Local hyperthermia for prostate cancer.

Hyperthermia for treatment of cancer is known to be beneficial both in itself and in conjunction with other forms of treatment, particularly radiotherapy. We have developed a new machine for local hyperthermia (41-44 degrees C) to the prostate, by transmission of microwaves (915 MHz) via a rectal probe. Patients were treated on an outpatient basis and did not require any anesthesia or sedation. There were no complications. Good results, measured by local control, disappearance of malignancy, relief of obstructive symptoms and pain, have been obtained in a series of 44 cases. More studies with this promising new modality are in progress.

Diseases of prostate treated by local microwave hyperthermia.

A new method is described for the treatment of diseases of the prostate with local hyperthermia applied transrectally by microwaves. A series of 500 treatment sessions given to 74 patients with 14 controls, is reported. Thirty patients had advanced cancer of the prostate, 37 had benign hyperplasia and were unsuitable for surgery, and 21 had chronic prostatitis. Marked objective and subjective improvement was noted in the majority in twenty-four months of follow-up.

Local hyperthermia to canine prostate. A pilot study.

Repeated treatments of localized deep microwave hyperthermia were given to a series of dogs by means of a 915 MHz, water-cooled skirt-type applicator. The applicator was inserted into the rectum and directed toward the prostate in order to heat it by means of the absorbed microwaves while keeping the rectal wall at a lower temperature by surface cooling of the applicator itself. Sessions were given for different lengths of time ranging between ninety minutes and five hours, during which the prostate temperature was kept at 42.5 degrees C (+/- 0.5 degrees C) or 44.5 degrees C (+/- 0.5 degrees C). Three-dimensional temperature distributions in the prostate were measured accurately and verified by a Luxtron Fluoroptic Unit. Temperatures were constantly monitored in the rectal wall and in the prostatic urethra. Thorough and systemic follow-up was done before, during, and after each treatment, and the observations are reported. Two interesting preliminary observations were made: (1) differential blood counts showed significantly monocytosis following the treatments and lasted for at least one week, and (2) values of creatinine phosphokinase (CPK) and serum glutamic oxaloacetic transaminase (SGOT) were found to rise irreversibly in those animals which were later found to have definite histopathologic evidence of localized necrotic damage.

Reduced semen quality caused by chronic abacterial prostatitis: an enigma or reality?

OBJECTIVE: To investigate whether there is an inter-relationship between chronic abacterial prostatitis and potential infertility. DESIGN: As part of the eligibility studies for hyperthermia treatment for chronic abacterial prostatitis patients, a large number of chronic prostatitis patients were referred to us from peripheral outpatient clinics. Sperm analysis was a routine portion of the eligibility studies. To exclude bacterial prostatitis, urine cultures, expressed prostatic secretion, and semen cultures were performed. The patient population was not differentiated on the basis of those suffering from either nonbacterial prostatitis or prostatodynia according to the commonly accepted classification. The control group was the laboratory normal standard group. SETTING: Normal human volunteers in an academic and clinical research environment. PATIENTS: The first group includes 86 patients suffering from long-standing (1 to 20 years) chronic abacterial prostatitis, according to the commonly accepted classification, with a mean age of 39.9 +/- 9.5 years. The second group includes 101 normal fertile men with a mean age of 31.4 +/- 5.5 years. INTERVENTIONS: The routine semen analysis performed included biochemical tests of seminal plasma, bacteriology, and light microscopy. MAIN OUTCOME MEASURE: The original hypothesis was based on a reduction in semen quality in these patients caused by chronic abacterial prostatitis. Measurements for sperm motility parameters, morphology characteristics, prostate markers, and white blood cells (WBC) were designed accordingly. RESULTS: Statistical comparisons of the two groups showed that several sperm motility parameters, morphology characteristics, prostate markers, and WBC are outside of the normal value ranges in the chronic abacterial prostatitis group. In addition, there is a correlation between the duration of the disease and two important sperm analysis variables: increased prostatic markers and appearance of sperm morphological defects. CONCLUSION: From the results obtained, the high incidence of secondary infertility in these patients may be explained.

Chronic abacterial prostatitis and hyperthermia. A possible new treatment?

