthermia sessions of 30 minutes each with the temperature controlled on the rectal or urethral surface at 45C. Hyperthermia was well tolerated with mild acute toxicity and no late complications were observed. In the important subjective and objective parameters, major improvement was noted more frequently in the 14 transurethral than in the 22 transrectal hyperthermia treated patients (p < 0.05). The Food and Drug Administration severity score, prostate volume, post-voiding residual volume and urethral flow showed substantial improvement in 79, 86, 79 and 79%, respectively, of the 14 transurethral hyperthermia treated patients compared to 41, 45, 82 and 82%, respectively, for the 22 transrectal hyperthermia treated patients. A prospective randomized trial comparing transrectal and transurethral hyperthermia is required to define the role of each treatment mode in patients with BPH.

Interstitial Temperature Measurements During Transurethral Microwave Hyperthermia

Microwave hyperthermia is presently being investigated as a treatment for alleviating the symptoms of urinary outlet obstruction associated with benign prostatic hyperplasia. Two clinical techniques using intracavitary microwave applicators are being evaluated for safety and efficacy at various institutions. The transrectal technique uses a directional microwave radiator that is inserted into the rectum adjacent to the prostate. The transurethral approach uses a symmetrically radiating applicator located within the prostatic urethra. Transrectal prostatic heating techniques require surface cooling to prevent hazardous temperatures in the intervening rectal mucosa. Since trans-urethral applicators radiate from within the prostatic urethra, heating is confined to the obstructive tissue immediately surrounding the applicator. Concern has been expressed regarding the possibility of thermal injury to the prostate and adjacent rectum during transurethral hyperthermia treatment. In this report we present interstitial temperature measurements of prostatic and rectal temperatures in 5 patients. Temperature was observed to decrease at a rate of about 6C/cm. outward from the applicator. No clinically significant temperature increase was observed beyond 1cm., outside the prostatic capsule or in the rectal mucosa.

Histopathology of prostatic tissue after transurethral hyperthermia

Histopathological changes were studied in four patients who had moderate to severe urinary outflow obstruction due to benign prostatic hyperplasia (BPH) and were treated with transurethral microwave hyperthermia (TUMH). All these patients received TUMH with a helical antenna using a BSD 300 unit. The temperature was controlled on the urethral surface at 45 degrees C +/- 1 degree C. Each treatment session lasted 70 min at this temperature. Histological changes were periurethral, extending up to 6 mm radially and 4-5 cm longitudinally. They were symmetrical and most severe in the immediate periurethral zone. The severity and distribution of these histological changes correlated well with the thermal profile of the helical antenna. Acute changes, observed 24-48 h following administration of a single TUMH session, consisted of periurethral oedema, parenchymal haemorrhages and occasional, partial small-vessel thrombosis. Selective coagulation necrosis of the parenchymal smooth muscles with sparing of smooth muscle fibres in the vessel walls was noted. Histopathological changes found in patients 7 or 26 days following the administration of 10 TUMH treatments given twice-weekly for 5 weeks showed more severe and deeper lesions. They consisted of interstitial haemorrhages, complete obliteration of blood vessel lumina due to thrombosis and further evidence of coagulation and haemorrhagic necrosis. Evidence of a reparative process with ingrowth of granulation tissue in various stages of organization was clearly demonstrated. The effect of TUMH on BPH-obstructed urethra is probably expressed through selective shrinking and retraction of the periurethral prostatic parenchyma due to organizing localized tissue necrosis and cicatrization. Details of this complex process will be presented.

Transurethral microwave hyperthermia: An alternative treatment for prostadynia?

