LOCAL HYPERTHERMIA FOR PROSTATE CANCER C. SERVADIO, M.D. Z. LEIB, M.D.
From the Department of Urology, Beilinson Medical Center, Sackler School of Medicine, Tel Aviv University, Petah Tiqva, Israel
ABSTRACT--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 (4144 °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.
ts introduced by us some treatment for cancer of y clinical results in our :s have been reported. 1 experience, an entirely :al hyperthermia to the loped here. After exten:k, the equipment was :ed by three conditions: benign prostate enlargestatitis. 2-4 Herein we reries of cases of cancer of nd Methods used in this work and aental in developing 5-7 is Fhis equipment consists crowave generator (915 robe (antenna) through sated to 41 °-44 °C, (3) a ]evice in the antenna for rectal wall, (4) several ocated on the rectal wall ra for accurate positionCo., Rehovot, Israel.
~91 /
ing of the probe with respect to the heated prostate and c a r e f u l t e m p e r a t u r e - m o n i t o r i n g during the treatment, and (5) a computer for accurate programming of each treatment to fit individual prostatic size, for careful monitoring of each treatment within a preset temperature range, and for accurate monitoring and recording of all pertinent data. Treatments do not require any anesthesia; they are given on an outpatient basis, generally lasting for one hour, and are repeated for a total of six to ten times, once or twice a week. Forty-four patients with prostatic cancer are herein reported. Of these, 17 (group I) already had widespread disease (Stage D2) with severe local symptoms of obstruction and pain. The other 27 (group II) had a locally advanced disease and were considered unsuitable for radical surgery. M e a n age in the first group was seventy-seven years (64 to 88 years) and in the second group, seventy-one years (67 to 84 years). All group I patients had metastatic disease, and all had been undergoing various forms of c o n v e n t i o n a l e n d o c r i n e therapy, mostly orchieetomy, diethylstilbestrol (DES)/or cyproterone acetate, for a m e a n period of seventy-three months. They all had, among other complications, severe local obstructive
VOLUME XXXVIII, NUMBER 4
307
symptoms and pain. Thirteen were in complete r e t e n t i o n and n e e d e d p e r m a n e n t u r e t h r a l catheter. Thermotherapy in this first group was used to achieve local palliation and was given twice per week for three weeks. The 27 group II patients with locally advanced disease were offered hyperthermia in order to hopefully improve conventional therapeutic results in view of the known synergistic effects of thermotherapy with other forms of treatment, such as radiotherapy. Nineteen patients had been receiving conventional hormonal therapy for an average of thirty-eight months, and this treatment was not discontinued. All patients had severe local obstructive and irritative symptoms, 9 of them with permanent urethral catheter. The remaining 8 pat i e n t s of this s e c o n d g r o u p w e r e n e w l y diagnosed eases, also with severe local symptoms, and 5 were in complete retention. These were treated with full-dose radiotherapy (7,000 rad) but were given, in addition, local hyperthermia twice per week for five weeks. The twice-per-week thermotherapy session immediately followed the daily radiotherapy session. Results No appreciable complications due to the hyperthermia were seen in either group, and treatments were well tolerated. In the first group, the permanent catheter could be removed in 5 eases, and these patients were able to resume spontaneous voiding. In another 7 patients, a considerable objective improvement in flow was observed; in 6 a marked relief in local pelvic pain was obtained. Twelve patients eventually died of their metastatic disease with an average of fourteen months post hyperthermia. Five are still alive, still on hormonal therapy with their original metastatic disease, but with minimal local symptoms. Of the 19 group II patients (localized disease) who were on hormonal therapy and were given hyperthermia, the permanent urethral catheter could be completely removed in 4. There was a marked improvement in urine flow in another 4 and significant reduction in residual urine in 3 others. No progression of the disease was noted in any of these eases. Two patients died of nonrelated causes during the second year of followup. T h e 8 p a t i e n t s w h o w e r e given radiotherapy with hyperthermia also did well. The permanent catheter could be removed in 3 patients, and considerable relief in pelvic pain
308
was obtained in anoth, gression of the disease: Total follow-up in tl: eer eases being treated now in its fourth year. measured by transrec creased considerably ir Repeat biopsy specin showed no evidence o f examined. Con•
Many experimenta] strated the efficacy of itself and particularly for the treatment of ca1 technical problems invq clinical situation, have implementation. We h in developing an appar temperature of the prc safety, thus allowing its of cancer of the gland, palliation in metastat: bination with other a ment because of its sy~ ealized stage of the dis has turned o u t to be v, has been repeatedly u but more so for beni~ (BPH) and chronic prc cal improvement, n a l t in these clinical condit This report does not trol cases. R e g a r d i n g they all had advanced been receiving hormc time. Their definite could only be attribute mia. Moreover, 2 of thl a definite regression ot quent bone scans. Th some immunologic r( heat, as has already 1: mia studies. More res voted to this interestin the second group of 27 given in combination radiation, it is obvious] to attribute the good responses to the heat a some indications of thi low incidence of progi denee of negative bio] w i t h historical data
UROLOGY
/
OCTOBER
1991
/
. _
Department of Urology Beilinson Medical Center 49100 Petah Tiqva, Israel (DR. SERVADIO)
~s are now in progress to con[nary encouraging results. Eonclusions or local hyperthermia to the developed and used not only ltitis but also in cancer of the ,ur such cases are reviewed. .tastatic disease, and the heat • palliation of the 9.7 patients ,'ase, 19 received heat in additherapy, and 8 received heat iotherapy. A very marked resymptoms was obtained; the er could be removed in 12 of ation. Considerable improvew and reduction in residual 'd in another 11 cases. Relief ain was obtained in 9 of 15 i specimens were obtained in ith localized disease. Progreshis subgroup was seen only in studies will be needed to sub,~quivocal value of the Proproving the cure rate of local1 used in combination with :ms of treatment.