A group of 45 patients with chronic abacterial prostatitis or prostatodynia underwent 6 weekly, 1-hour sessions of local deep microwave hyperthermia (42.5 +/- 0.5 degrees C) to the prostate. All patients had a long history of symptoms typical of the condition. They all failed to respond to a variety of conventional treatments administered over several years by various specialists. Each patient served as his own control before and after the hyperthermic treatment. The results of this study are encouraging: 25% showed a sustained and complete loss of symptoms and 50% had a partial response; the remaining 25% reported no improvement. These results open up new possibilities in the treatment of this condition, which has so far responded poorly to conventional therapy.

Hyperthermia in the treatment of prostate cancer.

Hyperthermia-the sustained heating of tissues to temperatures of 42 degrees C to 43.5 degrees C--increasingly is being studied by scientists as a new tool to destroy cancer cells, either alone or in conjunction with other well established forms of treatment, such as radiotherapy and chemotherapy. Many studies on tissue cultures, on animals and also on humans, have established the fact that this new nonconventional adjuvant form of treatment is actually effective. Progress is being made in the development of the necessary technology for delivering the desired and controlled form of heat to the diseased site, while protecting the surrounding healthy tissues from irreversible damage. Initial clinical trials in this direction are very promising and seem to offer new avenues in the methods of treatment for cancer of the prostate.

The mechanism of human NK cell-mediated cytotoxicity. Mode of action of surface-associated proteases in the early stages of the lytic reaction.

The possible involvement of cell surface-associated proteolytic enzymes in human NK cell-mediated cytotoxicity and the mechanism by which such enzymes exert their activity have been studied. The treatment of intact cells with 3H-DFP under restricted conditions that predominantly bind surface-associated enzymes resulted in the labeling of five to six enzyme bands. Among these were a 35,000-dalton enzyme, which may be a previously identified trypsin-like proteinase engaged in cytotoxicity, and a 58,000-dalton elastase. The latter seems not to be involved in the reaction, as potent inhibitors of this enzyme have negligible effect on cytotoxicity. Of the membrane-associated enzymes, those engaged in cytotoxicity seem to be concealed from the external environment, as pretreatment of the effector cells with protease inhibitors such as trasylol and PMSF have no effect on the reaction. Immediately upon addition of the target cells and the initiation of cytotoxicity, the reaction becomes highly sensitive to inhibitors for a limited time interval of 2 to 5 min when trasylol is employed and 5 to 10 min when TPCK is the inhibitor, suggesting that target cell binding triggers the exposure of the enzymes to the external environment, rendering them accessible to the inhibitors. This short sensitivity period parallels the interval in which the reaction is sensitive to the microfilament inhibitor cytochalasin B. As the reaction proceeds, it becomes increasingly resistant to inhibitors of both proteolysis and cytoskeleton, at the same time suggesting that microfilament action and the unraveling of proteases may be processes that bear a close linkage with one another. The surface-associated elastase on the other hand maintains a constitutive mode of activity distinctive and unrelated to that of enzymes engaged in cytotoxicity. These findings suggest the existence on the surface of the NK lymphocyte of a mechanism that associates the receptor for target cells with an array of enclaved proteolytic enzymes via microfilaments. The resting cytotoxic structures become activated as the receptor attaches to the target cell, triggers the exposure of the proteolytic moiety, and initiates the lytic phase of the reaction.

Further observations on the use of local hyperthermia for the treatment of diseases of the prostate in man.

Hyperthermia - the sustained controlled heating of tissues to 42-43 degrees C - is being studied and used as a means of treatment, particularly to selectively destroy malignant cells. This may be achieved by heat alone, or in conjunction with other forms of treatment, such as radiotherapy or chemotherapy, thanks to a synergistic effect obtained. A new microwave apparatus has been designed and developed which permits precise, controlled and safe hyperthermic treatment of the human prostate. Following extensive laboratory and experimental studies, a first series of treatments on humans has been carried out. Initial observations on our first 192 treatments, on 32 patients, are reported.

Histopathological observations in the canine prostate treated by local microwave hyperthermia.