A total of 15 patients with severe symptoms of prostadynia who were refractory to therapy were treated with transurethral microwave hyperthermia (TUHT) in a phase I trial. All patients had pain as the predominant symptom, 9 (60%) patients gave a history of psychological problems while frequency, urgency, dysuria, nocturia, and impotence were less common symptoms. Treatment consisted of TUHT at 915 MHz given weekly for 5 weeks with a total of 68 treatment sessions and a mean of 4.5 treatments per patient. Each treatment lasted for 60 minutes. The aim was to increase the temperature measured on the urethral surface to greater than or equal to 44 degrees C. T mean for all sessions was 45.5 degrees C. In 91% of treatments, the temperature was greater than or equal to 44 degrees C. Treatment was well tolerated in 87% patients and acute toxicity was mild. Of the 15 patients treated, 2 (13%) did not complete the treatment course due to discomfort during TUHT. Good treatment response, manifested by complete pain relief and a decrease in dysuria, was noted in 7 (47%) patients. A higher (greater than or equal to 46 degrees C) treatment temperature correlated well with good response, P less than .01. Similarly, relief of pain correlated well with the absence of a history of psychological problems, P less than .01. A decrease of obstructive micturition problems was noted in 5 of the 7 patients who had this upon presentation. This study showed evidence of therapeutic activity with the use of TUHT in patients with prostadynia refractory to therapy. The response obtained was limited to less than one-half of the patients. Complete pain relief was obtained in 4 (27%) patients. It is of interest to note that patients who had major benefit did not show evidence of psychological problems and were able to tolerate higher treatment temperatures. The latter could suggest a temperature-related response.

Treatment response with transurethral microwave hyperthermia in different forms of benign prostatic hyperplasia: A preliminary report

During a 7-month period, 79 patients with benign prostatic hyperplasia (BPH) were treated with 915 MHz transurethral hyperthermia (TUHT). All patients had obstructive and irritative signs and symptoms which warranted surgical treatment considerations. Of the 79 patients treated, 31 had follow-ups of 12 months or longer and seven additional patients experienced treatment failure requiring surgical management. These 38 patients were studied to evaluate the relationship of treatment response to the pretreatment prostatic morphology assessed during cystoscopy. There was a well-balanced distribution of patients regarding the important pretreatment characteristics in different morphological types of prostatic hypertrophy. These important characteristics included: prostate volume, postvoiding residual volume, mean peak flow rate, and mean symptom score on the FDA scale. The study patients were scheduled to receive five 60-min TUHT sessions with temperature controlled on the urethral surface at 45.5 degrees C. The treatment were well tolerated and administered on an outpatient basis without sedation or anesthesia. There was a significant difference in the incidence of major improvement in patients with lateral lobe hyperplasia and those with median lobe enlargement, 73 vs. 30%, P = 0.018. From this study, it appears that BPH patients who are found at cystoscopy to have a predominance of median lobe hypertrophy should, perhaps, be selected for treatment other than TUHT. A Phase I study utilizing a modified transurethral applicator to accommodate the specific problem of patients with median lobe hyperplasia is currently being planned.

Transurethral Microwave Hyperthermia for Benign Prostatic Hyperplasia: Preliminary Clinical and Pathological Results

Transurethral microwave hyperthermia is a new conservative treatment modality for benign prostatic hyperplasia. We treated 15 patients with 915MHz. microwaves delivered transurethrally by a helical applicator. Of the patients 12 showed substantial objective and subjective improvement of obstructive outflow parameters. Significant improvement in objective study parameters included increased mean flow rate (p <0.00021), decreased mean residual volume (p <0.00001) and decreased mean prostatic volume (p <0.0077). Analysis of patterns of failure showed chronic bladder atony, prostate asymmetry and middle lobe configuration as important factors that could explain the failure of hyperthermia in 3 patients. Toxicity was mild, consisting of bladder spasms, perineal pain, dysuria and hematuria. Hyperthermia-induced pathological changes in prostatic tissues, causing periurethral shrinking and secondary dilatation of the prostatic urethra, are described.The reported clinical results of this phase I study are preliminary due to the short followup. A phase II study to optimize transurethral hyperthermia currently is underway. A phase III study is to be phased in comparing hyperthermia with transurethral resection of the prostate.