/
OCTOBER 1991
/
References i. Yerushalmi A, and Servadio C: Local hyperthermia for treahnent of carcinoma of the prostate: a preliminary report, Prostate 3:623 (1982). 2. Servadio C, Leib Z, and Lev A: Further observations on the use of local hyperthermia for the treatment of diseases of the prostate in man, Eur Urol 12:38 (1986). 3. Servadio C, Leib Z, and Lev A: Diseases of prostate treated by local microwave hyperthermia, Urology 30" 97 (1987). 4. Servadio C, et ah Further observations on the effect of local hyperthermia on benign enlargement of the prostate, Urology 6: 204 (1989). 5. Leib Z, Rothem A, Lev A, and Servadio C: Histological observation in the canine prostate treated by local microwave hyperthermia, Prostate 8 : 9 3 (1986). 6. Lev A: Heat profiles of 915 MHz skirt-type antenna, presented at 4th International Symposium on Hyperthermic Oncology, Aarhus, Denmark, 1984. 7. Servadio C, Leib Z, and Lev A: Local hyperthermia to canine prostate: an experimental study, presented at 4th International Symposium on Hyperthermic Oncology, Aarhus, Denmark, 1984. 8. Cavaliere R, et al: Selective heat sensitivity of cancer cells: biochemical and clinical studies, Cancer 20:1351 (1968). 9. Field SB, and Bleehen NM: Hyperthermia in the treatment of cancer, Cancer Treat Rev 6 : 6 3 (1979). 10. Overgaard J: Cancer Therapy by Hyperthermia and Radiation, Baltimore and Munich, Urban & Schwartzenberg, Inc., 1978, p 49. 11. Servadio C, et ah Local thermotherapy to the benign prostate: a one-year followup, Eur Urol 18:169 (1990).
VOLUME XXXVIII, NUMBER 4
309
From the Department of Urology, Beilinson Medical Center, Sackler School of Medicine, Tel Aviv University, Petah Tiqva, Israel
ABSTRACT--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 (4144 °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.
ts introduced by us some treatment for cancer of y clinical results in our :s have been reported. 1 experience, an entirely :al hyperthermia to the loped here. After exten:k, the equipment was :ed by three conditions: benign prostate enlargestatitis. 2-4 Herein we reries of cases of cancer of nd Methods used in this work and aental in developing 5-7 is Fhis equipment consists crowave generator (915 robe (antenna) through sated to 41 °-44 °C, (3) a ]evice in the antenna for rectal wall, (4) several ocated on the rectal wall ra for accurate positionCo., Rehovot, Israel.
~91 /
ing of the probe with respect to the heated prostate and c a r e f u l t e m p e r a t u r e - m o n i t o r i n g during the treatment, and (5) a computer for accurate programming of each treatment to fit individual prostatic size, for careful monitoring of each treatment within a preset temperature range, and for accurate monitoring and recording of all pertinent data. Treatments do not require any anesthesia; they are given on an outpatient basis, generally lasting for one hour, and are repeated for a total of six to ten times, once or twice a week. Forty-four patients with prostatic cancer are herein reported. Of these, 17 (group I) already had widespread disease (Stage D2) with severe local symptoms of obstruction and pain. The other 27 (group II) had a locally advanced disease and were considered unsuitable for radical surgery. M e a n age in the first group was seventy-seven years (64 to 88 years) and in the second group, seventy-one years (67 to 84 years). All group I patients had metastatic disease, and all had been undergoing various forms of c o n v e n t i o n a l e n d o c r i n e therapy, mostly orchieetomy, diethylstilbestrol (DES)/or cyproterone acetate, for a m e a n period of seventy-three months. They all had, among other complications, severe local obstructive
VOLUME XXXVIII, NUMBER 4
307
symptoms and pain. Thirteen were in complete r e t e n t i o n and n e e d e d p e r m a n e n t u r e t h r a l catheter. Thermotherapy in this first group was used to achieve local palliation and was given twice per week for three weeks. The 27 group II patients with locally advanced disease were offered hyperthermia in order to hopefully improve conventional therapeutic results in view of the known synergistic effects of thermotherapy with other forms of treatment, such as radiotherapy. Nineteen patients had been receiving conventional hormonal therapy for an average of thirty-eight months, and this treatment was not discontinued. All patients had severe local obstructive and irritative symptoms, 9 of them with permanent urethral catheter. The remaining 8 pat i e n t s of this s e c o n d g r o u p w e r e n e w l y diagnosed eases, also with severe local symptoms, and 5 were in complete retention. These were treated with full-dose radiotherapy (7,000 rad) but were given, in addition, local hyperthermia twice per week for five weeks. The twice-per-week thermotherapy session immediately followed the daily radiotherapy session. Results