A large series of repeated experiments were performed applying localized microwave hyperthermia to the prostate in dogs using a new water-cooled skirt-type antenna [1], operating at 915 MHz, as part of a new hyperthermia apparatus being developed for the treatment of the prostate in humans. The prostate gland of 20 male dogs was heated repeatedly under general anesthesia, at temperatures between 40 degrees C and 47 degrees C, and for different lengths of time up to 10 h. The prostate and other tissues were evaluated histopathologically following treatments. Invariably, all treatments by hyperthermia of the prostate caused a mononuclear inflammatory infiltration in the interstitium and polymorphonuclear infiltration in the glandular elements. Permanent tissue damage was found to be time-and temperature-dependent. Heating at 42.5 degrees C (+/- 0.5 degrees 5C) for up to 1.5 h was found to be harmless and could be safely repeated with our equipment. This study was part of a preclinical evaluation of a new antenna and apparatus.

Changes in the sexual behavior of couples after prostatectomy. A prospective study.

Sexual behavior after prostatectomy was observed in 90 couples, with a follow-up of 3-6 years. Retropubic prostatectomy was performed on 53 patients (58.7%), transvesical prostatectomy on 12 patients (13.7%), and transurethral prostatectomy on 25 patients (27.7%). In order to have a reliable figure of the sexual behavior after surgery, all the couples underwent personal interviews separately before and 3-6 years after surgery. The interview included 4 main subjects: erection allowing sexual intercourse; antegrade ejaculation; orgasm, and libido. The separate identical double interviews were performed in order to achieve a high reliability in answer to sexual performance, this being the main unsolved question in previous studies. The results of the interviews were assessed by a computer-processing program and statistically analyzed. Our results imply that prostatectomy has an unfavorable influence on sexual activity: 33% of the potent preoperative patients became impotent after surgery.

Experience with bacillus Calmette-Guérin in patients with superficial bladder tumors. Value of monocyte activation in intravesical bacillus Calmette-Guérin therapy.

Twenty-four patients with transitional cell carcinoma of the bladder, who had failed thiotepa therapy, were subjected to immunotherapy with intravesical bacillus Calmette-Guérin (BCG) by a modification of the Morales protocol. The results show a marked decline in the number of recurrent tumors following BCG immunotherapy. From a cumulative recurrence of 1 in 8.3 months, recurrences declined to 1 in 82 months. In parallel with the clinical follow-up, the level of the in vivo activation of peripheral blood monocytes of the treated patients, as a result of immunostimulation with BCG, was monitored by the quantitation of oxidative burst products released by the cells. The oxidative burst capacity of peripheral blood monocytes were found to undergo an increase of 80-140% in 5 of 10 patients tested. The patients with a high level of activation of peripheral blood monocytes did not have tumor recurrence while 3 of the 5 patients who did not show an increase in the oxidative burst had recurrent tumors. The possibilities for utilizing the oxidative burst test as an early indicator for distinction between patients who will respond to BCG immunotherapy and nonresponders is discussed.

Local hyperthermia for treatment of carcinoma of the prostate: a preliminary report.

Following extensive experiments on animals, we have concluded a study on the treatment of 15 patients with prostatic carcinoma using localized deep microwave hyperthermia (LDMWH; 2.45 GHZ), either alone or in combination with radiotherapy or hormonal therapy. The results of this pilot trial were encouraging and are herewith presented. A total of 146 LDMWH treatments were given. All patients tolerated the treatments well, and there were no complications; the condition of the rectal mucosa was checked routinely by rectoscopy. A pronounced and rapid subjective and objective response was recorded in all cases, as noted by reduction in tumor size, regression of ureteral or urethral obstruction, disappearance of pelvic pain and improvement in well being. LDMWH was effective by itself and appeared to potentiate the effects of radiotherapy or hormonal therapy. Although LDMWH seems to be a promising and safe new method of treatment of prostatic cancer, either alone or in combination with other accepted forms of therapy, more controlled studies, which are at present underway, are needed to draw more definite conclusions.

Local hyperthermia of the prostate gland for the treatment of benign prostatic hypertrophy and urinary retention.

Local hyperthermia of the prostate was used to treat 72 patients who had an indwelling catheter because of urinary retention caused by benign prostatic hypertrophy. One month after completion of treatment 50% of patients were able to dispense with the catheter and 1 year later 40% remained catheter-free. The best results were achieved in patients who underwent 6 to 10 treatment sessions in conjunction with cyproterone acetate 50 mg tid administered during the treatment period only.

Local thermotherapy of the benign prostate: a 1-year follow-up.