No appreciable complications due to the hyperthermia were seen in either group, and treatments were well tolerated. In the first group, the permanent catheter could be removed in 5 eases, and these patients were able to resume spontaneous voiding. In another 7 patients, a considerable objective improvement in flow was observed; in 6 a marked relief in local pelvic pain was obtained. Twelve patients eventually died of their metastatic disease with an average of fourteen months post hyperthermia. Five are still alive, still on hormonal therapy with their original metastatic disease, but with minimal local symptoms. Of the 19 group II patients (localized disease) who were on hormonal therapy and were given hyperthermia, the permanent urethral catheter could be completely removed in 4. There was a marked improvement in urine flow in another 4 and significant reduction in residual urine in 3 others. No progression of the disease was noted in any of these eases. Two patients died of nonrelated causes during the second year of followup. T h e 8 p a t i e n t s w h o w e r e given radiotherapy with hyperthermia also did well. The permanent catheter could be removed in 3 patients, and considerable relief in pelvic pain
308
was obtained in anoth, gression of the disease: Total follow-up in tl: eer eases being treated now in its fourth year. measured by transrec creased considerably ir Repeat biopsy specin showed no evidence o f examined. Con•
Many experimenta] strated the efficacy of itself and particularly for the treatment of ca1 technical problems invq clinical situation, have implementation. We h in developing an appar temperature of the prc safety, thus allowing its of cancer of the gland, palliation in metastat: bination with other a ment because of its sy~ ealized stage of the dis has turned o u t to be v, has been repeatedly u but more so for beni~ (BPH) and chronic prc cal improvement, n a l t in these clinical condit This report does not trol cases. R e g a r d i n g they all had advanced been receiving hormc time. Their definite could only be attribute mia. Moreover, 2 of thl a definite regression ot quent bone scans. Th some immunologic r( heat, as has already 1: mia studies. More res voted to this interestin the second group of 27 given in combination radiation, it is obvious] to attribute the good responses to the heat a some indications of thi low incidence of progi denee of negative bio] w i t h historical data
UROLOGY
/
OCTOBER
1991
/
. _
Department of Urology Beilinson Medical Center 49100 Petah Tiqva, Israel (DR. SERVADIO)
~s are now in progress to con[nary encouraging results. Eonclusions or local hyperthermia to the developed and used not only ltitis but also in cancer of the ,ur such cases are reviewed. .tastatic disease, and the heat • palliation of the 9.7 patients ,'ase, 19 received heat in additherapy, and 8 received heat iotherapy. A very marked resymptoms was obtained; the er could be removed in 12 of ation. Considerable improvew and reduction in residual 'd in another 11 cases. Relief ain was obtained in 9 of 15 i specimens were obtained in ith localized disease. Progreshis subgroup was seen only in studies will be needed to sub,~quivocal value of the Proproving the cure rate of local1 used in combination with :ms of treatment.
/
OCTOBER 1991
/
References i. Yerushalmi A, and Servadio C: Local hyperthermia for treahnent of carcinoma of the prostate: a preliminary report, Prostate 3:623 (1982). 2. Servadio C, Leib Z, and Lev A: Further observations on the use of local hyperthermia for the treatment of diseases of the prostate in man, Eur Urol 12:38 (1986). 3. Servadio C, Leib Z, and Lev A: Diseases of prostate treated by local microwave hyperthermia, Urology 30" 97 (1987). 4. Servadio C, et ah Further observations on the effect of local hyperthermia on benign enlargement of the prostate, Urology 6: 204 (1989). 5. Leib Z, Rothem A, Lev A, and Servadio C: Histological observation in the canine prostate treated by local microwave hyperthermia, Prostate 8 : 9 3 (1986). 6. Lev A: Heat profiles of 915 MHz skirt-type antenna, presented at 4th International Symposium on Hyperthermic Oncology, Aarhus, Denmark, 1984. 7. Servadio C, Leib Z, and Lev A: Local hyperthermia to canine prostate: an experimental study, presented at 4th International Symposium on Hyperthermic Oncology, Aarhus, Denmark, 1984. 8. Cavaliere R, et al: Selective heat sensitivity of cancer cells: biochemical and clinical studies, Cancer 20:1351 (1968). 9. Field SB, and Bleehen NM: Hyperthermia in the treatment of cancer, Cancer Treat Rev 6 : 6 3 (1979). 10. Overgaard J: Cancer Therapy by Hyperthermia and Radiation, Baltimore and Munich, Urban & Schwartzenberg, Inc., 1978, p 49. 11. Servadio C, et ah Local thermotherapy to the benign prostate: a one-year followup, Eur Urol 18:169 (1990).
VOLUME XXXVIII, NUMBER 4
309