Local hyperthermia to the prostate has initially been found to be of considerable beneficial value in cancer of the gland and later also in benign prostatic hypertrophy (BPH) and in chronic prostatitis. The Prostathermer has been especially developed and used for this purpose. 124 patients with BPH, who have been treated by this method, were reevaluated after 1 year. This thermotherapy was well tolerated, and no noticeable complications were encountered. A sustained definite improvement in objective and subjective obstructive symptoms and signs was seen in 51% of the cases. Such definite and persistent improvement was best obtained when treatments were performed twice weekly for 60 min over a period of 3 weeks. Those patients with the more severe obstructive symptoms fared best. A full explanation for the effectiveness of this treatment of BPH has yet to be found. Although local hyperthermia cannot, at this stage, be considered as a radical form of treatment of BPH, it may offer definite relief to about 50% of the cases, particularly to those unwilling or unsuitable for surgery.

Combined local bladder hyperthermia and intravesical chemotherapy for the treatment of high-grade superficial bladder cancer.

OBJECTIVES: To evaluate the effectiveness of combined local bladder hyperthermia and intravesical chemotherapy for the treatment of patients with high-grade (G3) superficial bladder cancer. METHODS: Patients with G3 bladder tumors (Stage Ta or T1) were treated with combined intravesical chemotherapy with mitomycin-C and local radiofrequency hyperthermia of the bladder wall. The patients were treated with either a prophylactic protocol (40 mg mitomycin-C) after complete transurethral resection of all tumors or with an ablative protocol (80 mg mitomycin-C) when visible tumor was seen on video-cystoscopy or bladder biopsies were positive for carcinoma in situ. RESULTS: Combined chemo-thermotherapy was administered to 52 patients with high-grade superficial bladder cancer (40 patients with Stage T1 tumor, 11 with Ta, and 3 with concomitant or isolated carcinoma in situ). At a median follow-up of 15.2 months (mean 23, range 6 to 90), no stage progression to T2 or disease-related mortality had occurred. The bladder preservation rate was 86.5%. The prophylactic protocol was administered to 24 patients. After a mean follow-up of 35.3 months, 15 patients (62.5%) were recurrence free. The bladder preservation rate was 95.8%. The ablative protocol was administered to 28 patients. Complete ablation of the tumor was accomplished in 21 patients (75%). After a mean follow-up of 20 months, 80.9% of these patients were recurrence free. The bladder preservation rate for the ablative group was 78.6%. CONCLUSIONS: Combined local bladder hyperthermia and intravesical chemotherapy has a beneficial prophylactic effect in patients with G3 superficial bladder cancer. Ablation of high-grade bladder tumors is feasible, achieving a complete response in about three quarters of the patients.

Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors.

PURPOSE: The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study. MATERIALS AND METHODS: A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system, based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas. RESULTS: After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved. CONCLUSIONS: Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.

Preliminary European results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder.

INTRODUCTION: Superficial bladder cancer can be treated by transurethral resection (TUR) and adjuvant intravesical therapy. Intravesical bacillus Calmette-Guérin (BCG) has been proven to be more efficacious with respect to recurrence prevention than intravesical chemotherapy, although at the cost of more severe side effects. There is a need for a new treatment modality with higher efficacy and less toxicity. The subject of this study is the efficacy of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Ninety eligible patients received adjuvant treatment with a combination of mitomycin-C (MMC) and local microwave hyperthermia. All patients had multiple or recurrent Ta or T1 TCC of the bladder and were classified as intermediate or high risk according to EAU criteria. In total, 41 patients were BCG failures. The treatment regimen included 6 to 8 weekly sessions followed by 4 to 6 monthly sessions. Follow-up consisted of video-cystoscopy and urine cytology every 3 months. All patients were observed for 2 years. RESULTS: Kaplan-Meier analyses of the total group (N = 90) indicated that 1 year after treatment only 14.3% (SE 4.5%) of all patients experienced a recurrence. After 2 years of follow-up the risk of recurrence was 24.6% (SE 5.9%). No progression in stage and grade was observed. CONCLUSION: Microwave induced hyperthermia combined with MMC has promising value in intermediate or high risk superficial bladder cancer patients compared to literature data of BCG and/or intravesical chemotherapy, particularly where other treatments, i.e. BCG, have failed.